[REV. MED. CLIN.

CONDES - 2013; 24(5) 847-856]

TALLA BAJA: ENFOQUE DIAGNÓSTICO Y

BASES TERAPÉUTICAS
SHORT STATURE: DIAGNOSTIC APPROACH AND THERAPEUTIC BASIS

DRA. VERÓNICA MERICQ G. (1, 2), DRA. JEANNETTE LINARES M. (3), DR. JOEL RIQUELME R. (3)

1. Endocrinóloga Infantil, Instituto de Investigaciones Materno Infantil. Profesora Titular. Universidad de Chile.
2. Endocrinología infantil. Departamento Pediatría. Clínica Las Condes.
3. Becado de endocrinología infantil, Instituto de Investigaciones Materno Infantil. Universidad de Chile
(ambos autores contribuyeron en forma similar al artículo).

Email: [email protected]

RESUMEN indications and are not exempt from complications. A healthy

La talla baja es un motivo de consulta cada vez más frecuente lifestyle and a positive psychosocial environment, allow the
que el pediatra debe pesquisar. En la evaluación debe incluir child to develop their full genetic potential.
una historia clínica completa, examen físico con una correc-
ta evaluación auxiológica y un seguimiento adecuado de la Key words: Short stature, growth rate, growth hormone.
velocidad de crecimiento. De esta forma, los exámenes com-
plementarios irán orientados a confirmar una sospecha diag-
nóstica. A pesar de que la mayoría de los pacientes tendrá INTRODUCCIÓN
una talla baja idiopática o variante normal, en alrededor de La estatura es un parámetro auxiológico muy útil para determinar el
un 5% estaremos frente a patología. El enfoque terapéuti- estado de salud de un niño. En este sentido el restraso del crecimiento
co, debe estar siempre orientado a la causa. Existen terapias puede ser la manifestación más precoz de patologías congénitas y ad-
que pueden mejorar la estatura final pero tienen indicaciones quiridas.
precisas y no están exentas de complicaciones. Un estilo de
vida saludable y un ambiente psicosocial favorable, permiti- La estatura tiene una herencia multifactorial, modulada por la acción de
rán que el niño desarrolle al máximo su potencial genético. varias hormonas y factores de crecimiento que tienen un rol diferente
en la vida pre y postnatal. Se ve influida además por factores ambienta-
Palabras clave: Talla baja, velocidad de crecimiento, hormona les como la alimentación y un adecuado entorno afectivo y psicosocial.
de crecimiento. Todo lo anterior da cuenta de que el crecimiento longitudinal es un pro-
ceso continuo, pero no lineal, que se va modificando tanto en ganancia
absoluta como en velocidad en las distintas etapas de la vida (1). Así
SUMMARY por ejemplo en el primer año de vida se espera una ganancia promedio
Short stature is a complaint of increasing frequency in pediatrics. de longitud de 25 cm y de 12 cm en el segundo año. Talla baja se define
Given the diverse etiology of growth failure, the pediatrician como una longitud o estatura menor al percentil 3 o menor a -2 des-
must be able to make a correct assessment of the growth and viaciones estándar (DE) para la edad y sexo, respecto a la media de la
development of children, including a complete medical history, población de referencia (2).
physical examination and a proper auxiological assessment
with a carefully monitored of their growth rate. This way, any
further examination shall be designed to confirm a diagnostic EVALUACIÓN INICIAL DEL NIÑO CON TALLA BAJA
suspicion. Although most patients will have a idiopathic short El enfrentamiento inicial de un niño con talla baja debe considerar la
stature, in about 5% we will find pathology. The therapeutic evaluación de una serie de indicadores de crecimiento, que nos permi-
approach should always be oriented to the cause. There are tirán hacer una estimación aproximada de los cambios somáticos que
therapies that can improve the final height but have precise experimenta el paciente en el tiempo. Dentro de éstos cabe destacar:

Artículo recibido: 12-04-2013 847

Artículo aprobado para publicación: 24-07-2013
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1. Curva de crecimiento: es de vital importancia contar con curvas 5. Relación Peso/Talla: es importante evaluar la talla de un niño en el
de referencia poblacional actualizadas y aplicables a la realidad local. El contexto de su curva de peso. Así por ejemplo, aquel paciente en el cual
MINSAL ha sugerido que los niños chilenos se evalúen con las curvas de se comprometió primero el peso y luego la talla, orienta a una enferme-
la OMS, que establecen al lactante alimentado con leche materna como dad sistémica como causa del hipocrecimiento (enfermedades renales,
patrón de referencia para determinar el crecimiento adecuado hasta los cardíacas, pulmonares o malabsorción). Por el contrario, una talla baja
5 años (3). Luego se deben utilizar las curvas NCHS, recordando que és- asociada a un incremento de peso, hace necesario descartar una patolo-
tas representan a población norteamericana, de estrato socioeconómico gía endocrina, como déficit de hormona de crecimiento, hipotiroidismo,
medio y alto, alimentados con fórmula (4). hipercortisolismo, entre otras.

2. Medición de la estatura: respecto a la talla, las medidas deben

6. Talla diana o carga genética: la talla final de un niño tiene rela-
ser obtenidas en forma correcta, con el paciente descalzo y con instru-
ción directa con la estatura de sus padres, la cual debe ser medida por
mentos adecuados, usando un estadiómetro fijo a la pared con barra
el pediatra y no solo referida anamnésticamente. En el caso de evaluar
móvil en 90° y escala métrica, desde los dos años y con infantómetro
una niña, la carga genética se determina: [(talla padre-13 cm) + talla
(podómetro) para medición de talla en decúbito en lactantes. Recordar
madre]/2 y en el caso de los niños: [talla padre + (talla madre +13 cm)]/2.
que en la transición de medición en decúbito a evaluación de pie, no
Luego se grafica en la curva de crecimiento y se dibuja el rango de 1
debiera existir una diferencia mayor a 2 cm.
desviación estándar que para hombre corresponde a +/- 7 cm y en el
3. Talla absoluta. Una talla menor a -3 DE, debe considerarse siem- caso de las mujeres, a +/- 5 cm.
pre como patológica, mientras que la mayoría de los niños que crece
entre percentil 3 y 5, en general no tiene patología y corresponden
a variantes normales (talla baja familiar y/o retraso constitucional del
desarrollo). FIGURA 1. CURVA DE CRECIMIENTO NORMAL

4. Velocidad de crecimiento: expresada en cm/año, constituye uno

de los elementos críticos en la evaluación de un paciente con talla
baja. Una velocidad de crecimiento normal, es un buen y precoz indi-
cador de salud en un niño. Debe ser establecida en un período no me-
nor a 3 meses en el lactante y a 6 meses en el niño mayor (1). Hay que
considerar que en los primeros dos años de vida un sujeto adquiere el
carril de crecimiento que corresponde a su carga genética, por lo tan-
to, en ese período pueden ocurrir cambios en la curva de crecimiento
(canalización). Posteriormente y hasta el inicio del desarrollo puberal,
no es habitual cambiar de carril de crecimiento y siempre amerita eva-
luación. Cabe señalar que luego de los 2 años no debieran producirse
cambios en la curva de crecimiento >0,25DE/año (5). La velocidad de
crecimiento varía en las distintas etapas de la vida (ver tabla Nº1) y es
importante destacar que su valor mínimo se alcanza en edad escolar
previa al inicio puberal y no debe ser inferior a 4 cm/año.

TABLA 1. VELOCIDAD DE CRECIMIENTO SEGÚN

EDAD Y SEXO
EDAD CM/MES INTERVALO (CM/AÑO)

1º año 2 24-25

2º año 1 12-13

3º año 0,7 7-9

4-10 años 0,5 5-6

Prepuberal 0,3 3-4 Curva de crecimiento normal graficada en línea discontinua, discurre
entre percentiles 25-50 acorde a la talla media parental o talla diana
Pubertad 0,7 7-12 (TD). Sobre ésta se dibuja una línea vertical que representa ±1DE.

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Una vez establecido el diagnóstico de talla baja, se debe precisar su estatura, desarrollo psicomotor, encuesta y estado nutricional, desa-
causa, para lo cual se procederá a efectuar una exhaustiva anamnesis rrollo puberal, uso de fármacos y/o drogas, comorbilidades, hábitos de
y examen físico, junto con exámenes complementarios de laboratorio e vida, actividad deportiva, horas de descanso y el entorno social. Los
imágenes. De esta forma podremos catalogar las causas talla baja como antecedentes familiares son importantes ya que la herencia influye de
Idiopáticas (sin causa reconocible) o Patológicas, que a su vez pueden forma significativa en la talla, debiendo objetivarse la talla parental y
ser primarias (trastornos del crecimiento que afectan directamente al familiares directos (medir toda vez que sea posible), así como edad de
cartílago de crecimiento) o secundarias a condiciones ambientales o desarrollo puberal de ambos padres, edad de menarquia de la madre,
patología sistémica (ver tabla Nº2). consanguinidad y enfermedades familiares de posible carácter genético.

Anamnesis y Examen físico: El examen físico de un niño con talla baja debe incluir una detallada
En la anamnesis de un paciente con talla baja se deberá precisar an- evaluación auxiológica de peso (P), talla (T), relación P/T y proporcio-
tecedentes perinatales como enfermedades y noxas maternas durante nes corporales: circunferencia craneana, envergadura, talla sentado,
el embarazo, crecimiento intrauterino, edad gestacional, peso y talla al segmento superior (SS), segmento inferior (SI), relación SS/SI, distancia
nacer, posibles lesiones del parto, entre otras. En relación a los antece- acromion-olécranon, olécranon-radio. Todas estas medidas están estan-
dentes personales se debe consignar el tiempo de evolución de baja darizadas por edad y sexo para una población determinada. El SI corres-

TABLA 2. CAUSAS DE TALLA BAJA SEGÚN ESPE (EUROPEAN SOCIETY FOR PAEDIATRIC ENDOCRINOLOGY)

PRIMARIAS (alteración intrínsecas del cartílago de crecimiento)

1. Síndromes definidos 2. Pequeño para la 3. Displasias esqueléticas 4. Displasias con defectos de la

- Sd. Turner edad gestacional - Acondroplasia mineralización
- Sd. Noonan sin crecimiento
- Hipocondroplasia - Raquitismo
compensatorio.
- Sd. Down - Discondrosteosis
- Sd. de Digeorge - Osteogénesis imperfecta
- Sd. Cornelia de Lange - Mucopolisacaridosis
- Sd. de Silver-Russell

SECUNDARIAS (alteración de la fisiología del cartílago de crecimiento)

1. Desnutrición 3. Desórdenes del eje GH/IGF-1 y resistencia a GH 6. Psicosocial:

- Deprivación emocional
2. Enfermedades sistémicas: 4. Endocrinopatías - Anorexia nerviosa
- Cardiopatía - Sd. Cushing - Depresión
- Enfermedad pulmonar crónica - Hipotiroidismo
- Enfermedad hepática - Diabetes mellitus sin control metabólico 7. Iatrogénicas:
- Enfermedad intestinal - Glucocorticoides (local o
(malabsorción, enf. inflammatoria intestinal) 5. Enfermedades metabólicas: sistémico)
- Sd. intestino corto - Metabolismo Ca/P - Radio/Quimioterapia
- Enfermedad renal crónica - Errores innatos del metabolismo (carbohidratos,
- Anemia crónica lípidos, proteínas)

IDIOPÁTICA

1. Con/sin baja estatura familiar 2. Con/sin maduración lenta

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ponde a la distancia entre sínfisis pubiana y el suelo. El SS se obtiene me de Turner (cuello alado, cúbito valgo, implantación baja del cabe-
restando a la talla el SI. La relación SS/SI normalmente declina con la llo, coartación aórtica, malformaciones renales), Síndrome de Noonan
edad, alcanzando aproximadamente 1,7 en recién nacidos y 1 desde los (cuello corto, orientación antimongoloide de hendiduras palpebrales,
10 años hasta la vida adulta. La envergadura se mide con los brazos en estenosis pulmonar, malformaciones torácicas y esternales), Síndrome
extensión completa y abducción de 90º; en condiciones normales esta de Silver-Rusell (facie triangular, historia de restricción del crecimiento
medición es más corta que la estatura en pacientes prepuberales y luego intrauterino) (6). Otros síndromes genéticos asociados a talla baja se
de la pubertad, se hace ligeramente superior a la talla (1). detallan en la Tabla Nº3.

El estudio de proporciones corporales es de especial relevancia, ya que Estudio complementario

existen patologías que se caracterizan por un crecimiento disarmónico, El estudio complementario debe ser orientado según los hallazgos de
como es el caso de las displasias esqueléticas. Así por ejemplo, en las la anamnesis, examen físico y auxiológicos, con el fin de establecer un
acondroplasias e hipocondroplasias se observa un acortamiento rizomé- diagnóstico etiopatogénico (2).
lico de extremidades, mientras que la haploinsuficiencia del gen SHOX En aquellos pacientes con talla baja en los que la historia y examen
(short stature homeobox) se asocia a acortamiento mesomélico de las físico no orienten a una causa en particular, el pediatra debe solicitar
extremidades (Síndrome de Leri-Weill), ver figura Nº2. Por otro lado, exámenes generales que se detallan a continuación:
un paciente con talla baja proporcionada y una relación P/T normal a - Hemograma/VHS: la talla baja puede asociarse a anemia, talasemia,
aumentada puede asociarse a endocrinopatías como déficit de hormona sickle cell disease, infecciones subagudas y crónicas, enfermedad infla-
de crecimiento, hipotiroidismo o Síndrome de Cushing. Una talla baja matoria intestinal y otros procesos inflamatorios crónicos.
proporcionada con una relación P/T disminuida puede asociarse a pato- - Creatinina, electrolitos plasmáticos, Ca/P plasmático, gases venosos,
logías con un mayor gasto metabólico (cardiopatía, insuficiencia hepá- orina completa: la enfermedad renal crónica puede asociarse a talla
tica, insuficiencia renal) o malabsorción. Los signos carenciales de esta baja, incluso en ausencia de otros síntomas de enfermedad. En niños
última deben ser buscados activamente en el examen físico, así como < de 3 años con hipocrecimiento se debe tener presente la acidosis
también una adecuada evaluación del grado de desarrollo puberal. tubular renal como causa de hipocrecimiento de origen renal.
- Albúmina, glicemia, pruebas hepáticas: para descartar enfermedad
El examen físico segmentario debe buscar dismorfias y fenotipos que hepática.
orienten a algún síndrome genético asociado a talla baja, como Síndro- - IgA total, anticuerpos IgA antitransglutaminasa e IgA antiendomisio:
un 2-8% de los niños con talla baja sin síntomas gastrointestinales
tienen enfermedad celíaca. Este porcentaje puede aumentar a un 19-
FIGURA 2. 59% si las otras causas de talla baja han sido ya descartadas. Se debe
recordar que entre un 7-10% de los pacientes con enfermedad celíaca
tienen déficit de IgA, por lo que ésta debe ser siempre solicitada junto al
estudio serológico específico (5).
- Radiografía de Carpo: para determinación de edad ósea y, a través de
ésta, predicción de talla adulta. Debe ser solicitada a todos los pacientes
con talla baja. Además es útil para evaluar anormalidades óseas asocia-
das a Sd. Leri-Weill o a raquitismo.
- TSH y T4 libre: para descartar hipotiroidismo primario, dada su pre-
valencia en población general. En caso de estar alteradas, completar
estudio con anticuerpos antitiroideos (tiroiditis autoinmune) y, en caso
de existir bocio, con ecografía tiroidea.
- Parasitológico seriado de deposiciones: como causa de malabsorción
secundaria.
Existe una serie de exámenes de segunda línea, que pueden ser soli-
citados por el pediatra en caso de que el estudio inicial sea negativo,
aunque pueden ser pedidos desde el principio en caso de encontrar
hallazgos que ameriten su solicitud (5).
- Cariograma: en caso de dismorfias sugerentes de síndromes cromo-
sómicos asociados a talla baja. El diagnóstico de Síndrome de Turner
(prevalencia de 1:2000) debe ser considerado en toda niña con talla
Paciente de 17 años con Síndrome de Leri-Weill. Talla final de 132 cm. baja sin causa aparente. En varones con talla baja debe solicitarse si
Nótese el acortamiento mesomiélico de extremidades superiores e infe- ésta se asocia a anomalías genitales, retraso del desarrollo psicomotor
riores (A) y la deformidad de Madelung del antebrazo derecho (B). o RCIU severo sin crecimiento compensatorio posterior.

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TABLA 3. SÍNDROME CLÍNICOS ASOCIADOS A TALLA BAJA

SÍNDROME DISMORFIAS GEN/LOCUS HERENCIA

Deleción 18q Microcefalia, hipertelorismo, ptosis, estrabismo, orejas grandes, retardo 18q Esp
mental, micropene

Bloom Telangiectasias, voz aguda, manchas café con leche, hipogonadismo, RECQL3 AR
inmunodeficiencia

Cockayne Microcefalia, fotosensibilidad, retardo mental, lipoatrofia, microftalmia ERCC6, ERCC8 AR

Coffin-Lowry Sordera, deformidad esquelética progresiva, labios y glabela prominentes RPS6KA3 RLX

Cornelia de Lange Sinofris, hirsutismo, oligodactilia, narinas antevertidas, micrognatia NIPBL, SMC1L1, SMC3 AD, RLX, Esp

DiGeorge Anomalías palatinas, cardiopatías conotruncales 22q11.2 Esp

Down Epicanto prominente, hipotonía muscular, macroglosia 21 Esp

Dubowitz Retardo mental, microcefalia, eczema, frente amplia Desconocido

Floating harbor Cara triangular, nariz bulbosa y ancha, enoftalmo, pestañas largas, voz Desconocido Esp
nasal, retraso del lenguaje++

Kabuki Fisuras palpebrales grandes, eversión tercio lateral párpado inferior, Desconocido Esp, AD
puente nasal ancho, cejas arqueadas, orejas grandes y dismórficas

Langer-Geidion Orejas en coliflor, cabello escaso, filtrum largo, nariz bulbosa, exostosis CUL7 AR
ósea

Noonan Hipertelorismo, fisuras palpebrales de orientación antimongoloide, PTPN11, RAF1, KRAS, SOS1 AD
criptorquídea, cuello alado

Prader-Willi Criptorquídea, micropene, hipotonía muscular, manos y pies pequeños 15q11-q13 Esp

Neurofibromatosis tipo 1 Manchas café con leche, neurofibromas cutáneos, nódulos de Lisch NF1 AD

Rubinstein-Taybi Pulgares y ortejos anchos, criptorquídea 16p13.3, CREBBP, EP3000 AD, Esp

Silver-Rusell Hemihipertrofia, compromiso de peso, circunferencia craneana normal, DUP7 Esp

cara pequeña triangular, clinodactilia

Seckel Cara de pájaro, microcefalia severa PCNT AR

Leri-Weill (SHOX) Deformidad de Madelung Xp22.3 AD

Turner (45,X) Aorta bicúspide, coartación aórtica, cúbito valgo, mamilas hipoplásicas, X Esp
linfedema congénito, nevos múltiples, onicodisplasia, cuello alado

Esp: esporádica; RLX: recesiva ligado al X; AD: autosómica dominante; AR:autosómica recesiva.

- Estudio de eje Somatotropo: el déficit de hormona de crecimiento (GH) de IGF-1 aumentan progresivamente con la pubertad, deben ser siempre
tiene una prevalencia de 1:2500-1:6000. Dado que la GH circulante se correlacionados con el grado de maduración ósea, más que con la edad
secreta en peaks durante el día, su determinación en condiciones basa- cronológica (7). Si los valores de IGF-1 y/o IGFBP-3 están bajos, se sugiere
les no es de utilidad cuando se sospecha deficiencia. Su estudio se basa efectuar una prueba de estimulación de GH con clonidina o insulina. Ésta
en la determinación de niveles plasmáticos de factores de crecimiento solo debe ser indicada por el especialista. Si a pesar de la estimulación los
de síntesis hepática (o de sus proteínas transportadoras), dependientes niveles de GH son menores de 5ng/ml (medidos por ICMA), es altamente
de hormona de crecimiento. Así se puede medir IGF-1 e IGFBP-3. Debe probable el diagnóstico de déficit de hormona de crecimiento.
recordarse que los niveles de IGF-1 son dependientes de la GH, pero - Radiografía de esqueleto: debe solicitarse siempre dentro del es-
también del estado nutricional y la función hepática. Como los valores tudio de un paciente con talla baja desproporcionada con el fin de des-

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cartar una displasia esquelética (8). El estudio radiológico debe incluir Talla Baja Idiopática
cráneo (proyección PA y lateral), columna total (AP y lateral), tórax (AP), Se define como una condición en la cual la talla de un individuo está
pelvis (AP), huesos largos (1 brazo y 1 pierna AP), mano izquierda (PA). bajo 2 desviaciones estándar para su edad, sexo y población, sin evi-
Algunos de los hallazgos posibles de encontrar son craneosinostosis, dencia de alteraciones sistémicas, nutricionales, endocrinas o cromosó-
platispondilia (en osteogénesis imperfecta), el estrechamiento de la dis- micas. Tienen un peso y talla de nacimiento normal y no son deficientes
tancia interpeduncular caudal de la columna (en la hipocondroplasia), de hormona de crecimiento (9).
retraso de osificación de huesos púbicos (condrodistrofia neonatal), la
deformidad de Madelung (incurvamiento del radio y subluxación cubital Los varones, independientemente de su clase social, perciben una mayor
distal observada en la discondrosteosis de Leri-Weill), entre otras (ver desventaja de su talla baja en comparación con las mujeres; se ha des-
figura Nº2). crito además como factor de riesgo para problemas psicosociales como
- Neuroimagen: RNM cerebral solo en caso de sospecha de lesión infantilización, baja autoestima y bullying, especialmente aquellos que
intracraneana, defectos de línea media, déficit de GH o hipopituitarismo. son derivados al especialista. Se estima que entre el 60 a 80% de todos
los niños con talla <-2 DE, serán catalogados como talla baja idiopática
(TBI). Esta definición incluye a los pacientes con talla baja familiar y
ORIENTACIÓN DIAGNÓSTICA retraso constitucional del crecimiento y desarrollo, antiguamente cata-
Una vez es evaluada la curva de crecimiento, la antropometría, la talla logadas como variantes de normalidad (10).
diana (carga genética), la historia familiar y la edad ósea, será posible
orientar el estudio etiológico en la mayoría de los pacientes con talla baja La talla baja familiar se caracteriza por una talla bajo el percentil 3,
(1). A continuación se detalla un algoritmo de evaluación (ver figura Nº3). pero con un crecimiento y desarrollo a una velocidad normal, edad ósea

FIGURA 3. ALGORITMO DE EVALUACIÓN INICIAL DEL PACIENTE CON TALLA BAJA

Talla baja

Proporcionada Desproporcionada

Prenatal Postnatal Displasia ósea, raquitismo,

mucopolisacaridosis,
cromosomopatías

RCIU
Sd. dismórficos V crecimiento N V crecimiento
Sd. cromosómicos

Edad ósea N Edad ósea P/T P/T

retrasada

Antecedente Antecedente Enfermedad Endocrinopatía

de baja talla de retraso sistémica Déficit GH
familiar constitucional Desnutrición Hipotiroidismo
Malabsorción Sd. Cushing

Talla baja Retraso

familiar constitucional
del crecimiento

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dentro de límites normales y una estatura acorde a la talla parental. bajo la talla parental. La talla adulta de los niños con TBI generalmente
Recordar siempre medir a los padres y sus proporciones corporales, ya será menor que su talla diana (9). Además se deben clasificar por la pre-
que un padre con talla baja severa, podría corresponder a una displasia sencia o ausencia de retraso de la edad ósea, que indicará la posibilidad
esquelética, como la hipocondroplasia o un síndrome de Leri-Weill, que de un retraso de su crecimiento y desarrollo. Estos elementos, junto a la
son de herencia autosómico dominante. predicción de talla adulta y la severidad de la baja estatura, deben ser
considerados al momento de decidir iniciar un tratamiento.
El retraso constitucional del crecimiento y desarrollo, se caracteriza por
una maduración física lenta. Tienen peso y talla de nacimiento normales, Pequeño Para la Edad Gestacional (PEG)
pero su velocidad de crecimiento cae en algún momento de la infancia. Se define como un peso y/o talla de nacimiento menor a -2DE para
Su edad ósea está atrasada >2 DE y progresa lentamente. Inician su una población determinada. Requiere de datos referenciales de peso y
pubertad en forma tardía y hasta el 90% tienen el antecedente de de- longitud en una población y etnia determinadas. La Sociedad Chilena
sarrollo puberal tardío en los padres o familiares. En general tienen un de Pediatría, recomienda utilizar las curvas Alarcón-Pittaluga. Cerca del
buen pronóstico de talla final, ya que crecen por tiempo más prolongado 90% de los pequeños para edad gestacional logrará un crecimiento
(ver figura Nº4). compensatorio, el patrón de éste muestra un incremento en la velocidad
de crecimiento los primeros 2 a 3 años de vida, seguido por una talla es-
Respecto al enfrentamiento, la principal distinción es entre aquellos table en la infancia, una edad normal de inicio puberal y una talla adulta
niños con historia de talla baja familiar, cuya talla está dentro de lo menor a su carga genética (11). Aquellos sin crecimiento dentro de los
esperado para su carga genética y aquellos niños cuya estatura está primeros 6 meses de vida requieren una mayor evaluación y aquellos

FIGURA 4. CURVA DE CRECIMIENTO

(A) Talla baja familiar: Talla <p3, con velocidad de crecimiento normal, sin retraso de la edad ósea y curva de crecimiento acorde a talla diana (TD). (B) Retraso consti-
tucional del crecimiento: Talla <p3, curva de crecimiento por debajo del percentil de la talla diana, con retraso de la edad ósea (x) y talla final acorde a carga genética.

853
 [REV. MED. CLIN. CONDES - 2013; 24(5) 847-856]

que se mantengan bajo -2DE a los 2 años, son candidatos a tratamiento

con hormona de crecimiento. TABLA 4. CARACTERÍSTICAS CLÍNICAS DEL NIÑO
CON DÉFICIT DE GH
Endocrinopatías
Aunque en la mayoría de los casos el paciente con talla baja tendrá - Talla baja proporcionada.
una variante de la normalidad, aproximadamente un 5% tendrá una - Velocidad de crecimiento disminuida.
patología que cause su baja estatura. En el crecimiento postnatal el eje
- Facie: frente amplia, acentuada prominencia frontal y occipital,
hormonal más importante es el de la hormona de crecimiento, influyen
hipoplasia de macizo facial, nariz cóncava, mejillas redondeadas,
también otros sistemas hormonales, como las hormonas tiroideas, el
boca pequeña, mentón poco desarrollado.
cortisol y los esteroides sexuales. Dentro de las endocrinopatías cabe
mencionar: - Voz aguda.

- Hipoglicemia.
- Déficit de hormona de crecimiento: puede presentarse en cual-
- Micropene.
quier momento de la vida, si es congénito, el recién nacido puede pre-
sentar hipoglicemia asociada o no a ictericia prolongada, micropene, - Distribución troncal de grasa corporal.
defectos de línea media, criptorquidea y una fascie característica (ver - Índice Peso/Talla normal o alto.
tabla Nº4 y figura Nº5) (2). La mayoría presenta peso y talla de na-
- Retraso de la maduración ósea.
cimiento normal y la velocidad de crecimiento cae después de los 6
meses de vida. Si es adquirido, el único signo puede ser una caída en la - Pubertad retrasada.
velocidad de crecimiento, seguido de talla baja asociado a un aumento - Pruebas de estimulación con respuesta <5ng/ml (ICMA).
de peso concomitante. Esto último siempre debe ser un signo de alarma,
- Posible asociación a otros déficit hormonales.
ya que lo esperable en un paciente con sobrepeso es que tenga una

FIGURA 5. DEFICIT DE HORMONA DEL CRECIMIENTO (GH)

854
 [TALLA BAJA: ENFOQUE DIAGNÓSTICO Y BASES TERAPÉUTICAS - DRA. VERÓNICA MERICQ G. Y COLS.]

talla normal o que aumente su velocidad de crecimiento secundario al Los usos aprobados actualmente por la Food and Drug Administration
avance de edad ósea que se produce con el aumento de los estrógenos (FDA) se enumeran en la tabla Nº 5.
provenientes de su aromatización en el tejido adiposo. En la historia
siempre se debe indagar por traumatismo o infección del sistema ner-
vioso central, irradiación craneal y síntomas de tumor como cefalea y
TABLA 5. INDICACIONES APROBADAS POR LA FDA
alteraciones visuales. PARA EL USO DE HORMONA DE CRECIMIENTO

- Hipotiroidismo: en las formas adquiridas, los pacientes en gene- - Déficit de hormona de crecimiento.
ral son normales al examen físico. Pueden presentar un retraso en su - Síndrome de Turner.
crecimiento y en su edad ósea, y la caída de la talla ser el único signo.
- Síndrome de Prader Willi.
Respecto a los síntomas, se debe preguntar por crecimiento de fanéreos,
sequedad de la piel, constipación, intolerancia al frío, desánimo y alte- - Insuficiencia renal crónica.
raciones menstruales. - Síndrome de Noonan.

- Hipogonadismo: más frecuente en varones, son pacientes que llega- - Síndrome de Leri Weill.
da la adolescencia tienen una pubertad ausente (ausencia de caracteres - Talla baja idiopática (T<-2,25 DE).
sexuales a los 13 años en la niña y 14 años en el niño) o incompleta,
- Pacientes pequeños para edad gestacional sin crecimiento
por lo que no presentan estirón puberal, siendo éste generalmente el
compensatorio, después de los primeros dos años de vida.
motivo de consulta. Pueden tener historia de micropene o criptorquidia.

- Hipercortisolismo: la mayoría de las veces será iatrogénico, el sín- El objetivo del tratamiento es normalizar la talla durante la niñez, de-
drome de Cushing de causa orgánica es muy raro. Las manifestaciones
biendo estar centrado en el interés del paciente. Lograr una talla adulta
clínicas independiente de la causa son: cara de luna, relleno temporal,
lo más cercana a lo normal para su población, que le permita una ade-
giba dorsal, acné, hirsutismo, estrías violáceas, HTA, hiperglicemia y talla
cuada adaptación social y evitar las eventuales consecuencias psicoló-
baja asociada obesidad centrípeta, siendo estos dos últimos, los signos
gicas negativas derivadas de la baja estatura. Requiere monitorización
más sensibles (2).
clínica y bioquímica periódica por el endocrinólogo infantil y debe man-
tenerse hasta que el paciente alcance su talla final, es decir, cuando se
han fusionado los cartílagos de crecimiento o la velocidad de crecimien-
¿CUÁNDO DERIVAR AL ENDOCRINÓLOGO?
to es menor a 2 cm/año.
Deben ser derivados para evaluación por endocrinólogo infantil aquellos
pacientes que presenten alguno de los siguientes criterios (5):
- Talla/Edad <-3DE. En EE.UU. ha sido aprobado el uso de GH en talla baja idiopática cuan-
- Talla/Edad en repetidos controles <-2,5DE. do la estatura en <-2,25 DE. El tratamiento puede llegar a mejorar mo-
- Diferencia entre carga genética y talla actual >2DE. destamente el pronóstico de talla adulta (entre 3 a 7 cm), y la velocidad
- Velocidad de crecimiento <4cm/año a cualquier edad. de crecimiento en 1cm/año. La magnitud del incremento se verá influen-
- Caída sostenida de percentiles de talla luego de los 18-24 meses de ciada por factores como la edad de inicio del tratamiento, la edad ósea
edad (cambios >1DE). y por la talla media parental (7).
- Talla baja asociada a desproporción o dismorfias.
- Pequeño para la edad gestacional (PEG) sin crecimiento compensatorio. El tratamiento con GH es, en general, bien tolerado y seguro, pero cos-
toso. Dentro de sus complicaciones se describen lipodistrofia en el sitio
de punción, aumento de nevus, hipertensión intracraneana benigna,
ENFOQUE TERAPÉUTICO ginecomastia prepuberal, artralgias, edema, hipotiroidismo transitorio,
El enfoque terapéutico del paciente con talla baja debe estar orientado hiperglicemia e intolerancia a la glucosa. La asociación entre el trata-
a su causa y debe ser siempre concensuado con el paciente y su familia. miento con hormona de crecimiento y malignidad no se ha demostrado.
El tratamiento puede incluir el uso de hormona de crecimiento, andró- Otro tratamiento utilizado para mejorar el crecimiento lineal en pacien-
genos e inhibidores de la aromatasa entre otros (7). tes peripuberales es la Oxandrolona, andrógeno poco potente a bajas
dosis (1,25 a 2,5 mg/día), de relativo bajo costo e incremento de la
El tratamiento con hormona de crecimiento está disponible hace más velocidad de crecimiento en 3 a 5 cm/año. Debe ser usada idealmente
de cinco décadas, y como hormona recombinante humana, creada por con edad ósea <11 años.
bioingeniería genética, desde 1985. Es un tratamiento inyectable, de
uso diario y de alto costo; no exento de complicaciones. La evidencia Los inhibidores de la aromatasa reducen la producción de estrógenos y
de sus resultados con estatura final en las diferentes patologías y de retrasan la maduración ósea, porque han sido utilizados en niños para
sus efectos adversos a largo plazo, es aún limitada (12). prolongar el crecimiento puberal e incrementar la talla, sin embargo han

855
 [REV. MED. CLIN. CONDES - 2013; 24(5) 847-856]

demostrado ser menos efectivos que los andrógenos. Su uso prolonga- rada solo en aquellos casos con fuerte sospecha de su deficiencia, par-
do puede asociarse a deformidades vertebrales, debido a la deficiencia ticularmente en pacientes con malabsorción y/o desnutrición severa.
estrogénica relativa, durante el crecimiento puberal (7).
SÍNTESIS
El Zinc es un oligoelemento esencial para el crecimiento somático en El éxito del tratamiento del hipocrecimiento dependerá del diagnóstico
niños, sin embargo, su deficiencia en rangos moderados a severos es precoz de la patología específica que lo causa. Frente a los pacientes
inusual incluso en países subdesarrollados. Por otro lado la prevalen- con variantes de la normalidad, se debe recomendar siempre una ade-
cia de la deficiencia de Zinc en países occidentales es desconocida, cuada alimentación y un estilo de vida saludable que incluya deporte y
pero se presume que sería baja (5). Por lo tanto su suplementación un adecuado hábito de sueño. Los pacientes con significativa desacele-
como parte del manejo de un paciente con talla baja debe ser conside- ración del crecimiento deben ser derivados al especialista.

REFERENCIAS BIBLIOGRÁFICAS

1. Cassorla F, Eyzaguirre F, Gaete X. Clasificación y valoración de la talla baja. Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the
Tratado de endocrinolocía pediátrica. Cuarta Edición. Pombo M (editor). 2009; European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol
174-180. Metab, November 2008, 93(11):4210–4217.
2. M Pombo, L Castro-Feijóo, P Cabanas Rodríguez. El niño con talla baja. 10. J. M. Wit et al. Idiopathic short stature: Definition, epidemiology and
Protoc diagn ter pediatr. 2011:1:236-54. diagnostic evaluation. Growth Hormone & IGF Research 18 (2008) 89–110.
3. http://www.cdc.gov/growthcharts. 11. Wit CC, Sas TC, Wit JM, Cutfield WS. Patterns of catch-up growth. J Pediatr.
4. http://www.who.int/childgrowth/standards/curvas_por_indicadores. 2013 Feb;162(2):415-20.
5. Wilma Oostdijk et al Diagnostic Approach in Children with Short Stature. 12. J. M. Wit et al. Idiopathic short stature: Management and growth hormone
Horm Res 2009;72:206–217. treatment. Growth Hormone & IGF Research 18 (2008) 111–135.
6. J.M. Wit et al. Genetic evaluation of short stature. Best Practice & Research 13. J.M. Wit. Introduction: Unresolved Issues in the Management of Children
Clinical Endocrinology & Metabolism 25 (2011) 1–17. with Idiopathic Short Stature. Horm Res 2009;71(suppl 1):68–69.
7. David B. Allen, Leona Cuttler. Short Stature in Childhood - Challenges and
Choices. N Engl J Med 2013;368:1220-8.
8. Kant SG et al. Radiographic evaluation of children with growth disorders.
Horm Res. 2007;68(6):310-5.
9. J de Cohen P. et al. Consensus Statement on the Diagnosis and Treatment Los autores declaran no tener conflictos de interés, relacionados
a este artículo.
of Children with Idiopathic Short Stature: A Summary of the Growth Hormone

856
Endocrinol Diabetes Nutr. 2017;64(S1):15---22

Endocrinología, Diabetes y Nutrición

www.elsevier.es/endo

DOCUMENTO DE CONSENSO

Prevención, diagnóstico y tratamiento de la obesidad.

Posicionamiento de la Sociedad Española para el
Estudio de la Obesidad de 2016!
Prevention, diagnosis, and treatment of obesity. 2016 position statement
of the Spanish Society for the Study of Obesity

Albert Lecube a,∗,1 , Susana Monereo b,1 , Miguel Ángel Rubio c ,

Purificación Martínez-de-Icaya d , Amelia Martí e , Javier Salvador f , Lluís Masmiquel g ,
Alberto Goday h , Diego Bellido i , Empar Lurbe j , José Manuel García-Almeida k ,
Francisco José Tinahones l , Pedro Pablo García-Luna m , Enrique Palacio n ,
Manuel Gargallo ñ , Irene Bretón b , Salvador Morales-Conde o , Assumpta Caixàs p ,
Edelmiro Menéndez q , Manel Puig-Domingo r y Felipe F. Casanueva s

a
Servicio de Endocrinología y Nutrición, Unidad de Obesidad, Hospital Universitari Arnau de Vilanova de Lleida, Institut de
Recerca Biomèdica de Lleida, CIBERDEM (CIBER de Diabetes y Enfermedades Metabólicas Asociadas, ISCIII), Universitat de Lleida,
Lleida, España
b
Servicio de Endocrinología y Nutrición, Hospital General Universitario Gregorio Marañón, Madrid, España
c
Servicio de Endocrinología y Nutrición, Hospital Clínico San Carlos, Madrid, España
d
Sección de Endocrinología y Nurición, Hospital Universitario Severo Ochoa de Leganés, Madrid, España
e
Departamento de Ciencias de la Alimentación y Fisiología, Universidad de Navarra, CIBERobn (CIBER de Fisiopatología de la
Obesidad y Nutrición, ISCIII), Instituto de Investigación Sanitaria de Navarra (Idisna), Pamplona, España
f
Departamento de Endocrinología y Nutrición, Clínica Universidad de Navarra, CIBERobn (CIBER de Fisiopatología de la Obesidad
y Nutrición, ISCIII), Instituto de Investigación Sanitaria de Navarra (Idisna), Pamplona, España
g
Servicio de Endocrinología y Nutrición, Unidad de Obesidad, Hospital de Son Llàtzer, Institut Universitari d’Investigació en
Ciències de la Salut (IUNICS-IdISPa), Universitat de les Illes Balears, Palma de Mallorca, España
h
Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), CIBERobn (CIBER de Fisiopatología de la Obesidad
y Nutrición, ISCIII), Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, España
i
Servicio Endocrinología y Nutrición, Complejo Hospitalario Universitario de Ferrol (CHUF), SERGAS, Ferrol, A Coruña, España
j
Departamento de Pediatría, Consorcio Hospital General. CIBERobn (CIBER de Fisiopatología de la Obesidad y Nutrición, ISCIII),
Universidad de Valencia, Valencia, España
k
Complejo Hospitalario de Málaga (Virgen de la Victoria), Hospital Quirón-Salud Málaga, Universidad de Málaga, Málaga, España
l
Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clínico
Virgen de la Victoria, CIBERobn (CIBER de Fisiopatología de la Obesidad y Nutrición, ISCIII), Universidad de Málaga, Málaga, España
! Este documento ha recibido la aprobación de las juntas directivas de la Sociedad Española de Endocrinología y Nutrición y de la Sociedad

Española de Diabetes. La versión completa puede encontrase en la página Web de ambas sociedades (www.see.es; www.sediabetes.org),
así como en la de la Sociedad Española para el Estudio de la Obesidad (www.seedo.es).
∗ Autor para correspondencia.

Correo electrónico: [email protected] (A. Lecube).

1 Comparten primer autor.

http://dx.doi.org/10.1016/j.endonu.2016.07.002
1575-0922/© 2016 SEEN. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
16 A. Lecube et al.

m
Unidad de Nutrición Clínica y Dietética, Servicio de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla,
España
n
Servicio de Endocrinología y Nutrición, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife,
España
ñ
Servicio de Endocrinología y Nutrición, Hospital Virgen de la Torre, Madrid, España
o
Unidad de Innovación Cirugía Mínima Invasiva, Servicio de Cirugía General y Digestiva, Hospital Universitario Virgen del Rocío,
Sevilla, España
p
Servicio de Endocrinología y Nutrición, Hospital Universitari Parc Taulí de Sabadell, Corporació Sanitària Parc Taulí, Institut de
Recerca I3PT, Universitat Autònoma de Barcelona, Sabadell, España
q
Servicio de Endocrinología y Nutrición, Hospital Universitario Central de Asturias (HUCA). Departamento de Medicina,
Universidad de Oviedo, Oviedo, España
r
Servicio de Endocrinología y Nutrición, Hospital Germans Trias i Pujol, Badalona. Departamento de Medicina, Universidad
Autónoma de Barcelona, Barcelona, España
s
Departamento de Medicina, Universidad de Santiago, Compejo Hospitalario Universitario de Santiago (CHUS), CIBERobn (CIBER
de Fisiopatología de la Obesidad y Nutrición, ISCIII), Santiago de Compostela, España

Disponible en Internet el 16 de agosto de 2016

PALABRAS CLAVE
Obesidad;
Prevención;
Tratamiento;
Diagnóstico;
Comorbilidades;
Sociedad Española
para el Estudio de la
Obesidad

KEYWORDS
Obesity;
Prevention;
Treatment;
Diagnosis;
Comorbidities;
Spanish Society for
the Study of Obesity

Este posicionamiento surge con el objetivo de consolidar Actividad

física
la obesidad como enfermedad, una de las más prevalen- Nutrición Edad
tes e infravaloradas, menos diagnosticadas y tratadas de la menopausia

historia1 . Factores
genéticos Sueño
Ingesta-Gasto
Disruptores
Enfermedad
Etiopatogenia: elementos clásicos y nuevos endocrinos
psiquiátrica
protagonistas
Fármacos Obesidad Estrés
Entre los elementos clásicos encontramos la edad (sarco-
Factores
penia y mayor masa grasa en mayores de 65 años), el prenatales Factores
sexo (declive de hormonas anabólicas y estrógenos tras socioeconómicos

la menopausia), la genética (múltiples variantes génicas Microbiota

Alteraciones
Ambientes
intestinal obesogénicos
implicadas, pero con influencia aislada), el sedentarismo, hormonales
el comportamiento alimentario (interacción entre factores
biológicos y emocionales), determinados fármacos (antidia- Figura 1 La obesidad como enfermedad multifactorial.
béticos, anticonceptivos, antihistamínicos y psicotropos), la Remarcando la complejidad de la enfermedad, también
disfunción hipotálamo-hipofisaria y algunas enfermedades participan en su desarrollo la cronodisrupción (desfase hora-
endocrinas2---5 (fig. 1). rio, cambios del ciclo sueño-vigilia y privación de sueño), la
Prevención, diagnóstico y tratamiento de la obesidad. Posicionamiento SEEDO 2016 17

epigenética y programación fetal (desnutrición y sobreali- arterial (HTA) es un 25-40% más frecuente en el obeso que en
mentación materna, incluso en el periodo preconcepcional), la población general, implicando en su desarrollo la mayor
la enfermedad psiquiátrica (independientemente del tra- activación simpática y del sistema renina-angiotensina-
tamiento), el estrés (tanto crónico como incontrolado), la aldosterona. La obesidad es responsable del 44% de la carga
microbiota intestinal (predominio de firmicutes sobre bac- de diabetes mellitus tipo 2 (DM2), donde la prevalencia de
teroidetes, una microbiota poco diversa), los disruptores obesidad es del doble que en la población general.
endocrinos (bisfenol A, ftalatos, pesticidas e insecticidas),
el patrón alimentario (exceso de grasas y azúcares refinados,
consumo insuficiente de frutas y verduras), un estatus Obesidad y nuevas comorbilidades
socioeconómico desfavorecido y un ambiente obesogénico
(dispersión urbana, disponibilidad de comida. . .)6---9 . La obesidad es causa prevenible de cáncer de colon y recto,
de mama en mujeres posmenopáusicas, de endometrio,
¿Cómo y cuándo se diagnostica? riñón, esófago y páncreas16 . Es el principal factor de riesgo
para el síndrome de apnea hipoapnea del sueño. Incrementa
La obesidad se define por un porcentaje de masa grasa (MG) un 25% la posibilidad de sufrir trastornos del estado de ánimo
superior al 25% en hombres y al 33% en mujeres. Cuando y ansiedad. La prevalencia de la enfermedad hepática no
no podemos medir la MG utilizamos el IMC (obesidad leve o alcohólica por depósito de grasa alcanza el 100% en suje-
clase i [30-34,9 kg/m2 ], moderada o clase ii [35-39,9 kg/m2 ] tos con obesidad mórbida17 . Además, se asocia a artrosis de
y grave, mórbida o clase iii [≥ 40 kg/m2 ]), o el perímetro cadera y rodilla, pero también de articulaciones no de carga
de cintura (PC) (obesidad abdominal [≥ 102 cm en hombres, como las manos.
≥ 88 cm en mujeres; en bipedestación y sobre la cresta
ilíaca]). El IMC no informa de la distribución de la grasa
corporal, no diferencia entre masa magra (MM) y MG, y es un Beneficios de la pérdida ponderal
mal indicador en sujetos de baja estatura, edad avanzada,
musculados, con retención hidrosalina o gestantes10 . No se Junto a cambios en el estilo de vida, perder un 5-10%
considera útil medir el PC cuando el IMC ≥ 35 kg/m2 . del peso reduce hasta un 1,0% la HbA1c y las necesida-
La SEEDO promueve el uso de clasificaciones de obesidad des farmacológicas para la diabetes, así como la presión
que unen descriptores antropométricos y clínicos11 , así como arterial sistólica y diastólica, y el uso de tratamiento
fórmulas matemáticas desarrolladas en población española antihipertensivo18 . Incrementa la sensación de bienestar y
para estimar el porcentaje de MG (Clínica Universidad de la capacidad funcional. Pérdidas moderadas, del 3-5%, ya
Navarra-Body Adiposity Estimator)12 . producirán beneficios. Perder entre 2,5 y 5,5 kg de peso tras
2 años reduce el riesgo de DM2 un 30-60%.
Tras cirugía bariátrica existe una reducción de eventos
Epidemiología en España cardiovasculares mortales y no mortales, con resultados
favorables en mortalidad global, diabetes, factores de riesgo
Según el IMC la prevalencia es del 21,6% (22,8% varones,
cardiovascular, cáncer, síndrome de apnea hipoapnea del
20,5% mujeres), aumentando con la edad, y siendo mayor en
sueño, dolor articular y calidad de vida19 .
mujeres a partir de los 50 años; mayor en el Principado de
Asturias (25,7%) y menor en Islas Baleares (10,5%)13 . Según
el PC la obesidad abdominal es del 36%, incrementándose
hasta el 62% en mayores de 65 años14 .
El riesgo que confiere la obesidad
La tabla 1 describe los datos mínimos que deben constar en
¡Adelante con la tecnología! la historia clínica de un sujeto con obesidad. El sistema de
clasificación de Edmonton utiliza 5 categorías, en función
El análisis de la composición corporal debe incorporarse al de la morbilidad y del perfil de riesgo de la enfermedad,
diagnóstico, evaluación clínica y seguimiento de la obesi- siendo capaz de predecir el aumento de la mortalidad20 . Si
dad. La bioimpedancia eléctrica es sencilla y no invasiva, bien no existe ninguna obesidad saludable, definimos a un
estima la masa libre de grasa e indirectamente la grasa cor- obeso metabólicamente sano cuando presenta solo una o
poral total; no hay suficiente validación en IMC > 35 kg/m2 . ninguna de las anormalidades cardiometabólicas asociadas
La densitometría de rayos X de doble fotón es la técnica a la obesidad.
de referencia para evaluar la grasa corporal total y la dis- Cada 5 kg/m2 de incremento en el IMC aumenta signifi-
tribución de la grasa regional15 . Tanto la tomografía axial cativamente la mortalidad para DM2 (HR 2,16), enfermedad
computarizada como la resonancia magnética nuclear son renal crónica (HR 1,59), cardiopatía isquémica (HR 1,39),
técnicas de referencia para estimar el área de grasa visce- accidente cerebrovascular (HR 1,39), enfermedad respira-
ral y subcutánea a nivel de L4-L5, e intrahepática a nivel de toria (HR 1,20) y cáncer (HR 1,10)21 .
D12-L1. Ganancias modestas (≥ 5 kg) tras los 18 años en mujeres
(tras los 20 años en varones) aumentan el riesgo de enfer-
Comorbilidades clásicas ¿qué hay de nuevo? medades del corazón y DM2, independientemente del IMC
inicial.
La alta prevalencia del síndrome metabólico en la obesidad En los obesos de mayor edad la comorbilidad es más pre-
sugiere que sus distintos componentes comparten la lipo- valente y grave, si bien el IMC se asocia con una mortalidad
toxicidad como mecanismo etiopatogénico. La hipertensión relativa más baja22 .
18 A. Lecube et al.

fibra vegetal y ácidos grasos monoinsaturados. Sus benefi-

Tabla 1 ¿Qué datos mínimos, clínicos y de laboratorio,
cios sobre la salud, incluida la mortalidad, están claramente
son necesarios para la correcta evaluación del paciente con
establecidos26 .
obesidad?
En relación con las dietas modificadas en macronutrien-
Peso (kg) y altura (cm) tes, no hay estudios que permitan establecer sus ventajas.
Índice de masa corporal (kg/m2 ) y perímetro de cintura (cm) Ello, junto a su generalización, la ausencia de control
Presión arterial sistólica y diastólica (mm Hg) médico estricto y la presencia de intereses comerciales
Triglicéridos en ayunas (mg/dl o mmol/l) hace que su uso no sea recomendado por la SEEDO. El
Colesterol HDL y LDL (mg/dl o mmol/l) uso de alimentos funcionales tampoco está sustentado por
Glucosa en ayunas (mg/dl o mmol/l) y HbA1c (% o evidencias científicas.
mmol/mol). Cálculo de resistencia a la insulina (HOMA) Los peligros de una dieta inadecuada incluyen desnu-
Niveles de hormona estimulante del tiroides (TSH) y de trición o déficit de micronutrientes, empeorar el riesgo
enzimas hepáticas (ALT y AST) cardiovascular, favorecer trastornos de la conducta alimen-
Proteína C reactiva ultrasensible taria, trasmitir conceptos nutricionales erróneos o fomentar
¿Hay síntomas de apnea del sueño? el sentimiento de frustración.
Enfermedad coronaria La SEEDO se posiciona en contra de cualquier modelo de
¿Alguna medicación que favorece la ganancia de peso? dieta sin aval científico. Es fundamental insistir en la nece-
¿Hace actividad física con regularidad? sidad de una alimentación variada, saludable y equilibrada
¿Otros factores etiológicos? en el contexto de la dieta mediterránea y en la práctica de
¿Otras comorbilidades? HTA, dislipidemia, alteraciones de la ejercicio físico regular.
glucemia (prediabetes/diabetes), osteoartritis,
colelitiasis, RGE, irregularidades menstruales, Actividad física: no todo es lo mismo
infertilidad, depresión y deterioro calidad de vida
¿Alteraciones de la conducta alimentaria (picoteos, La actividad física (AF) representa el movimiento muscular
compulsiones, trastorno por atracón, bulimia nerviosa)? cotidiano. El ejercicio físico (EF) es la AF realizada de forma
estructurada, planeada y repetitiva. La actividad deportiva
ALT: alanina aminotransferasa; AST: aspartato aminotransferasa;
HDL: high density lipoprotein; HOMA: homeostasis model assess- es el EF según unas normas, generalmente con fines competi-
ment; HTA: hipertensión arterial; LDL: low density lipoprotein; tivos. La forma física es el conjunto de beneficios obtenidos
RGE: reflujo gastroesofágico. tras realizar EF.
La AF se mide mediante la unidad metabólica en reposo
(MET), que corresponde a 3,5 ml O2 /kg/min, consumo
Niño obeso, ¿adulto obeso? mínimo de oxígeno para mantener las constantes vitales.
Leer, conducir, trabajar sentado y las labores del hogar gas-
En la infancia el diagnóstico se establece según percentiles tan entre 1 y 3 MET. La AF moderada (andar rápido, ciclismo
de IMC. Entre los 6 y 9 años tiene una prevalencia en España tranquilo) se realiza entre 3 y 6 MET y la AF intensa (correr,
del 18,3% (en Europa ocupa el segundo lugar en varones y saltar, aerobic) a partir de los 6 MET.
el tercero en chicas)23 . La prevalencia de comorbilidades es La pérdida ponderal realizando solo EF es clínicamente
menor que en el adulto, y sí, se proyecta a mayor edad, con irrelevante, si bien existe gran variabilidad individual. Sin
momentos críticos en su desarrollo: el primer año de vida, embargo, un programa de EF es importante, casi impres-
el periodo entre los 4-6 años y la adolescencia24 . El trata- cindible, para dificultar la recuperación del peso perdido27 .
miento se sustenta sobre 3 pilares: reorganizar los hábitos La mejora psicológica que aporta el ejercicio contribuye a
alimentarios, potenciar la actividad física y motivar al niño, reducir la ingesta energética de causa emocional, siendo
con ayuda del entorno familiar y social. más útil en personas con hiperfagia de estrés.

Plan de alimentación ¿Cómo prescribir un programa de ejercicio

físico?
Prevención y tratamiento de la obesidad deben integrar la
consecución y mantenimiento de un estilo de vida saludable Se recomienda un mínimo de 30# diarios de ejercicio de
(alimentación, ejercicio, determinantes sociales, geopolí- intensidad moderada o alta, 5 o más días a la semana
ticos y ambientales). Incluye modificaciones cuantitativas (150# /semana; 300# /semana para prevenir la ganancia pon-
(reducir raciones y aporte energético) y cualitativas (variar deral) y limitar la inactividad física28 .
la proporción de diferentes nutrientes). Combinar EF aeróbico (caminar, trotar, bailar, esquiar,
Un patrón saludable incluye un mayor consumo de verdu- pedalear, etc.) y anaeróbico obtiene mejores resultados que
ras y frutas, seguido, aunque con menor grado de evidencia, realizados de forma aislada29 . Por su efecto sobre la masa
de cereales integrales, lácteos bajos en grasa, pescado, muscular el ejercicio anaeróbico está especialmente indi-
legumbres y frutos secos. Disminuir la ingesta de carnes, cado en personas mayores.
incluyendo carnes procesadas y alimentos azucarados, tam- La prescripción debe ser personalizada, considerando
bién es característico de este patrón25 . preferencias y habilidades de cada persona, condición física,
La dieta mediterránea «hipocalórica» es el modelo que situación cardiorrespiratoria y ortopédica, medicación y dis-
respalda la SEEDO, por representar mejor este enfoque capacidades (tabla 2). Al considerar los efectos adversos,
equilibrado y saludable, con baja ingesta de ácidos grasos considerar la sobrecarga en articulaciones de carga y el
saturados, trans y azúcares añadidos, y un alto consumo de compromiso respiratorio.
Prevención, diagnóstico y tratamiento de la obesidad. Posicionamiento SEEDO 2016 19

Tabla 2 Consejos para iniciar la prescripción de un pro- Tabla 3 Grupos de riesgo que deben identificarse y en los
grama de ejercicio físico en la práctica clínica habitual que realizar una prevención selectiva destinada a evitar la
ganancia ponderal
Consejo 1 Medir el nivel de actividad/inactividad.
Para ello podemos utilizar un Sujetos con sobrepeso
podómetro, según el cual clasificaremos Distribución central de la grasa corporal
al sujeto obeso en sedentario (< 5.000 Personas obesas que han perdido peso
pasos/día), activo moderado Cambios cíclicos de peso
(5.000-10.000 pasos/día), o activo Enfermedades que predispongan a obesidad (genéticas,
saludable (> 10.000 pasos al día). Otra traumatológicas, endocrinas, etc.)
alternativa es la versión corta del Pacientes sometidos a determinados tratamientos
Cuestionario Internacional de Actividad (corticoides, antihistamínicos, ansiolíticos)
Física (IPAQ), validado en castellano, Predisposición familiar a la obesidad y al sedentarismo
que clasifica el nivel de actividad física Factores de riesgo ambiental (bajo nivel sociocultural, falta
en bajo (no realiza), moderado o intenso de disponibilidad de frutas y verduras)
Consejo 2 Establecer como objetivo cambiar e Hábitos nutricionales incorrectos (aumento de ingesta
incrementar el nivel de actividad, según calórica y grasa, de alimentos muy calóricos y bebidas
la situación de cada persona azucaradas, etc.)
Consejo 3 Realizar un mínimo de 30# diarios de Períodos de la vida críticos para la obesidad (gestación, de
ejercicio de moderada a alta intensidad los 5 a 7 años, la adolescencia y la menopausia)
5 o más días a la semana (150# /semana), Antiguos fumadores
pudiendo concentrar todo el ejercicio Sujetos altamente motivados para evitar el aumento de peso
semanal en solo 2 sesiones. Elegir
cualquier actividad que sea agradable,
aceptada por el paciente y fácil de
realizar. Pueden ser actividades
Presente y futuro del tratamiento
cotidianas (como andar o ir en farmacológico
bicicleta), ejercicios programados
Utilizaremos fármacos en el sujeto con IMC > 30 kg/m2 o
supervisados (por ejemplo, clases en
> 27 kg/m2 asociado a comorbilidades mayores, cuando tras
gimnasios), u otras actividades como
3-6 meses en un programa estructurado no pierda > 5% del
nadar, subir escaleras andando, etc.
peso inicial. Si este es bien tolerado y la pérdida ponderal
Consejo 4 Aconsejable realizar calentamiento
supera el 5% del peso inicial el tratamiento debe continuarse
previo, que incluya el movimiento
de forma crónica mientras persista la indicación.
articular, durante unos 10 min, para
Tras orlistat la European Medicines Agency aprobó en
evitar lesiones musculares
2015 2 nuevos fármacos: liraglutida 3,0 mg (Saxenda® )
Consejo 5 Indicar frecuencia e intensidad siendo lo
y la combinación de bupropión (360 mg) con naltrexona
más flexible posible, utilizando ambas
(16 o 32 mg) (Mysimba® ). El primero es agonista del recep-
variables para conseguir el mismo fin. El
tor de GLP1, de administración diaria y subcutánea. Tras
aumento de intensidad de la actividad
56 semanas consigue pérdidas del peso inicial de 8,0 ± 6,7%
aporta mejoras en la forma física. Una
(8,4 ± 7,3 kg)30 . Bupropión/naltrexona se administra por vía
modalidad de entrenamiento de alta
oral, consiguiendo pérdidas de peso del 5,4-8,1%, pudiendo
intensidad y corta duración es el High
ser útil en pacientes con sintomatología depresiva31 . Como
Intensive Interval Training, que consigue
efectos secundarios las náuseas-vómitos son los más desta-
mejoras a nivel cardiorespiratorio
cados con liraglutida; las cefaleas, la sequedad de boca,
Consejo 6 Contactar con algún amigo o hacerlo en
las náuseas y los mareos con bupropión-naltrexona. Ambas
grupo. Utilizar música para marcar el
están contraindicadas en el embarazo. Los efectos secun-
ritmo
darios son transitorios y no suponen una causa principal de
Consejo 7 Mantener un nivel de hidratación
abandono.
adecuado, ingiriendo en total alrededor
Liraglutida contribuye a reducir la presión arterial, mejo-
de 1,5 l de agua antes, durante y
rar los parámetros de riesgo cardiovascular y disminuye la
después del ejercicio. Evitar ingestas de
mortalidad cardiovascular, siendo de elección en pacientes
agua superiores a 200 ml/15 min (tasa
con DM2 o prediabetes32 . Bupropión/naltrexona mejora la
máxima de absorción por parte del
presión arterial y el perfil lipídico.
intestino), lo que genera molestias
intestinales (típico dolor del costado)
Consejo 8 Llevar ropa y calzado adecuado hace el Prevención de la obesidad
ejercicio más agradable y evita lesiones
Consejo 9 Tras el ejercicio dejar unos 5 min de El objetivo es disminuir el desarrollo de sobrepeso y
enfriamiento (por ejemplo caminar obesidad en individuos con peso normal y sobrepeso,
lento), lo que facilita la desaparición del respectivamente, impidiendo la reganancia ponderal. Reco-
lactato muscular mendamos identificar y actuar sobre los grupos de mayor
riesgo (tabla 3)33 .
20 A. Lecube et al.

Debe conseguirse la implicación de la industria ali- cirugía puede modificar la absorción y la biodisponibilidad
mentaria (calidad nutricional y etiquetado), medios de de algunos fármacos43 .
comunicación (información veraz y contrastada), poder Si bien modificar el tracto gastrointestinal puede supo-
legislativo y autoridades (medidas reguladoras y coerciti- ner una alternativa terapéutica para los componentes del
vas sobre la industria, incentivos económicos al consumo síndrome metabólico, no puede recomendarse la cirugía
de ciertos alimentos), administraciones locales (urbanismo), metabólica de forma generalizada44 .
centros educativos (comedores escolares, limitar máquinas Tras la cirugía deben utilizarse métodos anticonceptivos
expendedoras de bebidas azucaradas) y de trabajo (prescin- eficaces, independientes de la absorción intestinal, y evitar
dir de ascensores y medios mecánicos, disponer de áreas de la gestación hasta transcurridos 12-18 meses45 .
esparcimiento) y sociedades científicas. Estas deben liderar
la lucha contra la obesidad, alertar sobre sus consecuencias ¿Dónde tratar al paciente obeso?
y estimular las estrategias de prevención.
Debe elaborarse un único protocolo de valoración y trata-
Tratamiento de la «diabesidad», ¿hay algo miento de la obesidad, que refleje los criterios de derivación
nuevo? entre atención primaria y especializada, facilitando la
comunicación entre profesionales. Actividades de formación
La reducción ponderal es el primer escalón, y debe estar continuada y el desarrollo coordinado de líneas de investi-
presente en todas las fases del tratamiento junto con el gación deben ser una constante46 .
ejercicio34 . El momento del diagnóstico es crítico para pres-
cribir la pérdida ponderal. Financiación
El tratamiento farmacológico de la diabetes está condi-
cionado por la ganancia ponderal asociada con sulfonilureas, La Sociedad Española para el Estudio de la Obesidad (SEEDO)
tiazolidinendionas e insulina. Sin embargo, los agonistas del ha contado con la colaboración no condicionada de Novo
receptor de GLP1 asocian reducciones ponderales de 2,9 kg Nordisk y AstraZeneca.
comparado con placebo, antidiabéticos orales o insulina35 .
De forma similar, la pérdida ponderal con los inhibidores del
SGLT2 se sitúa entre 1,8-2,3 kg versus placebo36 . Conflicto de intereses
La remisión de la DM2 tras la cirugía gastrointestinal
alcanza el 72% a los 2 años, con una tasa de remisión del A. Lecube declara haber recibido honorarios como miembro
30,4% a los 15 años37 . Se ha descrito también una reducción de asesoría científica (Novo Nordisk, AstraZeneca, Janssen)
en la incidencia de complicaciones micro y macrovascula- y por conferencias patrocinadas (Novo Nordisk, AstraZe-
res, y consigue mejor control metabólico que el tratamiento neca, Sanofi, Boehringher-Lilly). D. Bellido declara haber
convencional38,39 . Entre los factores pronósticos asociados a recibido honorarios como miembro de asesoría científica
remisión encontramos menor edad, menor tiempo de evolu- (Novo Nordisk, Boeringher-Lilly, Sanofi) y por conferencias
ción, menor cifra de HbA1c, mayor concentración de péptido patrocinadas (Novo Nordisk, Boeringher-Lilly, Sanofi, Astra-
C, y no precisar tratamiento con insulina40 . En nuestro país, Zeneca, Janssen, Almirall, Novartis, MSD). P.P. García-Luna
la indicación en sujetos con IMC < 35 kg/m2 se limita a la declara haber recibido honorarios como miembro de ase-
participación en ensayos clínicos. soría científica (Novo Nordisk, Vegenat) y por conferencias
patrocinadas (Novo Nordisk, Sanofi, Nestlé, MSD, Janssen).
F.F. Casanueva declara haber recibido becas de investiga-
Cirugía bariátrica
ción, pago por consultorías o conferencias de Novo Nordisk,
Lilly, Pfizer, AstraZeneca, Boheringer Manheim, Novartis y
Indicada cuando el IMC ≥ 40 kg/m2 o en formas menos graves Janssen.
de obesidad (IMC 35-40 kg/m2 ) con comorbilidades graves S. Monereo, M.A. Rubio, P. Martínez-de-Icaya, A. Martí,
asociadas, en sujetos entre 18 y 60 años (individualizando J. Salvador, L. Masmiquel, A. Goday, E. Lurbe, J.M. García-
adolescentes y edad avanzada). Para indicar cualquier téc- Almeida, F.J. Tinahones, E. Palacio, M. Gargallo, I. Bretón,
nica tendremos en cuenta el patrón alimentario, el IMC, las S. Morales-Conde, A. Caixàs, E. Menéndez y M. Puig-Domingo
comorbilidades asociadas y el riesgo quirúrgico. no presentan ningún conflicto de intereses relacionado con
Las expectativas del paciente deben ser moduladas en su participación en este documento.
el preoperatorio. El objetivo de la cirugía es conseguir una
pérdida ponderal que mejore comorbilidades y calidad de
vida. Si bien el by-pass gástrico en Y-de-Roux (BPGYR) se Bibliografía
considera la técnica de referencia, la gastrectomía vertical
está en auge por su simplicidad y efectividad41 . Varios estu- 1. Rubio MA, Salas J, Barbany M, Moreno B, Aranceta J, Bellido D,
dios han mostrado una pérdida ponderal inicial similar al et al. Consenso SEEDO 2007 para la evaluación del sobrepeso
BPGYR, aunque falta evaluar sus resultados a largo plazo42 . y la obesidad y el establecimiento de criterios de intervención
terapéutica. Rev Esp Obes. 2007;5:135---71.
El abordaje laparoscópico debe ser la norma, y la mortalidad
2. Goisser S, Kemmler W, Porzel S, Volkert D, Sieber CC, Bollheimer
intraoperatoria ser < 0,5%. Las principales complicaciones se LC, et al. Sarcopenic obesity and complex interventions with
derivan de infecciones, hemorragias y fallos de sutura41 . nutrition and exercise in community-dwelling older persons-a
Es preciso un seguimiento multidisciplinar a largo plazo, narrative review. Clin Interv Aging. 2015;10:1267---82.
que asegure una pérdida ponderal adecuada y la adheren- 3. Pigeyre M, Yazdi FT, Kaur Y, Meyre D. Recent progress in
cia a estilos de vida saludables; no hay que olvidar que la genetics, epigenetics and metagenomics unveils the pat-
Prevención, diagnóstico y tratamiento de la obesidad. Posicionamiento SEEDO 2016 21

hophysiology of human obesity. Clin Sci (Lond). 2016;130: 22. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin
943---86. MA, et al. Childhood adiposity, adult adiposity, and cardiovas-
4. Singh M. Mood, food and obesity. Front Psychol. 2014;5:925. cular risk factors. N Engl J Med. 2011;365:1876---85.
5. Bereket A, Kiess W, Lustig RH, Muller HL, Goldstone AP, 23. Pérez-Farinós N, López-Sobaler AM, Dal Re MÁ, Villar C, Labrado
Weiss R, et al. Hypothalamic obesity in children. Obes Rev. E, Robledo T, et al. The ALADINO study: A national study of
2015;13:780---98. prevalence of overweight and obesity in Spanish children in
6. Garaulet M, Gomez-Abellan P. Chronobiology and obesity. Nutr 2011. Biomed Res Int. 2013;2013:163687.
Hosp. 2013;28 Suppl 5:114---20. 24. Skinner AC, Perrin EM, Moss LA, Skelton JA. Cardiometabolic
7. Ozanne SE. Epigenetic signatures of obesity. N Engl J Med. risks and severity of obesity in children and young adults. N
2015;372:973---4. Engl J Med. 2015;373:1307---17.
8. Moran CP, Shanahan F. Gut microbiota and obesity: Role in 25. Gargallo M, Breton I, Basulto J, Quiles J, Formiguera X, Salas-
aetiology and potential therapeutic target. Best Pract Res Clin Salvadó J. FESNAD-SEEDO Consensus Group. Evidence-based
Gastroenterol. 2014;28:585---97. nutritional recommendations for the prevention and treatment
9. Mackenbach JD, Rutter H, Compernolle S, Glonti K, Oppert J-M, of overweight and obesity in adults (FESNAD SEEDO consensus
Charreire H, et al. Obesogenic environments: A systematic document). The role of diet in obesity treatment (III/III). Nutr
review of the association between the physical environment Hosp. 2012;27:833---64.
and adult weight status, the SPOTLIGHT project. BMC Public 26. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós
Health. 2014;14:233. F, et al. PREDIMED Study Investigators. Primary prevention of
10. Carmienke S, Freitag MH, Pischon T, Schlattmann P, Fank- cardiovascular disease with a Mediterranean diet. N Engl J Med.
haenel T, Goebel H, et al. General and abdominal obesity 2013;368:1279---90.
parameters and their combination in relation to mortality: A 27. Johns DJ, Hartmann-Boyce J, Jebb SA, Aveyard P. Behavioural
systematic review and meta-regression analysis. Eur J Clin Nutr. weight management review group. Diet or exercise interven-
2013;67:573---85. tions vs combined behavioral weight management programs: A
11. Garvey WT, Garber AJ, Mechanick JI, Bray GA, Dagogo-Jack systematic review and meta-analysis of direct comparisons. J
S, Einhorn D, et al. American Association of Clinical Endo- Acad Nutr Diet. 2014;114:1557---68.
crinologists and American College of Endocrinology position 28. Stegenga H, Haines A, Jones K, Wilding J. Guideline develop-
statement on the 2014 advanced framework for a new dia- ment group. Identification, assessment, and management of
gnosis of obesity as a chronic disease. Endocr Pract. 2014;20: overweight and obesity: Summary of updated NICE guidance.
977---89. BMJ. 2014;349:g6608.
12. Gómez-Ambrosi J, Silva C, Catalán V, Rodríguez A, Galofré JC, 29. Sigal RJ, Alberga AS, Goldfield GS, Prud’homme D, Hadjiyanna-
Escalada J, et al. Clinical usefulness of a new equation for esti- kis S, Gougeon R, et al. Effects of aerobic training, resistance
mating body fat. Diabetes Care. 2012;35:383---8. training, or both on percentage body fat and cardiometabolic
13. Aranceta-Bartrina J, Pérez-Rodrigo C, Alberdi-Aresti G, Ramos- risk markers in obese adolescents: The healthy eating aerobic
Carrera N, Lázaro-Masedo S. Prevalence of general obesity and and resistance training in youth randomized clinical trial. JAMA.
abdominal obesity in the Spanish adult population (aged 25-64 2014;168:1006---14.
years) 2014-2015: The ENPE Study. Rev Esp Cardiol (Engl Ed). 30. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A,
2016;69:579---87. Krempf M, et al. A randomized, controlled trial of 3.0 mg of
14. Gutierrez-Fisac JL, Guallar-Castillón P, León-Muñoz LM, Gra- liraglutide in weight management. N Engl J Med. 2015;373:
ciani A, Banegas JR, Rodriguez-Artalejo F. Prevalence of general 11---22.
and abdominal obesity in the adult population of Spain, 2008- 31. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadau-
2010: The ENRICA study. Obes Rev. 2012:388---92. ria M, Erickson J, et al. Effect of naltrexone plus bupropion on
15. Kaul S, Rothney MP, Peters DM, Wacker WK, Davis CE, Shapiro weight loss in overweight and obese adults (COR-1): A multi-
MD, et al. Dual-energy X-ray absorptiometry for quantification center, randomized, double-blind, placebo-controlled, phase 3
of visceral fat. Obesity. 2012;20:1313---8. trial. Lancet. 2010;376:595---605.
16. Goday A, Barneto I, García-Almeida JM, Blasco A, Lecube A, 32. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF,
Grávalos C, et al. Obesity as a risk factor in cancer: A natio- Nauck MA, et al. Liraglutide and cardiovascular outcomes in
nal consensus of the Spanish Society for the Study of Obesity type 2 diabetes. N Engl J Med. 2016;375:311---22.
and the Spanish Society of Medical Oncology. Clin Transl Oncol. 33. Brauer P, Connor Gorber S, Shaw E, Singh H, Bell N, Shane
2015;17:763---71. AR, et al. Recommendations for prevention of weight gain
17. Vargas V, Allende H, Lecube A, Salcedo MT, Baena-Fustegueras and use of behavioural and pharmacologic interventions to
JA, Fort JM, et al. Surgically induced weight loss by gastric manage overweight and obesity in adults in primary care. CMAJ.
bypass improves non-alcoholic fatty liver disease in morbid 2015;187:184---95.
obese patients. World J Hepatol. 2012;4:382---8. 34. Wadden TA, Neiberg RH, Wing RR, Clark JM, Delahanty LM, Hill
18. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato JO, et al. Four-year weight losses in the Look AHEAD study: Fac-
KA, et al. 2013 AHA/ACC/TOS Guideline for the management of tors associated with long-term success. Obesity (Silver Spring).
overweight and obesity in adults. Circulation. 2014;129 25 Suppl 2011;19:1987---8.
2:S102---38. 35. Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects
19. Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, of glucagon-like peptide-1 receptor agonista on weight loss:
Wedel H, et al. Bariatric surgery and long-term cardiovascular Systematic review and meta-analyses of randomised controlled
events. JAMA. 2012;307:56---65. trials. BMJ. 2012;344:d7771.
20. Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the 36. Clar C, Gill JA, Court R, Waugh N. Systematic review of SGLT2
Edmonton obesity staging system to predict mortality in a receptor inhibitors in dual or triple therapy in type 2 diabetes.
population-representative cohort of people with overweight BMJ Open. 2012;18:e001007.
and obesity. CMAJ. 2011;183:E1059---66. 37. Sjöström L, Peltonen M, Jacobson P, Ahlin S, Andersson-
21. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all- Assarsson J, Anveden Å, et al. Association of bariatric
cause mortality with overweight and obesity using standard surgery with long-term remission of type 2 diabetes and
body mass index categories: A systematic review and meta- with microvascular and macrovascular complications. JAMA.
analysis. JAMA. 2013;309:71---82. 2014;311:2297---304.
22 A. Lecube et al.

38. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, 43. Stein J, Stier C, Raab H, Weiner R. Review article: The nutri-
Navaneethan SD, et al. Bariatric surgery versus intensive medi- tional and pharmacological consequences of obesity surgery.
cal therapy for diabetes-3-year outcomes. N Engl J Med. Aliment Pharmacol Ther. 2014;40:582---609.
2014;370:2002---13. 44. Cordera R, Adami GF. From bariatric to metabolic surgery: Loo-
39. Mingrone G, Panunzi S, de Gaetano A, Guidone C, king for a ‘‘disease modifier’’ surgery for type 2 diabetes. World
Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventio- J Diabetes. 2016;7:27---33.
nal medical therapy for type 2 diabetes. N Engl J Med. 2012;366: 45. González I, Rubio MA, Cordido F, Bretón I, Morales MJ, Vilarrasa
1577---85. N, et al. Maternal and perinatal outcomes after bariatric
40. Still CD, Wood GC, Benotti P, Petrick AT, Gabrielsen J, Strodel surgery: A Spanish multicenter study. Obes Surg. 2015;25:
WE, et al. Preoperative prediction of type 2 diabetes remission 436---42.
alter Roux-en-Y-gastric bypass surgery: A retrospective cohort 46. Mories MT, Astorga R, Soler J, Abellán MT, Aguilar M, Blay
study. Lancet Diabetes Endocrinol. 2014;2:38---45. V, et al. Criterios de derivación desde atención primaria a
41. Lecube A, de Hollanda A, Calañas A, Vilarrasa N, Rubio MA, Bre- atención especializada de pacientes con obesidad. Criterios
ton I, et al. Trends in bariatric surgery in spain in the twenty-first de buena práctica en atención especializada. Endocrinol Nutr.
century: Baseline results and 1-month follow up of the RICIBA, 2005;52:38---9.
a national registry. Obes Surg. 2016;26:1836---42.
42. Puzziferri N, Roshek TB 3rd, Mayo HG, Gallagher R, Belle SH,
Livingston EH. Long-term follow-up after bariatric surgery: A
systematic review. JAMA. 2014;312:934---42.
Sistema de Estadificación de la
Obesidad de Edmonton (EOSS) *
ESTADIO 0

Sin factores de riesgo aparentes

relacionados con la obesidad (p. ej., TA,
lípidos séricos, glucosa en ayunas, etc., Sin factores reportados EOSS
dentro del rango normal), sin síntomas
físicos, sin psicopatología, sin limitaciones
funcionales y (o) deterioro del bienestar

* modificado
ESTADIO 1

Presencia de factores de riesgo

subclínicos relacionados con la obesidad
(por ej., hipertensión limítrofe, glucosa TA ≥120/80
en ayunas alterada, enzimas hepáticas Glucosa en ayunas ≥100 y <126 mg/dL
elevadas, etc.) Colesterol ≥200 y <240 mg/dL
Síntomas físicos leves (p. ej., disnea con Triglicéridos ≥150 y <200 mg/dL
esfuerzos moderados, dolores y HDL <60 mg/dL
molestias ocasionales, fatiga, etc.) Falta de aire durante la actividad física.
Limitaciones funcionales leves
Psicopatología leve y (o)
Deterioro leve del bienestar.
ESTADIO 2

Presencia de enfermedad crónica Hipertensión diagnosticada o

relacionada con la obesidad establecida medicamentos para la hipertensión
(p. ej., TA ≥140/90 mm Hg
hipertensión, diabetes tipo 2, apnea del DBT2
sueño, osteoartritis, enfermedad por Glucosa en ayunas ≥126 mg/dL
reflujo, síndrome de ovario poliquístico, Hipercolesterolemia diagnosticada
trastorno de ansiedad, etc.) Colesterol ≥240 mg/dL
Limitaciones moderadas en las actividades Hipertrigliceridemia diagnosticada
de la vida diaria y (o) Triglicéridos ≥200 mg/dL
Deterioro moderado del bienestar HDL <40 mg/dL
Gota
Depresión
Fatiga
Incontinencia urinaria
Lumbalgia
Rigidez articular
Situación emocional informada de
“generalmente triste”, o
Salud autoinformada de “justa”
ESTADIO 3

Dolor de pecho reportado

Dolor de pecho durante el ejercicio
Daño de órgano terminal establecido (p. Infarto de miocardio
ej. Infarto de miocardio, insuficiencia Dolor en la pantorrilla durante el ejercicio
cardíaca, complicaciones diabéticas, Stroke
osteoartritis incapacitante, etc.) Falta de aire al dormir
Psicopatología significativa Falta de aire al sentarse
Limitaciones funcionales significativas y Consulta psiquiátrica o psicológica, o
(o) Cardiomegalia moderada o severa
Deterioro significativo del bienestar Situación emocional informada de “a
menudo deprimido”, o
Salud autoinformada de “pobre”
ESTADIO 4

Discapacidades severas (potencialmente Insuficiencia cardíaca severa

en etapa terminal) de enfermedades Enfermedad renal terminal
crónicas relacionadas con la obesidad Artrosis severa
Psicopatología incapacitante severa
Limitaciones funcionales severas y (o)
Deterioro severo del bienestar

Bibliografía:
1.Kuk JL, Ardern CI, Church TS, et al. Edmonton Obesity Staging System: association
with weight history and mortality risk. Appl Physiol Nutr Metab.
2011;36(4):570‐576. [Medline]
2.Schwarz AC, Billeter AT, Scheurlen KM, Blüher M, Müller-Stich BP. Comorbidities as
an Indication for Metabolic Surgery. Visc Med. 2018;34(5):381‐387. [Medline]
 Universidad Peruana de Ciencias Aplicadas
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Current Medical Diagnosis & Treatment 2024

31­04: Obesity

Katherine H. Saunders; Leon I. Igel

Key Clinical Updates in Obesity

In a meta­analysis of eight RCTs, semaglutide is associated with a 10.76% greater mean total body weight loss than placebo. In light of its greater efficacy in
reducing total body weight, a 2022 American Gastroenterological Association guideline endorses the use of semaglutide over other anti­obesity medications.

In a propensity score­matched study of 3018 patient­pairs conducted at a surgical weight loss center, total body weight loss at 3 years was 19% following
surgical sleeve gastrectomy versus 14% following endoscopic sleeve gastroplasty.

Grunvald E et al. Gastroenterology. [PMID: 36273831]

Alqahtani AR et al. Gastrointest Endosc. [PMID: 35248571]

ESSENTIALS OF DIAGNOSIS

Disorder of energy homeostasis; BMI ≥ 30.

Central obesity (abdomen and flank) is a greater health risk than excess weight in the lower body (buttocks and thighs).

Associated with numerous comorbid conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, heart disease, stroke, and obstructive
sleep apnea.

DEFINITION & MEASUREMENT

Obesity is a multifactorial, chronic disease characterized by an accumulation of visceral and subcutaneous fat, which promotes adipocyte dysfunction. Obesity
predisposes to a wide variety of comorbid conditions. BMI typically correlates with excess adipose tissue but does not reflect body composition. It is calculated by
dividing body weight in kilograms by height in meters squared (kg/m2) (eTable 31–8). The National Institutes of Health defines normal BMI as 18.5–24.9.
Overweight is defined as BMI 25–29.9. Class I obesity is 30–34.9, class II is 35–39.9, and class III is 40 and above. Central obesity (excess adipose tissue around the
waist and flank) is a greater health risk than lower body obesity (adipose tissue in the thighs and buttocks). Patients with obesity and increased abdominal
circumference (greater than 102 cm or 40 inches in men and 88 cm or 35 inches in women) or high waist–hip ratios (greater than 1.0 in men and 0.85 in women)
have a greater risk of weight­related comorbid conditions and early death than patients with the same BMI and lower ratios. There are different abdominal
circumference cutoffs for different populations. Visceral fat within the abdominal cavity is more hazardous to health than subcutaneous fat around the abdomen.
Over 40% of Americans have obesity.

HEALTH CONSEQUENCES OF OBESITY

Obesity is associated with significant increases in both morbidity and mortality, and many disorders occur with greater frequency in patients with obesity (eFigure
31–1). Obesity­related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and many cancers. Over 200
health conditions ranging from hypertension and CAD to thromboembolic and skin disorders are more prevalent in patients with obesity. Patients with higher BMI
have increased surgical and obstetric risks and higher rates of major depression and binge­eating disorder. Most patients with excess weight have experienced
weight bias, stigma, and discrimination.

eFigure 31–1.

Downloaded
Role of obesity2025­1­21 9:1 P YourofIPweight­related
in the pathophysiology is diseases. Short arrows refer to a change in the indicated parameter, and long arrows indicate a
consequence of that change. In some cases,Leon
31­04: Obesity, Katherine H. Saunders; I. Igel
evidence Page
is epidemiologic; in others, it is experimental. (Modified from Bray GA. Pathophysiology of obesity. Am1J/ Clin
11
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
Nutr. 1992;55:488S.)
health conditions ranging from hypertension and CAD to thromboembolic and skin disorders are more prevalent in patients with obesity. Patients with higher BMI
have increased surgical and obstetric risks and higher rates of major depression and binge­eating disorder. Most Universidad Peruana
patients with excess de Ciencias
weight Aplicadas
have experienced
weight bias, stigma, and discrimination. Access Provided by:

eFigure 31–1.

Role of obesity in the pathophysiology of weight­related diseases. Short arrows refer to a change in the indicated parameter, and long arrows indicate a
consequence of that change. In some cases, evidence is epidemiologic; in others, it is experimental. (Modified from Bray GA. Pathophysiology of obesity. Am J Clin
Nutr. 1992;55:488S.)

ETIOLOGY
Both genetic and environmental factors contribute to the development of obesity. Twin studies demonstrate that genetics account for 40–90% of variation in BMI,
although only a small percentage is due to single gene mutations. Most obesity develops from interactions of multiple genes, environmental factors, and
behavior. The rapid increase in obesity in the last several decades points to major roles for environmental and behavioral factors.

MEDICAL EVALUATION OF THE PATIENT WITH OBESITY

Medical history should determine the age at onset of weight gain, recent weight changes, family history of obesity, occupational history, eating and exercise
behavior, previous weight loss experience, and psychosocial factors, including assessment for mood and eating disorders.

Physical examination should assess BMI, degree and distribution of body fat, and overall nutritional status. Signs of secondary causes of obesity should be
pursued; however, less than 1% of patients have an identifiable cause. Cushing syndrome is an example that can be diagnosed by physical examination and
laboratory testing in patients with unexplained weight gain (see Chapter 28). All patients should be screened for weight­related comorbid conditions, including
obstructive sleep apnea. Blood pressure, waist circumference, fasting glucose, comprehensive metabolic profile, lipid panel, and hemoglobin A1c should be
measured as well as other laboratory tests as clinically indicated.

TREATMENT
Weight loss of 5–10% body weight is sufficient in many patients with obesity to achieve clinically relevant improvements in many risk factors, and the risk
reduction appears to be “dose­related.” Magnitude of weight loss at 1 year is strongly associated with improvements in many parameters including blood sugar,
blood pressure, triglycerides, and HDL cholesterol.

Successful treatment of obesity requires a multidisciplinary approach to counteract the body’s resistance to weight loss. Diet, physical activity, and behavioral
modifications are the cornerstone of weight management. Many dietary strategies can be effective for weight loss. Recommendations should be tailored to a
patient’s preferences, as dietary adherence is associated with greater weight loss. Dietary instructions should emphasize intake of predominantly “unprocessed”
foods, with special attention to limiting foods that provide large amounts of calories without other nutrients, such as ultra­processed foods, sugary drinks, fast
food, junk food, and sweets. A Mediterranean diet can be a good option for patients at high cardiovascular risk, since it has been shown to reduce the incidence of
major cardiovascular events. A low­glycemic­index diet can curb hunger and decrease cravings by reducing blood sugar fluctuations. Meal replacement diets can
facilitate
Downloaded weight loss but may
2025­1­21 9:1bePless sustainable.
Your IP is Registered dietitians can provide dietary education and customize dietary plans.
31­04: Obesity, Katherine H. Saunders; Leon I. Igel Page 2 / 11
Long­term changes
©2025 McGraw in eating
Hill. behavior
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Reserved. to maintain
Terms of Use •weight loss,
Privacy and behavior
Policy • Notice •modification
Accessibility strategies support weight loss maintenance. It is
important to emphasize meal planning and self­monitoring, including weighing at regular intervals. Some patients maintain a food log to track caloric intake. Self­
monitoring aids in behavioral change and provides the practitioner with additional data to guide recommendations. Patients can learn to recognize “eating cues”
modifications are the cornerstone of weight management. Many dietary strategies can be effective for weight loss. Recommendations should be tailored to a
Universidad Peruana de Ciencias Aplicadas
patient’s preferences, as dietary adherence is associated with greater weight loss. Dietary instructions should emphasize intake of predominantly “unprocessed”
Access Provided by:
foods, with special attention to limiting foods that provide large amounts of calories without other nutrients, such as ultra­processed foods, sugary drinks, fast
food, junk food, and sweets. A Mediterranean diet can be a good option for patients at high cardiovascular risk, since it has been shown to reduce the incidence of
major cardiovascular events. A low­glycemic­index diet can curb hunger and decrease cravings by reducing blood sugar fluctuations. Meal replacement diets can
facilitate weight loss but may be less sustainable. Registered dietitians can provide dietary education and customize dietary plans.

Long­term changes in eating behavior are required to maintain weight loss, and behavior modification strategies support weight loss maintenance. It is
important to emphasize meal planning and self­monitoring, including weighing at regular intervals. Some patients maintain a food log to track caloric intake. Self­
monitoring aids in behavioral change and provides the practitioner with additional data to guide recommendations. Patients can learn to recognize “eating cues”
(eg, emotional, situational) and how to avoid or control them. Weight maintenance can be more challenging than initial weight loss, so it is important to continue
regular follow­up to ensure adherence to a treatment plan.

Physical activity offers several advantages for patients trying to achieve and maintain weight loss. Aerobic exercise increases daily energy expenditure and
partially prevents the decrease in basal energy expenditure (BEE) resulting from weight loss. It is useful for long­term weight maintenance and helps preserve lean
body mass. The combination of exercise and diet results in greater weight loss than diet or exercise alone. Higher intensity exercise is associated with more weight
loss. Up to 1 hour of moderate exercise per day is associated with long­term weight maintenance in individuals who have successfully lost weight.

The American College of Sports Medicine recommends 150 minutes of moderate­intensity aerobic physical activity (such as tennis or brisk walking) per week, 75
minutes of vigorous­intensity aerobic exercise (such as jogging or swimming laps) per week, or an equivalent combination of moderate­ and vigorous­intensity
aerobic activity. Exercise should be spread throughout the week. Resistance training is also recommended at least twice per week. Exercise physiologists and
physical therapists can provide support for patients.

Medications can have unpredictable and variable effects on patients’ weight, so it is important to review patients’ medication regimens and balance their benefits
against the probability of weight gain. Multiple medications are associated with weight gain, including corticosteroids, contraceptives (and other hormonal
agents), and certain antidiabetic, antihypertensive, antidepressant, antipsychotic, antiepileptic, and antihistamine agents. Table 31–1 provides an overview of
weight­gaining medications as well as potential alternatives. When possible, clinicians should prescribe weight­neutral– or weight­loss–promoting medications. If
there are no alternatives, weight gain can be prevented or lessened by selecting the lowest clinically effective dose for the shortest duration.

Table 31–1.
Medications and their effects on weight.

Result: Weight Neutral (or Minor Result: Weight

Drug Class Result: Weight Gain
Weight Gain) Loss

Antidiabetics Insulin Alpha­glucosidase inhibitors GLP­1 agonists

Meglitinides Bromocriptine Metformin
Sulfonylureas Colesevelam Pramlintide
Thiazolidinediones DPP­4 inhibitors SGLT2 inhibitors

Antihypertensives Alpha blockers ACE inhibitors

Beta­blockers (atenolol, metoprolol, nadolol, propranolol) ARBs
Beta­blockers (carvedilol, nebivolol)
Calcium channel blockers
Thiazides

Antidepressants Lithium SSRIs (fluoxetine, sertraline) Bupropion

MAO inhibitors
Mirtazapine
SNRIs (duloxetine, venlafaxine)
SSRIs (citalopram, paroxetine)
Tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine,
nortriptyline)

Antipsychotics Clozapine Lurasidone

Haloperidol Ziprasidone
Olanzapine
Quetiapine
Risperidone

Downloaded 2025­1­21Carbamazepine
Antiepileptics 9:1 P Your IP is Lamotrigine Topiramate
31­04: Obesity, Katherine H. Saunders; Leon I. Igel
Gabapentin Levetiracetam ZonisamidePage 3 / 11
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Phenytoin
Valproic acid
Medications can have unpredictable and variable effects on patients’ weight, so it is important to review patients’ medication regimens and balance their benefits
against the probability of weight gain. Multiple medications are associated with weight gain, including corticosteroids, contraceptives
Universidad Peruana (and
deother hormonal
Ciencias Aplicadas
agents), and certain antidiabetic, antihypertensive, antidepressant, antipsychotic, antiepileptic, and antihistamine agents.
Access Table
Provided by: 31–1 provides an overview of
weight­gaining medications as well as potential alternatives. When possible, clinicians should prescribe weight­neutral– or weight­loss–promoting medications. If
there are no alternatives, weight gain can be prevented or lessened by selecting the lowest clinically effective dose for the shortest duration.

Table 31–1.
Medications and their effects on weight.

Result: Weight Neutral (or Minor Result: Weight

Drug Class Result: Weight Gain
Weight Gain) Loss

Antidiabetics Insulin Alpha­glucosidase inhibitors GLP­1 agonists

Meglitinides Bromocriptine Metformin
Sulfonylureas Colesevelam Pramlintide
Thiazolidinediones DPP­4 inhibitors SGLT2 inhibitors

Antihypertensives Alpha blockers ACE inhibitors

Beta­blockers (atenolol, metoprolol, nadolol, propranolol) ARBs
Beta­blockers (carvedilol, nebivolol)
Calcium channel blockers
Thiazides

Antidepressants Lithium SSRIs (fluoxetine, sertraline) Bupropion

MAO inhibitors
Mirtazapine
SNRIs (duloxetine, venlafaxine)
SSRIs (citalopram, paroxetine)
Tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine,
nortriptyline)

Antipsychotics Clozapine Lurasidone

Haloperidol Ziprasidone
Olanzapine
Quetiapine
Risperidone

Antiepileptics Carbamazepine Lamotrigine Topiramate

Gabapentin Levetiracetam Zonisamide
Pregabalin Phenytoin
Valproic acid

Contraceptives Medroxyprogesterone acetate Barrier methods

IUDs
Surgical sterilization

Antihistamines First­generation antihistamines Second­ and third­generation antihistamines

Steroids Glucocorticoids Inhaled steroids

Topical steroids

DPP­4, dipeptidyl peptidase­4; GLP­1, glucagon­like peptide­1; SGLT2, sodium­glucose co­transporter 2.

Reproduced with permission from Igel LI et.al. Practical use of pharmacotherapy for obesity. Gastroenterology. 2017;152(7):1765–1779.

Weight loss achieved by lifestyle modification alone is often limited and difficult to maintain. Reduced calorie intake and increased energy expenditure are
counteracted by adaptive physiologic responses. Appetite increases and resting metabolic rate (RMR) decreases disproportionately to what would be expected
based on changes in body composition. This phenomenon is called metabolic adaptation or adaptive thermogenesis. It inhibits weight loss and leads to weight
regain. As a result, patients may require antiobesity medications, bariatric surgery, devices, or endoscopic bariatric therapies to achieve and maintain significant
weight loss.
Downloaded 2025­1­21 9:1 P Your IP is
31­04: Obesity,
Antiobesity Katherine(Table
medications H. Saunders;
31–2) canLeon I. Igel in patients with a BMI 30 or higher, or a BMI 27 or higher with weight­related comorbidities.
be considered Page 4 / 11
Some
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
agents affect mechanisms regulating appetite through serotonergic, dopaminergic, or noradrenergic pathways. They target the arcuate nucleus of the
hypothalamus to stimulate the anorexigenic pro­opiomelanocortin (POMC) neurons, which promote satiety. Medications approved for weight management
should be viewed as additions to diet and exercise for patients who have been unsuccessful with lifestyle changes alone. The six most widely prescribed
 Reproduced with permission from Igel LI et.al. Practical use of pharmacotherapy for obesity. Gastroenterology. 2017;152(7):1765–1779.

Universidad Peruana de Ciencias Aplicadas

Weight loss achieved by lifestyle modification alone is often limited and difficult to maintain. Reduced calorie intake and increased energy expenditure are
Access Provided by:
counteracted by adaptive physiologic responses. Appetite increases and resting metabolic rate (RMR) decreases disproportionately to what would be expected
based on changes in body composition. This phenomenon is called metabolic adaptation or adaptive thermogenesis. It inhibits weight loss and leads to weight
regain. As a result, patients may require antiobesity medications, bariatric surgery, devices, or endoscopic bariatric therapies to achieve and maintain significant
weight loss.

Antiobesity medications (Table 31–2) can be considered in patients with a BMI 30 or higher, or a BMI 27 or higher with weight­related comorbidities. Some
agents affect mechanisms regulating appetite through serotonergic, dopaminergic, or noradrenergic pathways. They target the arcuate nucleus of the
hypothalamus to stimulate the anorexigenic pro­opiomelanocortin (POMC) neurons, which promote satiety. Medications approved for weight management
should be viewed as additions to diet and exercise for patients who have been unsuccessful with lifestyle changes alone. The six most widely prescribed
antiobesity medications approved by the FDA are phentermine, orlistat, phentermine/topiramate extended­release (ER), naltrexone sustained­release
(SR)/bupropion SR, liraglutide 3.0 mg, and semaglutide 2.4 mg. Table 31–2 provides an overview of these medications. In addition to producing weight loss, each
medication improves biomarkers including blood sugar, blood pressure, and lipids. Three of the agents approved since 2012 have stopping rules, which provide
weight loss thresholds after 12–16 weeks of treatment under which medication discontinuation is suggested.

Table 31–2.
Medications tested in clinical trials for treatment of obesity.

Most
Mechanism, Dosage, Weight
Trial and Common Poor
Medication and Available Trial Arms Loss Good Candidates
Duration Adverse Candidates
Formulations (%)
Events

Phentermine Adrenergic agonist Aronne LJ et 15 mg daily 6.06* Dry mouth, Younger patients who Patients with

(Adipex,1 Lomaira2) 8–37.5 mg daily (8 mg al3 28 weeks insomnia, need assistance with uncontrolled

Schedule IV controlled dose can be prescribed 7.5 mg daily 5.45* dizziness, appetite suppression hypertension,

substance up to three times daily) irritability active or

NOTE: approved for Capsule, tablet Placebo (topiramate 1.71 unstable

short­term use (up to 3 extended­release and coronary

months) phentermine/topiramate disease,

extended­release arms hyperthyroidism,
excluded) glaucoma,
anxiety,
insomnia, or
general
sensitivity to
stimulants
Patients with a
history of drug
abuse or recent
MAO inhibitor
use
Patients who are
pregnant

Orlistat (Alli,4 Xenical5) Lipase inhibitor XENDOS6 120 mg three times daily 9.6 Fecal Patients with Patients with
60–120 mg three times 208 weeks (week urgency, oily hypercholesterolemia malabsorption
daily with meals 52)* stool, flatus and/or constipation syndromes or
Capsule 5.25 with who can limit their other GI

(week discharge, intake of dietary fat conditions that

fecal predispose to GI
208)*
incontinence upset/diarrhea

Placebo 5.61 Patients who

(week cannot modify

52) the fat content

2.71 of their diets

(week Patients who are

208) pregnant
Downloaded 2025­1­21 9:1 P Your IP is
31­04: Obesity, Katherine H. Saunders; Leon I. Igel Page 5 / 11
©2025Phentermine/Topiramate
McGraw Hill. All RightsAdrenergic Use8• Privacy 15/92
Reserved. Terms ofEQUIP Policymg daily 10.9*
• Notice • Accessibility Paresthesias, Younger patients who Patients with
Extended­release agonist/neurostabilizer 56 weeks dizziness, need assistance with uncontrolled
(Qsymia)7 3.75/23–15/92 mg daily 3.75/23 mg daily 5.1* dysgeusia, appetite suppression hypertension,
 Placebo 5.61 Patients who
Universidad Peruana de Ciencias Aplicadas
(week cannot modify
Access Provided by:
52) the fat content

2.71 of their diets

(week Patients who are

208) pregnant

Phentermine/Topiramate Adrenergic EQUIP8 15/92 mg daily 10.9* Paresthesias, Younger patients who Patients with
Extended­release agonist/neurostabilizer 56 weeks dizziness, need assistance with uncontrolled
(Qsymia)7 3.75/23–15/92 mg daily 3.75/23 mg daily 5.1* dysgeusia, appetite suppression hypertension,
Schedule IV controlled (dose titration) insomnia, active or
substance Capsule Placebo 1.6 constipation, unstable
dry mouth coronary
CONQUER9 56 15/92 mg daily 9.8* disease,
weeks hyperthyroidism,
glaucoma,
7.5/46 mg daily 7.8* anxiety,
insomnia, or
Placebo 1.2 general
(weeks sensitivity to
0–56) stimulants
Patients with a
SEQUEL10 15/92 mg daily 10.5* history of drug
108 weeks (52­ abuse or recent
week 7.5/46 mg daily 9.3* MAO inhibitor
extension of use
CONQUER Placebo 1.8 Patients with a
trial) (weeks history of
0–108) nephrolithiasis
Patients who are
pregnant or
trying to
conceive

Naltrexone/Bupropion Opioid receptor COR­I12 16/180 mg twice daily 6.1* Nausea, Patients who describe Patients with
sustained­release antagonist/dopamine 56 weeks vomiting, cravings for food uncontrolled

(Contrave)11 and norepinephrine 8/180 mg twice daily 5.0* constipation, and/or addictive hypertension,
reuptake inhibitor 8/90 headache, behaviors related to uncontrolled
mg daily to 16/180 mg Placebo 1.3 dizziness, food; patients who pain, recent MAO
twice daily Tablet insomnia, are trying to quit inhibitor use,
COR­II13 16/180 mg twice daily 6.4* dry mouth smoking, reduce history of
56 weeks alcohol intake, and/or seizures, or any
Placebo 1.2 who have condition that
concomitant predisposes to
COR­BMOD14 16/180 mg twice daily 9.3* depression seizure, such as
56 weeks anorexia/bulimia
Placebo 5.1 nervosa, abrupt
discontinuation
COR­ 16/180 mg twice daily 5.0* of alcohol,
DIABETES15 benzodiazepines,
56 weeks Placebo 1.8 barbiturates, or
antiepileptic
drugs
Patients who are
pregnant

Liraglutide 3.0 mg GLP­1 receptor agonist SCALE Obesity 3.0 mg daily 8.0* Nausea, Patients who report Patients with a
(Saxenda)16 0.6–3.0 mg daily and vomiting, inadequate meal history of
Prefilled pen for Prediabetes17 Placebo 2.6 diarrhea, satiety, and/or have pancreatitis,
Downloaded 2025­1­21 9:1 P Your IP is
subcutaneous injection constipation, type 2 diabetes, personal/family
31­04: Obesity, Katherine H. Saunders; Leon I. Igel 56 weeks Page 6 / 11
dyspepsia, prediabetes, or history of MTC or
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SCALE 3.0 mg daily 6* abdominal impaired glucose MEN2

Diabetes18 pain tolerance Patients with an

 Patients who are
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pregnant
Access Provided by:

Liraglutide 3.0 mg GLP­1 receptor agonist SCALE Obesity 3.0 mg daily 8.0* Nausea, Patients who report Patients with a
(Saxenda)16 0.6–3.0 mg daily and vomiting, inadequate meal history of
Prefilled pen for Prediabetes17 Placebo 2.6 diarrhea, satiety, and/or have pancreatitis,
subcutaneous injection 56 weeks constipation, type 2 diabetes, personal/family
dyspepsia, prediabetes, or history of MTC or
SCALE 3.0 mg daily 6* abdominal impaired glucose MEN2

Diabetes18 pain tolerance Patients with an

56 weeks Patients requiring use aversion to

of concomitant needles
SCALE 1.8 mg daily 4.7* psychiatric Patients who are

Maintenance19 medications pregnant

56 weeks Placebo 2.0

(after initial ≥
5% weight 3.0 mg daily 6.2*

loss with low­

calorie diet) Placebo 0.2

Semaglutide 2.4 mg GLP­1 receptor agonist STEP 120 Placebo 2.4 Nausea, Patients who report Patients with a
(Wegovy) 0.25–2.4 mg weekly 68 weeks 2.4 mg weekly 14.9* vomiting, inadequate meal history of
Prefilled pen for diarrhea, satiety, and/or have pancreatitis,
subcutaneous injection STEP 221 Placebo 3.4 constipation, type 2 diabetes, personal/family

68 weeks 1.0 mg weekly 7.0* dyspepsia, prediabetes, or history of MTC or

2.4 mg weekly abdominal impaired glucose MEN2
9.4*
pain tolerance Patients with an

Placebo 5.7 Patients requiring use aversion to

STEP 322
2.4 mg weekly of concomitant needles
68 weeks 16.0*
psychiatric Patients who are

Placebo +6.9 medications pregnant

STEP 423
68 weeks 2.4 mg weekly 7.9*
(after 20­week
run in with
semaglutide
titrated to 2.4
mg weekly)

*P < 0.001 versus placebo.

1Adipex [package insert]. Tulsa, OK: Physicians Total Care, Inc; 2012.

2Lomaira [package insert]. Newtown, PA: KVK­TECH, INC; 2016.

3Aronne LJ et al. Evaluation of phentermine and topiramate versus phentermine/topiramate extended­release in obese adults. Obesity (Silver Spring). 2013;21:2163.

4Alli [package insert]. Moon Township, PA: GlaxoSmithKline Consumer Healthcare, LP; 2015.

5Xenical [package insert]. South San Francisco, CA: Genentech USA, Inc; 2015.

6Torgerson JS et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention

of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155.

7Qsymia [package insert]. Mountain View, CA: VIVUS, Inc; 2012.

8Allison DB et al. Controlled­release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20:330.

9Gadde KM et al. Effects of low­dose, controlled­release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults

(CONQUER): a randomised, placebo­controlled, phase 3 trial. Lancet. 2011;377:1341.

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10Garvey WT et al. Two­year sustained weight loss and metabolic benefits with controlled­release phentermine/topiramate in obese and overweight adults (SEQUEL): a
31­04: Obesity, Katherine H. Saunders; Leon I. Igel Page 7 / 11
randomized,
©2025 McGrawplacebo­controlled,
Hill. All Rightsphase 3 extensionTerms
Reserved. study. Am J Clin •Nutr.
of Use 2012;95:297.
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11Contrave [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2014.
 7Qsymia [package insert]. Mountain View, CA: VIVUS, Inc; 2012.
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Access Provided by:
8Allison DB et al. Controlled­release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20:330.

9Gadde KM et al. Effects of low­dose, controlled­release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults

(CONQUER): a randomised, placebo­controlled, phase 3 trial. Lancet. 2011;377:1341.

10Garvey WT et al. Two­year sustained weight loss and metabolic benefits with controlled­release phentermine/topiramate in obese and overweight adults (SEQUEL): a

randomized, placebo­controlled, phase 3 extension study. Am J Clin Nutr. 2012;95:297.

11Contrave [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2014.

12Greenway FL et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR­I): a multicentre, randomised, double­blind, placebo­controlled,

phase 3 trial. Lancet. 2010;376:595.

13Apovian CM et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity­related risk factors (COR­II). Obesity (Silver Spring). 2013;21:935.

14Wadden TA et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR­BMOD trial. Obesity (Silver Spring).

2011;19:110.

15Hollander P et al. Effects of naltrexone sustained­release/bupropion sustained­release combination therapy on body weight and glycemic parameters in overweight and

obese patients with type 2 diabetes. Diabetes Care. 2013;36:4022.

16Saxenda [package insert]. Plainsboro, NJ: Novo Nordisk; 2014.

17Pi­Sunyer X et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11.

18Davies MJ et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes randomized clinical trial. JAMA. 2015;314:687.

19Wadden TA et al. Weight maintenance and additional weight loss with liraglutide after low­calorie­diet induced weight loss: the SCALE Maintenance randomized study. Int J

Obes (Lond). 2013;37:1443.

GLP­1, glucagon­like peptide­1; MEN2, multiple endocrine neoplasia syndrome type 2; MTC, medullary thyroid carcinoma.

Reproduced with permission from Saunders KH et al. Obesity pharmacotherapy. Med Clin North Am. 2018;102:135.

20Wilding JPH et al. Once­weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989.

21Davies M et al. STEP 2 Study Group. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double­blind, double­

dummy, placebo­controlled, phase 3 trial. Lancet. 2021;397(10278):971.

22Wadden TA et al; STEP 3 Investigators. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight

or obesity: The STEP 3 randomized clinical trial. JAMA. 2021;325:1403.

23Rubino D et al. Supplement to: Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4

randomized clinical trial. JAMA. 2021;325:1414.

Liraglutide 3.0 mg daily and semaglutide 2.4 mg weekly are subcutaneous injectable glucagon­like peptide­1 (GLP­1) receptor agonists approved by the
FDA for the treatment of obesity. GLP­1 is a hormone released by GI L­cells in response to a meal that delays gastric emptying, stimulates glucose­dependent
insulin secretion, and reduces food intake. Liraglutide 1.8 mg and semaglutide 2.0 mg are FDA­approved for the treatment of type 2 diabetes and cardiovascular
risk reduction in patients with type 2 diabetes. Liraglutide 3.0 mg was approved by the FDA for weight loss in 2014. It is initiated at a dose of 0.6 mg subcutaneously
daily and increased by 0.6 mg each week to a maximum of 3.0 mg subcutaneously daily. In a 2022 meta­analysis of 8 RCTs, liraglutide 3.0 mg is associated with
4.81% greater total body weight loss than placebo. In 2021, semaglutide 2.4 mg was FDA­approved for the treatment of obesity. It is initiated at a dose of 0.25 mg
subcutaneously weekly and titrated to a maximum dose of 2.4 mg weekly. In a 2022 meta­analysis of eight RCTs, semaglutide is associated with a 10.76% greater
mean total body weight loss than placebo. In light of its greater efficacy in reducing total body weight, a 2022 American Gastroenterological Association (AGA)
guideline endorses the use of semaglutide over other antiobesity medications. Both agents may cause nausea, vomiting, constipation, or diarrhea, and a small
increase in pancreatitis and cholecystitis. There is a boxed warning that both liraglutide and semaglutide may cause thyroid C­cell tumors (including medullary
thyroid carcinoma) in rodents. There is no evidence that GLP­1 receptor agonists cause C­cell tumors in humans.

Phentermine is the most commonly prescribed adrenergic agonist and antiobesity medication in the United States; other adrenergic agonists include
diethylpropion, benzphetamine, and phendimetrazine. In a 28­week controlled trial, participants taking phentermine 15 mg daily lost an average of 6.0 kg
compared with 1.5 kg among those assigned to placebo. In a 2022 AGA meta­analysis of seven short­term RCTs, phentermine was associated with 3.63% greater
total body weight loss than placebo. The maximum recommended dosage of phentermine is 37.5 mg daily, but the dosage should be individualized to the lowest
effective dose. Phentermine is indicated for short­term use (3 months), as there are no long­term trials of phentermine monotherapy; but it was approved in
Downloaded 2025­1­21 9:1 P Your IP is
combination withKatherine
31­04: Obesity, topiramateH.
ERSaunders;
for long­term therapy.
Leon I. IgelSince obesity is a chronic disease, many providers prescribe phentermine for greater than 3 months
Page 8as off­
/ 11
label therapy for ongoing weight management depending on individual state restrictions.
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The combination of phentermine and topiramate ER (3.75 mg/23 mg orally daily for 14 days, then 7.5 mg/46 mg orally daily, to a maximum dosage of 15 mg/92
thyroid carcinoma) in rodents. There is no evidence that GLP­1 receptor agonists cause C­cell tumors in humans.
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Phentermine is the most commonly prescribed adrenergic agonist and antiobesity medication in the United States; other adrenergic agonists include
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diethylpropion, benzphetamine, and phendimetrazine. In a 28­week controlled trial, participants taking phentermine 15 mg daily lost an average of 6.0 kg
compared with 1.5 kg among those assigned to placebo. In a 2022 AGA meta­analysis of seven short­term RCTs, phentermine was associated with 3.63% greater
total body weight loss than placebo. The maximum recommended dosage of phentermine is 37.5 mg daily, but the dosage should be individualized to the lowest
effective dose. Phentermine is indicated for short­term use (3 months), as there are no long­term trials of phentermine monotherapy; but it was approved in
combination with topiramate ER for long­term therapy. Since obesity is a chronic disease, many providers prescribe phentermine for greater than 3 months as off­
label therapy for ongoing weight management depending on individual state restrictions.

The combination of phentermine and topiramate ER (3.75 mg/23 mg orally daily for 14 days, then 7.5 mg/46 mg orally daily, to a maximum dosage of 15 mg/92
mg orally daily) targets two different weight­regulation mechanisms simultaneously. In a 56­week clinical trial, participants taking 15/92 mg lost significantly more
weight (9.8%) than those assigned to 7.5/46 mg (7.8%) or placebo (1.2%). A 2022 AGA meta­analysis of three RCTs with 52–56 weeks of follow­up found that
phentermine­topiramate resulted in 8.45% greater total body weight loss than placebo. There is a potential increased risk of orofacial clefts in infants exposed to
topiramate during the first trimester of pregnancy.

The combination of naltrexone SR and bupropion SR (8 mg/90 mg, increasing from 1 tablet orally daily by 1 additional daily tablet each week to a maximum of
2 tablets twice daily) reduces both appetite and food cravings by targeting two areas of the brain: the arcuate nucleus of the hypothalamus and the mesolimbic
dopamine reward circuit. Naltrexone 32 mg/bupropion 360 mg is associated with a 6.1% reduction in body weight compared to 1.3% with placebo after 56 weeks.
As with all antidepressants, bupropion carries a black box warning related to a potential increase in suicidality among patients under age 24 years during the early
phase of treatment.

Orlistat works in the GI tract to inhibit intestinal lipase, thus reducing dietary fat absorption. Orlistat may thereby cause steatorrhea, fecal urgency, abdominal
discomfort, and reduced absorption of fat­soluble vitamins. An AGA meta­analysis of RCTs found that individuals taking orlistat lost 2.8% more total body weight
compared with placebo. The recommended dose is 120 mg (Xenical, prescription­strength) or 60 mg (Alli, over­the­counter) three times per day with each main
meal containing fat. A 2022 AGA guideline suggests against the use of orlistat due to the small magnitude of weight loss and the moderate rate of discontinuation
due to side effects.

Bariatric surgery is the most effective treatment for obesity. It is associated with significant and sustained weight loss, reduction or resolution of obesity­related
comorbidities, and improved quality of life. Bariatric surgery is associated with lower incidence of cardiovascular events, decreased number of cardiovascular
deaths, and reduced overall mortality compared to usual care. The two most common bariatric procedures in the United States are the sleeve gastrectomy and the
Roux­en­Y gastric bypass. The laparoscopic adjustable gastric band and other bariatric surgical procedures are performed less frequently. Bariatric surgery can
be considered in patients with a BMI of 40 or higher or with a BMI of 35 or higher with at least one obesity­related complication who failed to achieve sufficient
weight loss following lifestyle modification, with or without antiobesity medication. Long­term medical follow­up, lifestyle changes, and adherence to a vitamin
regimen are crucial to the success of bariatric surgery. Some patients have difficulty maintaining weight loss and regain some portion of the lost weight.
Contraindications include poor cardiac reserve, COPD or respiratory dysfunction, severe psychological disorders, and nonadherence to medical treatment.
Despite the known benefits of bariatric surgery, less than 1% of eligible patients undergo a weight­loss surgery. This is likely due to limited patient knowledge of
the health benefits of surgery, limited provider comfort in recommending surgery, and inadequate insurance coverage.

Sleeve gastrectomy involves removing approximately 70% of the stomach body and antrum along the greater curvature. The pyloric sphincter and the small
intestine remain intact. The fundus of the stomach, which secretes ghrelin, a hormone that stimulates appetite, is also removed. Sleeve gastrectomy is associated
with approximately 25% total body weight loss after 1 year. Because this procedure is mainly restrictive (versus the Roux­en­Y gastric bypass, which is also
malabsorptive), there is a lower risk of nutritional deficiencies. In general, sleeve gastrectomy is associated with fewer complications than the Roux­en­Y gastric
bypass. Early adverse events include bleeding, leakage along the staple line, stenosis, and vomiting. Late complications include gastroesophageal reflux,
nutritional deficiencies, and stomach expansion, leading to decreased restriction. Unlike Roux­en­Y gastric bypass, sleeve gastrectomy is not reversible.

The Roux­en­Y gastric bypass involves a staple partition across the proximal stomach with attachment of a small proximal stomach to a jejunal limb, thus
bypassing the remainder of the stomach, duodenum, and the proximal jejunum. Roux­en­Y gastric bypass is associated with approximately 30% total body weight
loss at 1 year and greater improvements in comorbid disease markers compared to the sleeve gastrectomy. Roux­en­Y gastric bypass is associated with a lower
rate of gastroesophageal reflux than sleeve gastrectomy and can even alleviate gastroesophageal reflux in patients who have it. It is often recommended over
sleeve gastrectomy for patients with type 2 diabetes because it leads to greater long­term remission; however, both procedures have low efficacy for type 2
diabetes remission among patients with limited pancreatic beta cell reserve. Early adverse events associated with Roux­en­Y gastric bypass include obstruction,
stricture, leak, and failure of the staple partition of the upper stomach. Late adverse events include nutritional deficiencies (eg, vitamins B1, B12, D, and iron) and
anastomosis ulceration. Dumping syndrome can develop at any time. Roux­en­Y gastric bypass is technically a reversible procedure; however, it is generally only
reversed in extreme circumstances.

The laparoscopic adjustable gastric band is an inflatable device that is placed around the fundus of the stomach to create a small pouch. The size of the
pouch can be adjusted to regulate food intake by increasing or decreasing the amount of saline in the band. This procedure is associated with 15–20% total body
weight loss at 1 year. As the procedure is purely restrictive, there is a lower risk of nutritional deficiencies compared to Roux­en­Y gastric bypass. Laparoscopic
adjustable gastric band is reversible and less invasive than the other two procedures, but it is associated with more complications and less weight loss than sleeve
gastrectomy and Roux­en­Y gastric bypass. As a result, the band only accounts for 1% of bariatric procedures performed in the United States, and many bands are
ultimately removed due to complications. The most common adverse events include nausea, vomiting, obstruction, band erosion or migration, and esophageal
Downloaded 2025­1­21 9:1 P Your IP is
dysmotility leading
31­04: Obesity, to acid reflux.
Katherine In 2011, the
H. Saunders; FDA I.
Leon expanded
Igel approval of adjustable gastric bands to patients with a BMI between 30–40 and one weight­related
Page 9 / 11
medical condition.
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Patients who cannot achieve clinically meaningful weight loss with antiobesity medications and who do not undergo bariatric surgery fall into a “treatment gap.”
The laparoscopic adjustable gastric band is an inflatable device that is placed around the fundus of the stomach to create a small pouch. The size of the
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pouch can be adjusted to regulate food intake by increasing or decreasing the amount of saline in the band. This procedure is associated with 15–20% total body
Access Provided by:
weight loss at 1 year. As the procedure is purely restrictive, there is a lower risk of nutritional deficiencies compared to Roux­en­Y gastric bypass. Laparoscopic
adjustable gastric band is reversible and less invasive than the other two procedures, but it is associated with more complications and less weight loss than sleeve
gastrectomy and Roux­en­Y gastric bypass. As a result, the band only accounts for 1% of bariatric procedures performed in the United States, and many bands are
ultimately removed due to complications. The most common adverse events include nausea, vomiting, obstruction, band erosion or migration, and esophageal
dysmotility leading to acid reflux. In 2011, the FDA expanded approval of adjustable gastric bands to patients with a BMI between 30–40 and one weight­related
medical condition.

Patients who cannot achieve clinically meaningful weight loss with antiobesity medications and who do not undergo bariatric surgery fall into a “treatment gap.”
Several devices and endoscopic procedures are available that are reversible and minimally invasive. In addition, they may be less expensive and safer than
bariatric surgery for poor surgical candidates. The five FDA­approved devices include two intragastric balloons (Orbera and Obalon), the AspireAssist aspiration
device, superabsorbent hydrogel capsules (Plenity), and the TransPyloric Shuttle. The endoscopic sleeve gastroplasty is a newer option that uses an endoscopic
suturing device to reduce the cavity of the stomach, mimicking the surgical sleeve gastrectomy without the need for surgical resection. In a propensity score­
matched study of 3018 patient­pairs conducted at a surgical weight loss center, total body weight loss at 3 years was 19% following surgical sleeve gastrectomy
versus 14% following endoscopic sleeve gastroplasty.

WHEN TO REFER
Patients with a BMI greater than or equal to 30 or a BMI greater than or equal to 27 with at least one weight­related comorbid condition may be referred to an
obesity medicine specialist.

Patients with a BMI greater than or equal to 40 (or greater than or equal to 35 with at least one obesity­related comorbid condition) who have not achieved
sufficient weight loss to address health goals following behavioral treatment, with or without antiobesity medication, may be referred to a bariatric surgeon.

Alqahtani AR et al. Endoscopic gastroplasty versus laparoscopic sleeve gastrectomy: a noninferiority propensity­matched comparative study. Gastrointest
Endosc 2022;96:44.
[PubMed: 35248571]

Arterburn DE et al. Benefits and risks of bariatric surgery in adults: a review. JAMA. 2020;324:879.
[PubMed: 32870301]

Bray GA et al. Evidence­based weight loss interventions: individualized treatment options to maximize patient outcomes. Diabetes Obes Metab. 2021;23(Suppl
1):50.
[PubMed: 32969147]

Carlsson LMS et al. Life expectancy after bariatric surgery in the Swedish Obese Subjects study. N Engl J Med. 2020;383:1535.
[PubMed: 33053284]

Doumouras AG et al. Association between bariatric surgery and all­cause mortality: a population­based matched cohort study in a universal health care system.
Ann Intern Med. 2020;173:694.
[PubMed: 32805135]

Grönroos S et al. Effect of laparoscopic sleeve gastrectomy vs Roux­en­Y gastric bypass on weight loss and quality of life at 7 years in patients with morbid
obesity: the SLEEVEPASS randomized clinical trial. JAMA Surg. 2021;156:137.
[PubMed: 33295955]

Grunvald E et al. AGA clinical practice guideline on pharmacological interventions for adults with obesity. Gastroenterology. 2022;163:1198.
[PubMed: 36273831]

Hedjoudje A et al. Efficacy and safety of endoscopic sleeve gastroplasty: a systematic review and meta­analysis. Clin Gastroenterol Hepatol. 2020;18:1043.
[PubMed: 31442601]

Istfan NW et al. Approach to the patient: management of the post­bariatric surgery patient with weight regain. J Clin Endocrinol Metab. 2021;106:251.
[PubMed: 33119080]

Lee Y et al. Laparoscopic sleeve gastrectomy versus laparoscopic Roux­en­Y gastric bypass: a systematic review and meta­analysis of weight loss, comorbidities,
and biochemical outcomes from randomized controlled trials. Ann Surg. 2021;273:66.
[PubMed: 31693504]

Sharaiha RZ et
Downloaded al. Five­year
2025­1­21 9:1outcomes
P Your of
IPendoscopic
is sleeve gastroplasty for the treatment of obesity. Clin Gastroenterol Hepatol. 2021;19:1051.
[PubMed:
31­04: 33011292]
Obesity, Katherine H. Saunders; Leon I. Igel Page 10 / 11
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Shi Q et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta­analysis of randomised controlled trials. Lancet.
2022;399:259.
[PubMed: 33119080]
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Lee Y et al. Laparoscopic sleeve gastrectomy versus laparoscopic Roux­en­Y gastric bypass: a systematic review and meta­analysis of weight loss, comorbidities,
Access Provided by:
and biochemical outcomes from randomized controlled trials. Ann Surg. 2021;273:66.
[PubMed: 31693504]

Sharaiha RZ et al. Five­year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Clin Gastroenterol Hepatol. 2021;19:1051.
[PubMed: 33011292]

Shi Q et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta­analysis of randomised controlled trials. Lancet.
2022;399:259.
[PubMed: 34895470]

Tchang BG, Saunders KH, Igel LI. Best practices in the management of overweight and obesity. Med Clin North Am. 2021;105:149.
[PubMed: 33246516]

Tchang BG et al. An update on pharmacotherapeutic strategies for obesity. Expert Opin Pharmacother. 2021;22:1305.
[PubMed: 33599159]

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31­04: Obesity, Katherine H. Saunders; Leon I. Igel Page 11 / 11
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 CURSO PM ENDOCRINO REPRODUCTOR EXCRETOR
PRÁCTICA DE SIMULACOÓN
SEMANA 1

LOGRO DEL APRENDIZAJE

Al finalizar la sesión, el estudiante realiza la evaluación de las medidas antropométricas: peso, talla y perímetro abdominal

HABILIDAD 1
1. El docente demuestra la técnica de medición del peso
2. Los estudiantes realizan por pares la técnica de medición del peso
3. El docente verifica con la lista de chequeo la técnica de medición del peso y realiza retroalimentación

LISTA DE CHEQUEO: PESO

INDICACIONES: Antes de iniciar el procedimiento verifica la ubicación y condiciones de la balanza. La balanza debe
estar ubicada sobre una superficie lisa, horizontal y plana, sin desnivel o presencia de algún objeto extraño bajo la
misma, y con buena iluminación.

PASOS ACTIVIDAD REALIZÓ NO REALIZÓ COMENTARIO

Saluda a la paciente, le informa y solicita consentimiento
1 sobre el procedimiento a realizar
2 Lavado de manos antes del procedimiento.
Solicita a la persona que se quite los zapatos y el exceso de
3 ropa para poderla pesar
Ajusta la balanza a “0” (cero) antes de realizar la toma de
4 peso

Solicita a la persona se coloque en el centro de la plataforma

de la balanza, en posición erguida y relajada, de espalda a la
balanza, con la mirada fija en plano horizontal, con los
brazos extendidos a los lados, las palmas descansando
sobre los muslos, talones ligeramente separados, los pies
separados formando una “V“ y sin moverse. El extremo
común de ambas varillas queda arriba.
5

Calcula el peso de la ropa que descontará posteriormente.

6

Desliza la pesa mayor correspondiente a kilogramos hacia la

derecha hasta que el extremo común de ambas varillas
quede abajo y no se mueva, luego retroceder una medida de
diez kilogramos, ahora el extremo común de ambas varillas
vuelve a quedar arriba. La pesa menor correspondiente a
gramos debe estar ubicado al extremo izquierdo de la varilla .
7
Desliza la pesa menor correspondiente a gramos hacia la
derecha, hasta que el extremo común de ambas varillas se
mantenga en equilibrio en la parte central de la abertura que
8 lo contiene.
Lee el peso en kilogramos, la fracción en gramos y
descuenta el peso de las prendas con la que se le pesó a la
9 persona.
Registra el peso obtenido en kilogramos y con la fracción que
10 corresponda a 100 g, con letra clara y legible.
11 Informa resultados al paciente
12 Lavado de manos despues del procedimiento.

HABILIDAD 2
1. El docente demuestra la técnica de medición de la talla
2. Los estudiantes realizan por pares la técnica de medición de la talla
3. El docente verifica con la lista de chequeo la técnica de medición de la talla y realiza retroalimentación

LISTA DE CHEQUEO: TALLA

INDICACIONES: Antes de iniciar el procedimiento debe verificar la ubicación y condiciones del tallímetro, que el
tope móvil se deslice suavemente y chequear las condiciones de la cinta métrica a fin de dar una lectura correcta.
Si el evaluador es de menor talla que la persona que está midiendo, se recomienda el uso de la escalinata
de dos peldaños para una adecuada medición de la talla.
 PASOS ACTIVIDAD REALIZÓ NO REALIZÓ COMENTARIO
Saluda a la paciente, le informa y solicita consentimiento
1 sobre el procedimiento a realizar
2 Lavado de manos antes del procedimiento.
Solicita que se quite los zapatos, exceso de ropa y los
accesorios u otros objetos que interfieran con la medición
3
Indica que se ubique en el centro de la base del tallímetro, de
espaldas al tablero, en posición erguida, mirando al frente,
con los brazos a los costados del cuerpo, con las manos
descansando sobre los muslos, los talones juntos y las
puntas de los pies ligeramente separados
4
Asegura que los talones, pantorrillas, nalgas, hombros y
parte posterior de la cabeza se encuentren en contacto con
5 el tablero del tallímetro.
Verifica la posición de la cabeza: constata que la línea
horizontal imaginaria que sale del borde superior del
conducto auditivo externo hacia la base de la órbita del ojo,
se encuentre perpendicular al tablero del tallímetro (Plano de
6 Frankfurt).
Coloca la palma abierta de su mano izquierda sobre el
mentón de la persona que se está midiendo, luego ir
cerrándola de manera suave y gradual sin cubrir la boca, con
la finalidad de asegurar la posición correcta de la cabeza
7 sobre el tallímetro
Con la mano derecha, desliza el tope móvil hasta hacer
contacto con la superficie superior de la cabeza (vértex
craneal), comprimiendo ligeramente el cabello; luego deslizar
el tope móvil hacia arriba. Este procedimiento (medición)
debe ser realizado tres veces en forma consecutiva,
acercando y alejando el tope móvil. Cada procedimiento
8
tiene un valor en metros, centímetros y milímetros.
Lee y registra las tres medidas obtenidas, obtiene el
promedio y lo registra en la historia clínica con una
aproximación de 0,1 cm. Si la medida cae entre dos mm se
9 debe registrar el milímetro inferior
10 Lavado de manos despues del procedimiento.
11 Informa resultados al paciente

HABILIDAD 3
1. El docente demuestra la técnica de medición del perímetro abdominal
2. Los estudiantes realizan por pares la técnica de medición del perímetro abdominal
3. El docente verifica con la lista de chequeo la técnica de medición del perímetro abdominal y realiza retroalimentación

LISTA DE CHEQUEO: PERÍMETRO ABDOMINAL

PASOS ACTIVIDAD REALIZÓ NO REALIZÓ COMENTARIO

Saluda a la paciente, le informa y solicita consentimiento
1 sobre el procedimiento a realizar
2 Lavado de manos antes del procedimiento.
Solicita al paciente que se ubique en posición erguida, sobre
una superficie plana, con el torso descubierto, con los
brazos relajados y paralelos al tronco y que se desabroche el
cinturón o correa que pueda comprimir el abdomen.
3
Solicita al paciente que los pies deben estar separados por
una distancia de 25 a 30 cm, de tal manera que su peso se
4 distribuya sobre ambos miembros inferiores.
Sobre la linea axilar media, palpa el borde inferior de la
última costilla y el borde superior de la cresta iliaca, ambos
del lado derecho, determine la distancia media entre ambos
puntos y proceda a marcarlo; realizar este mismo
5 procedimiento para el lado izquierdo
Coloque la cinta métrica horizontalmente alrededor del
abdomen, tomando como referencia las marcas de las
distancias medias de cada lado, sin comprimir el abdomen
6 de la persona.
Realice la lectura en el punto donde se cruzan los extremos
de la cinta métrica teniendo cuidado de no colocar el dedo
entre la cinta métrica y la piel del paciente
7
 Tome la medida en el momento en que la persona respira
lentamente y expulsa el aire (al final de una exhalación
normal). Este procedimiento debe ser realizado tres veces en
forma consecutiva, acercando y alejando la cinta, tomando la
medida en cada una de ellas.
8
Lee y registra las tres medidas obtenidas, obtiene el
promedio y lo registra en la historia clínica con una
aproximación de 0,1 cm. Si la medida cae entre dos mm se
9 debe registrar el milímetro inferior
10 Lavado de manos despues del procedimiento.
11 Informa resultados al paciente

&
SINDROME DE INFECCIÓN CERVICAL (CERVICITIS)

· Chlamydia trachomatis y
Neisseris gonorrhoese

o
flujo mucopurulento cervical ,
friabilidad cervical cérvix ,
en fresa , flujo vaginal , disparenia, disuris

SINDROME DE DESCARGA URETRAL

N (.trachomatis Mycoplasma genitalum Ureaplasma urealiticum Trichomona raginalis

· .

gonorrhoese , , , ,

Disuria, irritación la uretra distal mento urinario acompañada o no de evitema secreción cretral .
· en o
y

SINDROME DE ÚLCERA GENITAL

· Treponems pallidum ,
H ducreyi
.

Chlamydia trachomatis , Kleibsella granulomatis ,

VAS
,

· Lesiones genitales ulcerativas ,

erosivas , postulares o resiculares acompañadas o no con linfadenopatia regional .

SINDROME DE FLUJO VAGINAL

o
Vaginosis bacteriana ,
candidiasis y Tricomoniasis

· Descarga raginal fétida ,

flujo de color amarillo y prurito vaginal o vulvar ,
eritems vaginal o vulvar , disuris

SINDROME DE INFLAMACIÓN ESCROTAL

o pididimitis :
complicación de la infección por Chlamydis trachomatis o N gonorrhoeae
.

·
Tumefacción o dolor testicular unilateral ,
con o sin descarga vretral , aumento de la temperatura local

SINDROME DE BUBÓN INGUINAL

o
LGV((trachomatis) y
chancroide (H .

ducreyi)

ol o pápulas o úlceras en región inguinal las ,

cuales se acompañan de linfadenopatías llamadas bubones
Cribado con antígeno prostático específico
Prueba de PSA: para los hombres que eligen la prueba de detección de
cáncer de próstata, sugerimos la prueba solo con una prueba de sangre de
PSA. El examen rectal digital (DRE, por sus siglas en inglés) generalmente no
se usa como prueba de detección para el cáncer de próstata, ya sea solo o en
combinación con una prueba de PSA.
Los estudios han estimado que las elevaciones del PSA pueden preceder a las
manifestaciones clínicas del cáncer de próstata entre 5 y 10 años o más
[ 25,50,51 ].
Sin embargo, el PSA también puede estar elevado en ausencia de cáncer de
próstata en hombres con condiciones benignas en curso (p. ej., hiperplasia
prostática benigna [HPB]) o condiciones transitorias (p. ej., prostatitis)
Razones para diferir temporalmente la prueba de PSA — Ciertos factores
pueden elevar transitoriamente el PSA lo suficiente como para afectar su
desempeño como prueba de detección. En presencia de cualquiera de estos
factores, es apropiado aplazar temporalmente la detección de PSA el tiempo
suficiente para que se resuelva una elevación transitoria de PSA [ 52 ]:
● Síntomas que sugieren prostatitis bacteriana; aplazar la prueba de PSA
hasta seis u ocho semanas después de que desaparezcan los síntomas
● retención urinaria aguda o instrumentación uretral; aplazar la prueba de
PSA durante al menos dos semanas
● Biopsia de próstata reciente o resección transuretral de la próstata
(TURP); aplazar la prueba de PSA durante al menos seis semanas
Además, un paciente que está repitiendo una prueba de PSA para evaluar un
resultado cercano a un punto de corte que podría impulsar una evaluación
urológica debe abstenerse durante al menos 48 horas de actividades que
puedan aumentar transitoriamente los niveles de PSA (p. ej., eyaculación o
andar en bicicleta).
Si se realizó un DRE, el PSA se puede medir inmediatamente después porque
el DRE produce solo elevaciones transitorias mínimas del PSA de 0,26 a 0,4
ng/mL [ 53,54 ].
En los hombres con hipertrofia prostática benigna sintomática, no es necesario
posponer la medición del PSA mientras se administra el tratamiento para
mejorar los síntomas de la BPH, a menos que el paciente se haya sometido a
una RTUP en las últimas seis semanas.
Interrupción de las pruebas de detección : existe un acuerdo general sobre
no realizar pruebas de detección a los hombres que tienen comorbilidades
sustanciales que limitan la esperanza de vida a menos de 10 años. Hay menos
consenso sobre la edad precisa a la que interrumpir el cribado.
● Esperanza de vida : no evaluamos a los hombres para el cáncer de
próstata que tienen una esperanza de vida de <10 años. Es poco
probable que la detección beneficie a estos hombres dado el curso
generalmente indolente del cáncer de próstata.
Las pautas de sociedades profesionales generalmente recomiendan no
evaluar a hombres que tienen menos de 10 años [ 31,34 ] o 10 a 15 años
[ 33,49 ] de esperanza de vida.
● Edad : para los hombres con una expectativa de vida de al menos 10
años, la mayoría de los médicos ofrecen exámenes de detección hasta
los 70 años; algunos pueden continuar el cribado hasta los 75 años si el
paciente lo desea. Entre las pautas, la edad sugerida para interrumpir la
detección del cáncer de próstata varía de 69 a 75 años
[ 7,33,35,36,43,49 ]. Las tablas actuariales sugieren que entre los
hombres con una salud promedio, solo aquellos de 75 años o menos
tienen una expectativa de vida de 10 años.
Otros datos sugieren que puede ser apropiado suspender la detección en
personas de hasta 65 años. Un análisis encontró que suspender la
prueba de PSA a los 65 años para hombres con niveles de PSA de 0,5
ng/mL o menos aún identificaría todos los cánceres que se habrían
detectado a los 75 años [ 65 ]. Además, un análisis de decisión que utilizó
datos de Medicare encontró que el tratamiento agresivo del cáncer de
próstata en hombres de 70 años o más disminuiría la esperanza de vida
ajustada por calidad [ 66 ].
INTERPRETACIÓN Y SEGUIMIENTO DE RESULTADOS
Interpretación de PSA: usamos un valor de PSA de ≥4,0 ng/mL en una
prueba de detección (después de aplicar un factor de corrección de 2,0 al
resultado de PSA si el paciente está usando un ARI) para determinar si se
justifica una evaluación adicional para el cáncer de próstata.
Un PSA de ≥4,0 ng/mL ha sido el estándar más ampliamente aceptado para
equilibrar las compensaciones entre sensibilidad y especificidad. Sin embargo,
no existe un valor único de PSA que evite pasar por alto cánceres importantes
en una etapa curable, evite los falsos positivos y la detección de enfermedades
clínicamente insignificantes, y evite someter a los hombres a biopsias de
próstata innecesarias. Una revisión sistemática estimó que el límite de PSA de
4,0 ng/mL tenía una sensibilidad del 21 % con una especificidad del 91 % para
la detección de cualquier cáncer de próstata; para la detección de un cáncer de
alto grado, la sensibilidad fue del 51 por ciento [ 31]. La baja sensibilidad
significa que algunos hombres con niveles de PSA <4 ng/mL tendrán cáncer de
próstata. En el PCPT, se encontró que el 15,2 por ciento de los hombres con
niveles de PSA <4 ng/mL anualmente durante siete años tenían cáncer de
próstata en la biopsia al final del estudio; el 1,6 % tenía cáncer de próstata de
alto grado [ 69 ].
Reducir el límite de PSA mejora un poco la sensibilidad de la prueba. Un punto
de corte de PSA de 3,0 ng/mL tuvo una sensibilidad del 32 por ciento para la
detección de cualquier cáncer de próstata; para la detección de un cáncer de
alto grado, la sensibilidad fue del 68 por ciento [ 31 ]. Entre aquellos con PSA
entre 2,1 y 4,0 ng/mL, se encontró cáncer de próstata en el 24,7 por ciento (167
de 675 hombres) y el 3,5 por ciento (cuatro hombres) tenían cánceres de alto
grado. Incluso un límite de PSA tan bajo como 1,1 ng/mL habría pasado por
alto el 17 % de los cánceres, incluido el 5 % de los cánceres de alto grado
[ 70 ].
Sin embargo, la reducción del límite de PSA empeora la especificidad y el
sobrediagnóstico. Un límite de PSA de 3,0 ng/mL tiene una especificidad de
alrededor del 85 % para la detección de cualquier cáncer de próstata [ 31 ]. Se
ha proyectado que si el límite de PSA se redujera a 2,5 ng/mL, la cantidad de
hombres cuyo PSA se define como anormal se duplicaría hasta seis millones
en los Estados Unidos [ 71 ]. Además, es posible que muchos de los cánceres
que se detectarían con estos niveles más bajos de PSA nunca se hayan vuelto
clínicamente evidentes, por lo que detectarlos usando un punto de corte de
PSA más bajo conduciría a un sobrediagnóstico y un sobretratamiento
Elevar el valor de corte de PSA aumenta el valor predictivo positivo (VPP) para
el cáncer de próstata, pero reduce la probabilidad de que el cáncer esté
confinado al órgano y, por lo tanto, sea potencialmente curable. Para cualquier
PSA >4,0 ng/mL, el VPP general para el cáncer de próstata es de
aproximadamente el 30 % [ 31 ]. Sin embargo, para un PSA de 4,0 a 10,0
ng/mL, un poco por encima del límite, el VPP es aproximadamente del 25 % y
casi el 75 % de los cánceres están limitados al órgano [ 73 ]. Con un punto de
corte más alto de PSA >10 ng/mL, el PPV aumenta del 42 al 64 por ciento, pero
menos del 50 por ciento de los cánceres están limitados al órgano.
Algunos expertos usan rangos de referencia específicos de la edad para el
PSA, en lugar de usar el mismo punto de corte para todas las edades. Los
niveles de PSA generalmente aumentan con la edad, en parte porque los
hombres mayores son más propensos a tener una próstata agrandada benigna
que produce mayores cantidades de PSA. Sin embargo, hay datos limitados
para respaldar los valores de referencia exactos para las cohortes de edad.
Existen varias limitaciones para determinar la precisión de la prueba de
PSA. La mayoría de los hombres con valores normales de PSA no se han
sometido a una biopsia a menos que hayan tenido un DRE anormal; este sesgo
de evaluación lleva a sobreestimar la sensibilidad y subestimar la especificidad
del PSA para detectar el cáncer de próstata. Otra limitación es la falta de
consenso sobre qué cánceres son clínicamente importantes; El PSA detecta
tanto los cánceres clínicamente poco importantes como los
importantes. Además, la tasa de falsos negativos de la biopsia puede haber
sido tan alta como del 10 al 20 por ciento en estudios con <12 muestras por
biopsia de próstata [ 74,75 ].
Derivación a urología : las indicaciones para una derivación a urología
incluyen:
● PSA ≥4.0 ng/mL – Remitimos a los pacientes para evaluación urológica
si el PSA es ≥4.0 ng/mL. Antes de la remisión, si el PSA está entre 4,0 y
7,0 ng/mL, repetimos la prueba en seis a ocho semanas, porque el PSA
puede elevarse transitoriamente debido a ciertos factores benignos
modificables (y cualquier factor identificado debe abordarse antes de
repetir el PSA). Algunos expertos remiten a los pacientes si el nivel de
PSA es ≥4,0 ng/m sin repetir primero un PSA moderadamente elevado.
● Aumento del PSA durante el tratamiento con inhibidor de la 5-alfa
reductasa : un paciente que toma finasterida o dutasterida para la
hiperplasia prostática benigna (HPB) con un aumento confirmado del nivel
de PSA > 0,5 ng/mL (en cualquier período de tiempo) debe ser
considerado para derivación a urología.
● DRE anormal: aunque no sugerimos DRE para la detección, si se
realiza DRE, los hombres con nódulos, induración o asimetría en el
examen de próstata deben ser derivados a un urólogo para evaluación,
independientemente del nivel sérico de PSA. Sin embargo, el
agrandamiento simétrico y la firmeza de la próstata son frecuentes en
hombres con HBP y, por lo general, no justifican una evaluación urológica
a menos que el PSA esté elevado o haya otras preocupaciones.
La derivación para una evaluación urológica no necesariamente resultará en
una biopsia de próstata. El urólogo puede realizar otras pruebas (p. ej.,
proporción de PSA libre a total [f/T PSA], PCA3, prueba 4Kscore y/o imágenes
por resonancia magnética [IRM]) para ayudar a determinar la probabilidad de
que el PSA esté elevado debido a cáncer de próstata, se puede hacer un
seguimiento del PSA a lo largo del tiempo o se puede realizar una biopsia. Las
consideraciones relevantes incluyen el estado de salud del paciente, la
probabilidad clínica de albergar una enfermedad importante y los deseos
personales.
MÉTODOS NO UTILIZADOS GENERALMENTE PARA TAMIZAJE
Examen rectal digital: sugerimos no realizar un examen rectal digital (DRE,
por sus siglas en inglés) para la detección del cáncer de próstata, ya sea como
un complemento de la prueba del antígeno prostático específico (PSA, por sus
siglas en inglés) o como una prueba independiente.
DRE tiene baja sensibilidad y especificidad para detectar cáncer de
próstata. En un metanálisis, el DRE realizado por médicos de atención primaria
tuvo una sensibilidad estimada del 51 %, una especificidad del 59 % y un valor
predictivo positivo (VPP) global calculado del 41 % [ 76 ]. Sin embargo, la
calidad de la evidencia fue muy baja y hubo heterogeneidad significativa entre
los estudios. Además, se ha descubierto que los urólogos tienen un acuerdo
entre evaluadores relativamente bajo para detectar anomalías prostáticas [ 77 ].
La baja sensibilidad se debe en parte al hecho de que el DRE solo detecta
anomalías palpables en las caras posterior y lateral de la glándula
prostática. Aunque aquí es donde surge la mayoría de los cánceres, otras
áreas de la próstata donde ocurre el cáncer no son accesibles mediante un
examen de los dedos. Además, alrededor de un tercio de los cánceres
detectados por DRE solo están clínica o patológicamente avanzados [ 73,78 ]
en comparación con menos del 10 por ciento detectado por la prueba de PSA
[ 79 ]. Los cánceres de próstata en etapa T1c, la mayoría de los cánceres
detectados por exámenes de detección, no son palpables por definición.
Aunque DRE y PSA son algo complementarios y su uso combinado puede
aumentar la tasa general de detección de cáncer, DRE tiene una utilidad
limitada como prueba complementaria. En un estudio de detección
multicéntrico de 6630 hombres, la tasa de detección de cáncer de próstata fue
del 3,2 % para DRE, del 4,6 % para PSA y del 5,8 % para los dos métodos
combinados [ 73,78 ]. Solo el 18 por ciento de los cánceres fueron detectados
solo por DRE. En otro estudio, el VPP de un DRE sospechoso con un nivel de
PSA normal fue del 10 %, mientras que el VPP de un DRE normal con un nivel
de PSA elevado fue del 24 % [ 80 ]. Entre los hombres con un nivel de PSA
normal, las anomalías en el examen rectal parecían menos probables de un
cáncer si la concentración de PSA estaba por debajo de 1,0 ng/mL que si la
concentración de PSA estaba entre 3,0 y 4,0 ng/mL.
La mayoría de las guías de sociedades especializadas no recomiendan el DRE
para la detección, aunque algunas [ 31,37,43 ] incluyen el DRE para evaluar un
PSA elevado o como una opción junto con la prueba del PSA.
Otras pruebas: no utilizamos de forma rutinaria ninguna otra prueba o
estrategia de interpretación de pruebas para la detección o para decidir qué
hombres derivar para una evaluación urológica por un PSA elevado.
No usamos el cambio absoluto en el PSA ni la velocidad del PSA (es decir, la
tasa de cambio del PSA a lo largo del tiempo) para determinar si derivar a un
paciente que no está tomando un inhibidor de la 5-alfa reductasa (ARI). El PSA
aumenta más rápidamente en hombres con cáncer de próstata que en hombres
sanos. Sin embargo, la velocidad del PSA agrega poca información predictiva
al PSA solo [ 81-87 ].
Se han desarrollado otros métodos para tratar de diferenciar entre los cánceres
de alto riesgo y los cánceres indolentes de bajo riesgo. Sin embargo, la utilidad
clínica de estas estrategias es incierta, no hay consenso sobre el uso de
cualquiera de estas pruebas y se necesitan estudios adicionales para
determinar la efectividad clínica. La guía de la Asociación Americana de
Urología (AUA) señaló la falta de evidencia para el uso de otras pruebas
además del PSA para determinar la necesidad de una derivación para una
biopsia [ 49 ].

Rangos de referencia específicos de la edad : en hombres sin cáncer de

próstata, el PSA sérico refleja la cantidad de epitelio glandular, que a su vez
refleja el tamaño de la próstata. Así, a medida que aumenta el tamaño de la
próstata con la edad, también aumenta la concentración de PSA; aumenta a un
ritmo más rápido en hombres adultos mayores [ 9 ]. En un estudio de 471
hombres, la concentración sérica de PSA aumentó aproximadamente un 3,2 %
(0,04 ng/mL) por año para una persona sana de 60 años [ 10 ]. Como
resultado, diferentes rangos normales de referencia pueden ser apropiados
según la edad de un hombre [ 11,12 ]:
●40 a 49 años – 0 a 2,5 ng/mL
●50 a 59 años – 0 a 3,5 ng/mL
●60 a 69 años – 0 a 4,5 ng/mL
●70 a 79 años – 0 a 6,5 ng/mL
Estos rangos de referencia específicos de la edad se han propuesto como un
medio para mejorar la especificidad y el valor predictivo positivo del PSA sérico
en la detección del cáncer de próstata.
CAUSAS DE UN PSA SÉRICO ELEVADO
Las principales causas de un PSA sérico elevado incluyen:
●Hiperplasia prostática benigna (HPB)
●Cáncer de próstata
●Inflamación/infección prostática
●Trauma perineal

AVANCES EN PRUEBAS DE PSA

Los conceptos emergentes con respecto a las pruebas de PSA que pueden
ayudar a refinar la interpretación de una concentración elevada incluyen:
●Densidad de PSA
●velocidad de PSA
●PSA libre frente a complejo o unido
Presuntamente, estas modificaciones serían más útiles para la detección del
cáncer de próstata cuando el PSA total es de 2,5 a 10,0 ng/mL, el rango en el
que las decisiones sobre pruebas de diagnóstico adicionales son más
difíciles. Sin embargo, en la práctica clínica, el uso de estas técnicas no es
uniforme y sigue siendo objeto de debate.
Densidad de PSA: para compensar más directamente la BPH y el tamaño de
la próstata, se ha utilizado la ecografía transrectal (TRUS) para medir el
volumen de la próstata. Luego, el PSA sérico se divide por el volumen de la
próstata para obtener una densidad de PSA; los valores más altos de densidad
de PSA (superiores a 0,15 ng/mL/cc) son más sugestivos de cáncer de
próstata, mientras que los valores más bajos son más sugestivos de hiperplasia
prostática benigna (HPB) [ 57 ,58 ].
Si bien un estudio inicial sugirió que la densidad de PSA era un método
prometedor para distinguir a los pacientes con enfermedad prostática benigna y
maligna [ 57,59 ], los informes posteriores han encontrado una superposición
considerable en las densidades de PSA entre estos grupos [ 60 ].
Velocidad del PSA : otro enfoque ha sido evaluar la tasa de cambio del PSA
a lo largo del tiempo (la velocidad del PSA). Es más probable que un PSA
sérico elevado que continúa aumentando con el tiempo refleje cáncer de
próstata que uno que se mantiene constantemente estable [ 64 ]. En un
estudio, un límite de velocidad de PSA de 0,75 ng/mL por año distinguió a los
pacientes con cáncer de próstata de aquellos con BPH o sin enfermedad de
próstata con una especificidad del 90 y 100 por ciento, respectivamente
[ 65 ]. Otro estudio del mismo grupo encontró que cuando el PSA era <4 ng/mL,
una velocidad del PSA >0,35 ng/mL por año medida durante varios años se
asoció con un alto riesgo de muerte por cáncer de próstata 15 años después
[ 66].
En la práctica, la utilidad clínica de la velocidad del PSA está limitada en parte
por la variabilidad intrapaciente en el PSA sérico; se deben realizar al menos
tres mediciones consecutivas [ 70].
PSA libre y unido en suero : como se señaló anteriormente, el cáncer de
próstata se asocia con un porcentaje más bajo de PSA libre en el suero en
comparación con las afecciones benignas.
El porcentaje de PSA libre (proporción de PSA libre/total [f/t PSA]) se ha
utilizado para mejorar la sensibilidad de la detección del cáncer cuando el PSA
total está en el rango normal (<4 ng/mL) y para aumentar la especificidad del
cáncer detección cuando el PSA total está en la "zona gris" (4,1 a 10
ng/mL). En este último grupo, cuanto menor sea el valor de f/t PSA, mayor será
la probabilidad de que un PSA elevado represente cáncer y no HPB. Por
ejemplo, en un estudio de hombres con valores de PSA en este rango, la
probabilidad de cáncer en hombres con un PSA af/t inferior al 10 % fue del 56
%, en comparación con solo el 8 % de los hombres con un valor >25 % [ 77 ] .
PSA en complejo : se han desarrollado ensayos para el PSA en complejo
con alfa1-antiquimotripsina (ACT) (cPSA) [ 81-83 ]. En teoría, dicho ensayo
proporcionaría un grado mejorado de especificidad similar al del PSA f/t, pero
solo requeriría la medición de un único análisis. Además de la ventaja
económica obvia, podría evitarse la variabilidad asociada con la falta de
uniformidad de los ensayos de diferentes fabricantes para el PSA total o f/t.
Porcentaje de [-2]proPSA : como se mencionó anteriormente, el PSA se
produce inicialmente como proPSA, y esta forma puede filtrarse
preferentemente en el torrente sanguíneo en hombres con cáncer de
próstata. Una isoforma específica de proPSA es [-2]proPSA, que no se une y
es potencialmente más alta en hombres con cáncer de próstata. El [-2]proPSA
porcentual está aprobado por la Unión Europea para la detección del cáncer de
próstata y está siendo evaluado en los Estados Unidos por la Administración de
Alimentos y Medicamentos.
UPtoDate
Manifestaciones clínicas y evaluación diagnóstica de la
hiperplasia prostática benigna
Autor:
Kevin T. McVary, MD, FACS
Redactor de sección:
Michael P O'Leary, MD, MPH
Redactor adjunto:
Jane Givens, MD, MSCE
Divulgaciones de contribuyentes
Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso
de revisión por pares .
Revisión de la literatura actual hasta: julio de 2022. | Última actualización de este tema: 18 de
noviembre de 2021.

BPH O HPB
LUTS O STUI
INTRODUCCIÓN
La hiperplasia prostática benigna (BPH) es un diagnóstico histológico que se
refiere a la proliferación de tejido epitelial glandular, músculo liso y tejido
conectivo dentro de la zona de transición prostática. La BPH es omnipresente
en los hombres que envejecen, con una prevalencia histológica comprobada
por autopsia en todo el mundo que comienza entre los 40 y los 45 años,
alcanza el 60 % a los 60 años y el 80 % a los 80 años [ 1 ].
La HPB puede ser asintomática, en cuyo caso no requiere tratamiento. Sin
embargo, la HPB puede conducir a un agrandamiento de la próstata
(agrandamiento prostático benigno [BPE]) y provocar síntomas del tracto
urinario inferior (STUI) debido a la obstrucción a nivel del cuello de la vejiga.
Los LUTS pueden ser causados por una variedad de condiciones. En la
discusión a continuación, LUTS/BPH se usará para indicar LUTS atribuidos a
BPH, de acuerdo con las pautas clínicas de BPH de la American Urological
Association (AUA) . Este tema revisará las manifestaciones clínicas y la
evaluación diagnóstica de LUTS/BPH.
TERMINOLOGÍA
El acrónimo BPH (hiperplasia prostática benigna) a menudo se supone
incorrectamente que representa la hipertrofia prostática benigna, que es un
término arcaico que describe un aumento en el tamaño de las células en lugar
del número de células. La BPH produce agrandamiento prostático benigno
(BPE, por sus siglas en inglés) en algunos, pero no en todos los hombres. Este
agrandamiento puede, a su vez, provocar obstrucción prostática benigna (BPO)
y obstrucción de la salida de la vejiga (BOO). Si bien la BPH por sí sola no
requiere tratamiento, la BPE y la BPO a menudo se asocian con síntomas del
tracto urinario inferior (STUI), que pueden requerir tratamiento.
MANIFESTACIONES CLÍNICAS
Presentación clínica: la hiperplasia prostática benigna (HPB) puede ser
asintomática y la correlación entre los síntomas y la presencia de
agrandamiento prostático en el examen físico o en la evaluación
ultrasonográfica transrectal es deficiente.
Cuando es sintomática, la HPB se presenta con síntomas del tracto urinario
inferior (STUI). Las manifestaciones típicas de LUTS/BPH incluyen [ 2 ]:
● Síntomas de almacenamiento (irritativos): frecuencia urinaria, urgencia,
nicturia e incontinencia
● Síntomas de micción: flujo urinario lento, esfuerzo para orinar,
intermitencia urinaria (chorro que comienza y se detiene durante la
micción) o vacilación, división del flujo miccional y goteo terminal
Los síntomas de almacenamiento suelen ser más molestos que los síntomas
de vaciado. La gravedad de los síntomas (la mayoría de las veces clasificada
como leve, moderada o grave) motiva a los pacientes a buscar tratamiento
relacionado con la HPB [ 3 ].
Los hallazgos del examen físico incluyen una próstata agrandada y no dolorosa
en el examen rectal digital (DRE). El tamaño de la próstata en el examen no se
correlaciona bien con la gravedad de los síntomas.
No hay hallazgos típicos de laboratorio o de imágenes, excepto que la BPH
está asociada con niveles más altos de antígeno prostático específico (PSA),
producido por tejido prostático benigno.
Historia natural : los síntomas tienden a progresar gradualmente durante un
período de años, especialmente en pacientes mayores; sin embargo, pueden
mejorar espontáneamente en una minoría de pacientes [ 4-8 ].
La evolución natural de la progresión de STUI/HPB se describió en el Estudio
de seguimiento de profesionales de la salud [ 4 ]. En esta cohorte de 9628
hombres que inicialmente informaron STUI moderados, alrededor de una
cuarta parte progresó a STUI graves durante un seguimiento medio de 5,9
años, y las tasas de progresión aumentaron abruptamente a medida que los
hombres envejecían.
Complicaciones: Las posibles complicaciones de la HPB no tratada incluye la
retención urinaria aguda además, la obstrucción crónica y la imposibilidad de
vaciar completamente la orina de la vejiga pueden aumentar el riesgo de
infecciones del tracto urinario (ITU), cálculos en la vejiga, formación de
divertículos vesicales y daño renal.
La BPH no es un factor de riesgo para el cáncer de próstata. La BPH ocurre
principalmente en la zona central o de transición de la próstata, mientras que el
cáncer de próstata se origina principalmente en la parte periférica de la
glándula. Un análisis del grupo de placebo del Prostate Cancer Prevention
Trial, donde se realizaron biopsias de rutina, no encontró una asociación entre
la HPB y el cáncer de próstata [ 9 ].
DIAGNÓSTICO DIFERENCIAL
Muchas otras condiciones urológicas pueden presentarse con síntomas del
tracto urinario inferior (STUI). Antes de concluir que los STUI están
relacionados con la hiperplasia prostática benigna (HPB), se deben descartar
otros trastornos que pueden causar estos síntomas mediante la anamnesis, la
exploración física y las pruebas de laboratorio y urológicas seleccionadas.
Brevemente, otras causas incluyen:
● Causas urológicas de obstrucción: estenosis uretral, contractura del
cuello de la vejiga y cáncer de próstata.
●Otras afecciones urológicas: infecciones urinarias y cáncer de vejiga.
● Afecciones no urológicas: otras afecciones médicas pueden coexistir
con la HPB y causar un empeoramiento de los síntomas urológicos o
imitar la HPB:
•Enfermedad cardiovascular: la insuficiencia cardíaca, la enfermedad
vascular periférica o la disfunción cardíaca asociada con el edema
periférico pueden empeorar los STUI debido a los cambios de líquido
que inducen la diuresis [ 10 ]. El uso de diuréticos también puede
causar o exacerbar los síntomas urinarios.
•Enfermedad neurológica: los pacientes con enfermedad de Parkinson
o antecedentes de accidente cerebrovascular desarrollan con
frecuencia disfunción miccional. La micción normal requiere una
interacción compleja de la salida de la vejiga, la vejiga y los centros
reguladores de la médula espinal, y los eventos neurológicos pueden
afectar la función y la estabilidad del detrusor. Las condiciones
neurológicas pueden aumentar la complejidad del diagnóstico y
afectar las opciones terapéuticas.
•Enfermedad endocrina: la diabetes mellitus de larga data y mal
controlada conduce a una disminución de la sensación de la vejiga,
disminución de la contractilidad del detrusor y vaciado incompleto de
la vejiga. Además, el aumento de la filtración de glucosa en la orina
conduce a una diuresis osmótica y poliuria obligada, lo que empeora
los STUI debido al aumento de la producción de orina. Reconocer esta
relación común en STUI es fundamental para controlar los síntomas.
•Polidipsia: la diuresis obligada de la polidipsia puede causar síntomas
urinarios que simulan los de STUI/HPB. La información sobre el tipo
de líquido y el momento de la ingesta en relación con el inicio de los
síntomas, el uso de un diario miccional y la ausencia de síntomas
obstructivos son útiles para descubrir esta relación.
EVALUACIÓN
La evaluación de los síntomas del tracto urinario inferior (LUTS)/hiperplasia
prostática benigna (HPB) debe incluir un historial médico detallado y un
examen físico enfocado, que debe incluir un examen neurológico breve, un
examen abdominal y un examen genitourinario, incluido el examen rectal digital
(DRE). Se necesita un pequeño número de pruebas de laboratorio para excluir
otras etiologías.
Los objetivos específicos para el paciente deben definirse como parte de la
evaluación. Si los síntomas no son significativamente molestos o no afectan la
salud del paciente, o si el paciente no quiere tratamiento, no se recomienda
una evaluación adicional. Este enfoque es recomendado por las guías clínicas
de HPB de la American Urological Association (AUA) [ 11,12 ] y es una
prioridad del programa Choosing Wisely de la AUA [ 13 ]. Es poco probable que
estos pacientes experimenten problemas de salud significativos en el futuro
debido a su condición y se les puede volver a ver si es necesario.
Historia: la historia debe incluir la evaluación de los síntomas de
almacenamiento (irritación, frecuencia, urgencia y nicturia) y los síntomas de
vaciado (chorro urinario lento o de fuerza disminuida, esfuerzo para orinar,
intermitencia, vacilación, división del chorro de vaciado) y post-vaciado( goteo
nulo). Esta información es útil para estimar el impacto y la gravedad de los
síntomas iniciales.
Los síntomas de hematuria, incontinencia o retención urinaria deben indicar la
derivación a urología.
Otras características históricas para obtener incluyen:
● Antecedentes de traumatismo uretral, uretritis o instrumentación uretral
que podría provocar estenosis uretral
● Hematuria macroscópica o dolor en la región de la vejiga, que puede
sugerir cálculos o cáncer en la vejiga
● Enfermedad neurológica subyacente, que podría indicar una vejiga
neurogénica
●Fumar cigarrillos, que es un factor de riesgo para el cáncer de vejiga
●Tratamiento con fármacos o agentes de venta libre que pueden alterar la
contractilidad de la vejiga (p. ej., agentes anticolinérgicos) o aumentar la
resistencia al flujo (p. ej., agentes simpaticomiméticos)
●La relación temporal entre el inicio y la gravedad de los STUI y el uso de
medicamentos (es decir, diuréticos para la hipertensión o la insuficiencia
cardíaca congestiva)

Diario miccional: generalmente se obtiene un diario miccional bien llevado o

un gráfico de frecuencia-volumen en pacientes que tienen nicturia como
síntoma predominante, pero también puede ser útil en otros pacientes. Puede
proporcionar información sobre el volumen miccional diario total del paciente, la
frecuencia urinaria diaria, la fracción nocturna de orina miccional y la capacidad
vesical funcional. También proporciona información sobre la ingesta de líquidos,
los episodios de incontinencia, el uso de compresas para la incontinencia y/o la
frecuencia de defecación. Los datos generalmente se registran durante tres
días para crear una muestra más representativa del manejo típico de fluidos
[ 14 ].
En pacientes con nicturia, el diario miccional puede proporcionar evidencia de
poliuria nocturna, que ocurre cuando >33% de la diuresis diaria se expulsa
durante las horas nocturnas. La poliuria nocturna debe impulsar la búsqueda de
causas secundarias y se analiza en detalle en otra parte.
Examen físico: el examen físico debe incluir DRE además de la evaluación
del abdomen, la pelvis y el perineo. Se debe realizar una evaluación motora y
sensorial de la pelvis y miembros inferiores. Dada la complejidad de la
interacción motora y neurológica involucrada en la salud pélvica y el
mantenimiento de la vejiga, cualquier hallazgo anormal debe generar una
investigación adicional. Está indicado un examen neurológico más extenso
para pacientes con posible disfunción neurogénica del tracto urinario inferior.
Se debe realizar un DRE para estimar el tamaño de la próstata. Una próstata
normal tiene aproximadamente el tamaño de una nuez (entre 7 y 16 gramos,
con un promedio de 11 gramos) y es firme y no sensible. Aunque el DRE no es
una herramienta precisa para medir el volumen de la próstata [ 15-17 ], los
exámenes seriados son útiles para seguir el tamaño de la próstata y el examen
puede identificar otras anomalías:
 ● Una glándula prostática exquisitamente sensible puede reflejar la
presencia de prostatitis.
●La presencia de asimetría o nódulos hace sospechar malignidad
● La presencia de disminución del tono del esfínter o ausencia de
sensibilidad perineal puede sugerir una etiología neurológica.
Pruebas de laboratorio: obtenemos análisis de orina en todos los pacientes
evaluados para BPH/LUTS. El propósito es identificar piuria, glucosuria,
proteinuria, cetonuria o bacteriuria, que pueden ser signos de diagnósticos
alternativos y, por lo tanto, justifican una evaluación adicional. Aunque la
hematuria leve puede ocurrir con BPH, el hallazgo de hematuria requiere una
evaluación adicional para otros trastornos genitourinarios como el cáncer de
próstata o de vejiga, especialmente en hombres mayores.
Otros estudios no se realizan de forma rutinaria, pero pueden ser útiles en
determinadas circunstancias:
● No se necesita un cultivo de orina a menos que haya otra evidencia que
sugiera una infección del tracto urinario (ITU; es decir, disuria en el
contexto de piuria o bacteriuria en el análisis de orina).
● La creatinina sérica no es necesaria a menos que haya evidencia que
sugiera insuficiencia renal (es decir, alto residuo posmiccional
[PVR]). Una creatinina sérica alta puede ser el resultado de una
obstrucción de la salida de la vejiga (BOO) o una enfermedad renal
subyacente. Si la concentración de creatinina sérica es alta, está indicada
la ecografía renal para evaluar la presencia de hidronefrosis del tracto
superior.
● La prueba del antígeno prostático específico (PSA, por sus siglas en
inglés) no es necesaria para el diagnóstico, pero se puede usar como
indicador del volumen de la próstata cuando se considera el uso de un
inhibidor de la 5-alfa reductasa (5ARI). Estos medicamentos solo son
útiles en hombres cuya próstata pesa más de 35 gramos, lo que se
correlaciona con un PSA >1,5 ng/dl [ 18,19 ]. Además, se debe medir el
PSA antes de iniciar el tratamiento con 5ARI, ya que dicho tratamiento
puede reducir los niveles de PSA (normalmente en 0,5 ng/dl) e influir en la
detección futura del cáncer de próstata [ 11 ].
Debe evitarse el uso rutinario de la citología de orina en el contexto de STUI y
un análisis de orina normal.
Cuestionarios de síntomas: se deben utilizar cuestionarios validados para
medir la gravedad de los síntomas, la molestia de los síntomas y para
documentar la respuesta a las terapias médicas o quirúrgicas. Los más
utilizados son el Índice de Síntomas de la AUA (AUA-SI) y el Índice
Internacional de Síntomas de la Próstata (IPSS). Uno de estos debe obtenerse
en cada visita [ 20 ]
Medición del volumen residual posterior a la micción : obtenemos una
medición del volumen de PVR en todos los pacientes que presentan síntomas
de STUI/HPB para evaluar la retención según lo recomendado por grupos de
expertos [ 12,21 ]. La PVR se puede medir con la ayuda de un "escáner de
vejiga" junto a la cama, que utiliza ultrasonografía para estimar el volumen de
la vejiga, o mediante el uso de un catéter recto después de la conclusión de
una micción espontánea. La palpación vesical no es un método fiable para
estimar la RVP.
Los STUI de moderados a graves se asocian con una mayor incidencia de
retención urinaria aguda [ 22 ]. Los hombres normales tienen menos de 12 ml
de orina residual, pero la mayoría de los urólogos no se preocupan a menos
que el volumen de PVR sea superior a 250 ml.
Existe una variabilidad interpersonal significativa en las mediciones de PVR, y
su mayor valor está en los cambios a lo largo del tiempo. El aumento de la RVP
puede indicar un fracaso del tratamiento o indicar una intervención
quirúrgica. Una PVR inicial alta indica una mayor probabilidad de deterioro
sintomático con el tiempo [ 18,23 ].
Pruebas adicionales para pacientes seleccionados
Imágenes de la próstata: no se necesita una ecografía transrectal para el
diagnóstico. Sólo está indicado cuando la elección del tratamiento de
STUI/HPB depende del volumen prostático total, como en el uso de 5ARI, o en
la elección de determinadas técnicas quirúrgicas. Es importante recordar que el
tamaño de la glándula prostática no se correlaciona con el grado de
obstrucción ni con la presencia o severidad de STUI.
Se desaconseja el uso rutinario de tomografía computarizada (TC) o
resonancia magnética nuclear (RMN) con el único propósito de STUI/HPB,
aunque la reutilización de imágenes transversales y sagitales medias
realizadas para otras indicaciones puede ser útil cuando la elección de
tratamiento de STUI/HPB depende del volumen prostático total [ 12 ].
Cistoscopia : la cistoscopia o, dicho de manera más correcta, la
uretrocistoscopia no es necesaria en la evaluación de rutina de STUI/HPB
[ 11 ]. Debe considerarse en hombres con antecedentes sugestivos de
estenosis uretral o contractura del cuello de la vejiga. Además, los urólogos
también realizan rutinariamente uretrocistoscopia para ayudar a planificar el
tratamiento quirúrgico de los hombres con HBP.
Pruebas dinámicas: las pruebas urodinámicas adicionales, que suelen
realizar los urólogos, pueden ser complementos útiles en la evaluación de STUI
en algunos pacientes. La uroflujometría es un procedimiento en el consultorio
que puede ayudar a respaldar el diagnóstico de BPH al documentar la
obstrucción; velocidades de flujo de <10 ml/s han mostrado una especificidad
del 70 %, un valor predictivo positivo del 70 % y una sensibilidad del 47 % para
la obstrucción [ 24 ]. Si el estado del paciente no sugiere obstrucción (p. ej.,
flujo urinario máximo [Q máx .] >10 ml/seg), se deben considerar estudios de flujo
de presión (PFS), que son invasivos (que requieren el uso de un catéter
urodinámico de calibre pequeño) pero más concluyentes en cuanto a la causa
de los síntomas. La PFS es útil en tales casos porque las intervenciones
empíricas corren el riesgo de fallar en ausencia de obstrucción. PFS también
se puede utilizar en la evaluación de pacientes cuyas manifestaciones clínicas
son atípicas o cuando hay motivos para sospechar un diagnóstico alternativo
(es decir, vejiga neurogénica por parkinsonismo).
DIAGNÓSTICO
El diagnóstico de síntomas del tracto urinario inferior (STUI)/hiperplasia
prostática benigna (HPB) se establece por la presencia de síntomas urinarios
de acumulación, vaciado y/o irritativos en ausencia de antecedentes, exámenes
o hallazgos de laboratorio que sugieran causas distintas de la HPB. LUTS.
El diagnóstico no requiere confirmación histológica. Una biopsia de próstata
solo está justificada si existe preocupación sobre el cáncer de próstata, como
una glándula asimétrica o nodular en el examen rectal digital (DRE) o un nivel
de antígeno prostático específico (PSA) aumentado o en aumento.
INDICACIONES PARA LA REMISIÓN A UROLOGÍA
La derivación a un especialista en urología puede ser apropiada para pacientes
con cualquiera de los siguientes:
●Síntomas severos o dolor
●Hombres < 45 años
●Anomalía en el tacto rectal
●hematuria
●Antígeno prostático específico (PSA) elevado
●La disuria como posible síntoma de cáncer de vejiga
●Incontinencia
● Enfermedad neurológica conocida por afectar los síntomas del tracto
urinario inferior (STUI)
● Retención urinaria (volumen de orina residual posmiccional [PVR] >250
ml o vejiga palpable)
●Sospecha de otra enfermedad urológica
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Chapter 3: Symptoms of Disorders of the Genitourinary Tract

SYMPTOMS RELATED TO THE ACT OF URINATION

Many conditions cause symptoms of “cystitis.” These include infections of the bladder, vesical inflammation due to chemical or x­radiation reactions,
interstitial cystitis, prostatitis, mental illness (eg, depression and anxiety), torsion or rupture of an ovarian cyst, and foreign bodies in the bladder.
Often, however, the patient with chronic cystitis notices no symptoms of vesical irritability. Irritating chemicals or soap on the urethral meatus may
cause cystitis­like symptoms of dysuria, frequency, and urgency. This has been specifically noted in young girls taking frequent bubble baths.

Frequency

The normal capacity of the bladder is about 400 mL. Frequency may be caused by residual urine, which decreases the functional capacity of the organ.
When the mucosa, submucosa, and even the muscularis become inflamed (eg, infection, foreign body, stones, tumor), the capacity of the bladder
decreases sharply. This decrease is due to two factors: the pain resulting from even mild stretching of the bladder and the loss of bladder compliance
resulting from inflammatory edema. When the bladder is normal, urination can be delayed if circumstances require it, but this is not so in acute cystitis.
Once the diminished bladder capacity is reached, any further distention may be agonizing, and the patient may urinate involuntarily if voiding does not
occur immediately. During very severe acute infections, the desire to urinate may be constant, and each voiding may produce only a few milliliters of
urine. Day frequency without nocturia and acute or chronic frequency lasting only a few hours suggest nervous tension.

Diseases that cause fibrosis of the bladder are accompanied by frequency of urination. Examples of such diseases are tuberculosis, radiation cystitis,
interstitial cystitis, and schistosomiasis. The presence of stones or foreign bodies causes vesical irritability, but secondary infection is almost always
present. A very low or very high urine pH can irritate the bladder and cause frequency of urination. Alcohol, caffeine, carbonated beverages, citrus,
spicy foods, and chocolate can be bladder irritants that cause frequency and pain in some people.

Nocturia

Nocturia may be a symptom of renal disease related to a decrease in the functioning renal parenchyma with loss of concentrating power. Nocturia can
occur in the absence of disease in persons who drink excessive amounts of fluid in the late evening. Coffee and alcoholic beverages, because of their
specific diuretic effects, often produce nocturia if consumed just before bedtime. In older people who are ambulatory, some fluid retention may
develop secondary to mild heart failure or varicose veins. With recumbency at night, this fluid is mobilized, leading to nocturia in these patients.

Dysuria

Painful urination is usually related to acute inflammation of the bladder, urethra, or prostate. At times, the pain is described as “burning” on urination
and is usually located in the distal urethra in men. In women the pain is usually localized to the urethra. The pain is present only with voiding and
disappears soon after micturition is completed. More severe pain sometimes occurs in the bladder just at the end of voiding, suggesting that
inflammation of the bladder is the likely cause. Pain also may be more marked at the beginning of or throughout the act of urination. Dysuria often is
the first symptom suggesting urinary infection and is often associated with urinary frequency and urgency.

Enuresis

Strictly speaking, enuresis means bedwetting at night. It is physiologic during the first 2 or 3 years of life but becomes troublesome, particularly to
parents, after that age. It may be functional or secondary to delayed neuromuscular maturation of the urethrovesical component, but it may present as
a symptom of organic disease (eg, infection, distal urethral stenosis in girls, posterior urethral valves in boys, neurogenic bladder). If wetting occurs
also during the daytime, however, or if there are other urinary symptoms, urologic investigation is essential. In adult life, enuresis may be replaced by
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SYMPTOMS RELATED TO THE ACT OF URINATION, Benjamin N. Breyer Page 1 / 4
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Symptoms of Bladder Outlet Obstruction

A. Hesitancy
Enuresis
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Strictly speaking, enuresis means bedwetting at night. It is physiologic during the first 2 or 3 years of life but becomes
Access troublesome, particularly to
Provided by:

parents, after that age. It may be functional or secondary to delayed neuromuscular maturation of the urethrovesical component, but it may present as
a symptom of organic disease (eg, infection, distal urethral stenosis in girls, posterior urethral valves in boys, neurogenic bladder). If wetting occurs
also during the daytime, however, or if there are other urinary symptoms, urologic investigation is essential. In adult life, enuresis may be replaced by
nocturia for which no organic basis can be found.

Symptoms of Bladder Outlet Obstruction

A. Hesitancy

Hesitancy in initiating the urinary stream is one of the early symptoms of bladder outlet obstruction. As the degree of obstruction increases, hesitancy
is prolonged and the patient often strains to force urine through the obstruction. Prostate obstruction and urethral stricture are common causes of
this symptom.

B. Loss of Force and Decrease of Caliber of the Stream

Progressive loss of force and caliber of the urinary stream is noted as urethral resistance increases despite the generation of increased intravesical
pressure. This can be evaluated by measuring urinary flow rates; in normal circumstances with a full bladder, a maximal flow of 20 mL/s should be
achieved.

C. Terminal Dribbling

Terminal dribbling becomes more and more noticeable as obstruction progresses and is a most distressing symptom.

D. Urgency

A strong, sudden desire to urinate is caused by hyperactivity and irritability of the bladder, resulting from obstruction, inflammation, or neuropathic
bladder disease. In most circumstances, the patient can control the sudden need to void temporarily, but loss of small amounts of urine may occur
(urgency incontinence).

E. Acute Urinary Retention

Sudden inability to urinate may supervene. The patient experiences increasingly agonizing suprapubic pain associated with severe urgency and may
dribble only small amounts of urine.

F. Chronic Urinary Retention

Chronic urinary retention may cause little discomfort to the patient even though there is great hesitancy in starting the stream and marked reduction of
its force and caliber. Constant dribbling of urine (overflow incontinence) may be experienced; it may be likened to water pouring over a dam.

G. Intermittent Urinary Stream

Interruption may be abrupt and accompanied by severe pain radiating down the urethra. This type of reaction strongly suggests the complication of
vesical calculus or prostate growth resembling a ball and valve.

H. Sense of Incomplete Emptying

The patient often feels that urine is still in the bladder even after urination has been completed.

I. Cystitis

Recurring episodes of acute cystitis suggest the presence of residual urine.

Incontinence

There are many reasons for incontinence. The history often gives a clue to its cause. (See also Chapter 29.)

A. True Incontinence
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symptom. The more obvious causes include previous radical
prostatectomy, exstrophy of the bladder, epispadias, vesicovaginal fistula, and ectopic ureteral orifice. Injury to the urethral smooth­muscle sphincters
may occur during prostatectomy or childbirth. Congenital or acquired neurogenic diseases may lead to dysfunction of the bladder and incontinence.
Recurring episodes of acute cystitis suggest the presence of residual urine.
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Incontinence Access Provided by:

There are many reasons for incontinence. The history often gives a clue to its cause. (See also Chapter 29.)

A. True Incontinence

The patient may lose urine without warning; this may be a constant or periodic symptom. The more obvious causes include previous radical
prostatectomy, exstrophy of the bladder, epispadias, vesicovaginal fistula, and ectopic ureteral orifice. Injury to the urethral smooth­muscle sphincters
may occur during prostatectomy or childbirth. Congenital or acquired neurogenic diseases may lead to dysfunction of the bladder and incontinence.

B. Stress Incontinence

When slight weakness of the sphincteric mechanisms is present, urine may be lost in association with physical strain (eg, coughing, laughing, rising
from a chair). This is common in multiparous women who have weakened muscle support of the bladder neck and urethra and in men who have
undergone radical prostatectomy. Occasionally, neuropathic bladder dysfunction can cause stress incontinence. The patient stays dry while lying in
bed.

C. Urge Incontinence

Urgency may be so precipitate and severe that there is involuntary loss of urine. Urge incontinence frequently occurs with acute cystitis, particularly in
women, since women seem to have relatively poor anatomic sphincters. Urge incontinence is a common symptom of an upper motor neuron lesion.

D. Overflow Incontinence

Paradoxic incontinence is loss of urine due to chronic urinary retention or secondary to a flaccid bladder. The intravesical pressure finally equals the
urethral resistance; urine then constantly dribbles forth.

Oliguria and Anuria

Oliguria and anuria may be caused by acute renal failure (due to shock or dehydration), fluid ion imbalance, or bilateral ureteral obstruction.

Pneumaturia

The passage of gas in the urine strongly suggests a fistula between the urinary tract and the bowel. This occurs most commonly in the bladder or
urethra but may be seen also in the ureter or renal pelvis. Carcinoma of the sigmoid colon, diverticulitis with abscess formation, regional enteritis, and
trauma cause most vesical fistulas. Congenital anomalies account for most urethroenteric fistulas. Certain bacteria, by the process of fermentation,
may liberate gas on rare occasions independent of a fistula.

Cloudy Urine

Patients often complain of cloudy urine, but it is most often cloudy merely because it is alkaline; this causes precipitation of phosphate. Infection can
also cause urine to be cloudy and malodorous. A properly performed urinalysis will reveal the cause of cloudiness.

Chyluria

The passage of lymphatic fluid or chyle is noted by the patient as passage of milky white urine. This represents a lymphatic–urinary system fistula. Most
often, the cause is obstruction of the renal lymphatics, which results in forniceal rupture and leakage. Filariasis, trauma, tuberculosis, and
retroperitoneal tumors have caused this problem.

Bloody Urine

Hematuria is a danger signal that cannot be ignored. Carcinoma of the kidney or bladder, calculi, and infection are a few of the conditions in which
hematuria is typically demonstrable at the time of presentation. It is important to know whether urination is painful, whether the hematuria is
associated with symptoms of vesical irritability, and whether blood is seen in all or only a portion of the urinary stream. The hemoglobinuria that
occurs as a feature of the hemolytic syndromes may also cause the urine to be red.

A. Bloody Urine in Relation to Symptoms and Diseases

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SYMPTOMS associated
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THEcolic
ACTsuggests a ureteral Benjamin
OF URINATION, stone, although a clot from a bleeding renal tumor can cause the same type of pain.Page 3 / 4
N. Breyer
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Hematuria is commonly associated with nonspecific, tuberculous, or schistosomal infection of the bladder. The bleeding is often terminal (bladder
neck or prostate), although it may be present throughout urination (vesical or upper tract). Stone in the bladder often causes hematuria, but infection
hematuria is typically demonstrable at the time of presentation. It is important to know whether urination is painful, whether the hematuria is
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associated with symptoms of vesical irritability, and whether blood is seen in all or only a portion of the urinary stream. The hemoglobinuria that
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occurs as a feature of the hemolytic syndromes may also cause the urine to be red.

A. Bloody Urine in Relation to Symptoms and Diseases

Hematuria associated with renal colic suggests a ureteral stone, although a clot from a bleeding renal tumor can cause the same type of pain.

Hematuria is commonly associated with nonspecific, tuberculous, or schistosomal infection of the bladder. The bleeding is often terminal (bladder
neck or prostate), although it may be present throughout urination (vesical or upper tract). Stone in the bladder often causes hematuria, but infection
is usually present, and there are symptoms of bladder neck obstruction, neurogenic bladder, or cystocele.

Dilated veins may develop at the bladder neck secondary to enlargement of the prostate. These may rupture when the patient strains to urinate,
resulting in gross or microscopic hematuria.

Hematuria without other symptoms (silent hematuria) must be regarded as a symptom of tumor of the bladder or kidney until proved otherwise. It is
usually intermittent; bleeding may not recur for months. Because the bleeding stops spontaneously, complacency must be condemned. Less common
causes of silent hematuria are staghorn calculus, polycystic kidneys, benign prostatic hyperplasia, solitary renal cyst, sickle cell disease, and
hydronephrosis. Painless bleeding is common with acute glomerulonephritis. Recurrent bleeding is occasionally seen in children suffering from focal
glomerulitis. Joggers and people who engage in contact sports frequently develop transient proteinuria and gross or microscopic hematuria.

B. Time of Hematuria

Learning whether the hematuria is partial (initial, terminal) or total (present throughout urination) is often of help in identifying the site of bleeding.
Initial hematuria suggests an anterior urethral lesion (eg, urethritis, stricture, meatal stenosis in young boys). Terminal hematuria usually arises from
the posterior urethra, bladder neck, or trigone. Among the common causes are posterior urethritis and polyps and tumors of the vesical neck. Total
hematuria has its source at or above the level of the bladder (eg, stone, tumor, tuberculosis, nephritis).

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Smith & Tanagho's General Urology, 19e

Chapter 3: Symptoms of Disorders of the Genitourinary Tract

OTHER OBJECTIVE MANIFESTATIONS

Urethral Discharge

Urethral discharge in men is one of the most common urologic complaints. The causative organism is usually Neisseria gonorrhoeae or Chlamydia
trachomatis. The discharge is often accompanied by local burning on urination or an itching sensation in the urethra (see Chapter 17).

Skin Lesions of the External Genitalia

An ulceration of the glans penis or its shaft may represent syphilitic chancre, chancroid, herpes simplex, or squamous cell carcinoma. Venereal warts of
the penis are common. (See Chapters 17 and 42.)

Visible or Palpable Masses

The patient may notice a visible or palpable mass in the upper abdomen that may represent a renal tumor, hydronephrosis, or polycystic kidney.
Enlarged lymph nodes in the neck may contain metastatic tumor from the prostate or testis. Lumps in the groin may represent spread of tumor of the
penis or lymphadenitis from chancroid, syphilis, or lymphogranuloma venereum. Painless masses in the scrotal contents are common and include
hydrocele, varicocele, spermatocele, chronic epididymitis, hernia, and testicular tumor.

Edema

Edema of the legs may result from compression of the iliac veins by lymphatic metastases from prostatic cancer. Edema of the genitalia suggests
filariasis, chronic ascites, or lymphatic blockage from radiotherapy for pelvic malignancies.

Bloody Ejaculation

Inflammation of the prostate or seminal vesicles can cause hematospermia.

Gynecomastia

Often idiopathic, gynecomastia is common in elderly men, particularly those taking estrogens for control of prostatic cancer. It is also seen in
association with choriocarcinoma and interstitial cell and Sertoli cell tumors of the testis. Certain endocrinologic diseases, such as Klinefelter
syndrome, may also cause gynecomastia.

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 CURSO PM ENDOCRINO REPRODUCTOR EXCRETOR
PRÁCTICA DE SIMULACIÓN
SEMANA 2

LOGRO DEL APRENDIZAJE

Al finalizar la sesión, el estudiante aplica las técnicas de evaluación del sistema genitourinario del varón

HABILIDAD 1
1. El docente demuestra la técnica de evaluación de los genitales masculinos
2. Los estudiantes realizan el examen físico de los genitales masculinos
3. El docente verifica con la lista de chequeo la técnica de evaluación de genitales masculinos y realiza retroalimentación

LISTA DE CHEQUEO: EXAMEN DE GENITALES MASCULINOS

PASOS ACTIVIDAD REALIZÓ NO REALIZÓ COMENTARIO

Saluda al paciente, le informa y solicita consentimiento
1 sobre el procedimiento a realizar
2 Lavado de manos antes del procedimiento.
Le pide al paciente que se coloque en decúbito dorsal o de
3 pie
4 Se coloca los guantes.
INSPECCIÓN Y PALPACIÓN
Pubis: Observa la distribución del vello, busca lesiones y
5 decoloración de la piel y/o mucosas
Pene
6 Observa, busca lesiones.
Evidencia si está o no circuncidado, si no lo está retrae el
7 prepucio, observa la ausencia de esmegma.
8 Evalúa el meato uretral y busca lesiones o secreciones.
9 Palpa el cuerpo del pene y lo ordeña
Escroto
10 Busca lesiones
Palpa los testículos uno por uno (Tamaño, consistencia,
11 sensibilidad, lesiones)
12 Palpa epidídimo
En caso de dolor busca el signo de Prehn: elevación del
testículo hacia su canal inguinal buscando alivio
13 (epididimitis)
Otros
14 Busca reflejo cremastérico
Busca hernias inguinales en bipedestación. Inspección.
Palpación: evaluador coloca índice derecho en lado derecho
del escroto, lo dirige hacia anillo inguinal superficial y solicita
15 maniobra de Valsalva al paciente.
16 Palpación de ganglios linfáticos inguinales
17 Lavado de manos después del procedimiento.

HABILIDAD 2
1. El docente demuestra la técnica de evaluación de la próstat a través del tacto rectal
2. Los estudiantes realizan el examen de próstata través del tacto rectal
3. El docente verifica con la lista de chequeo el examen de la próstata a través del tacto rectal y realiza retroalimentación

LISTA DE CHEQUEO: TACTO RECTAL

PASOS ACTIVIDAD REALIZÓ NO REALIZÓ COMENTARIO

Saluda al paciente, le informa y solicita consentimiento
1 sobre el procedimiento a realizar
2 Lavado de manos antes del procedimiento.
3 Se coloca los guantes
Coloca al paciente en decúbito lateral izquierdo con las
caderas y las rodillas flexionadas o de pie con las caderas
flexionadas y el tronco en la camilla o en la posición de Sims
4
5 Inspecciona las áreas sacrococcigea y perianal
Separa las nalgas del paciente con las 2 manos e
inspecciona el ano, evalúa la piel y pide que haga fuerza
6
 Lubrica el dedo índice (con la palma de la mano hacia
abajo), lo coloca sobre el orificio anal y hace una leve
7 presión para que el esfínter se relaje
Pide al paciente que haga una respiración profunda (para
relajar el esfínter externo), introduce la punta del dedo en el
8 canal anal y evalúa el tono del esfínter
Introduce el dedo y palpa en forma secuencial las paredes
laterales y posterior en busca de cualquier nódulo, masa,
9 irregularidad , pólipo o de dolor.
Gira el dedo índice para palpar la pared rectal anterior y
palpa la superficie posterior de la glándula prostática en la
que se evalúa: tamaño,forma, superficie, consistencia ,
10 sensibilidad y busca alguna lesión nodular o tumoral.
Retira el dedo con suavidad, observa su dedo de guante
para evaluar secreciones y comunica al paciente que ha
11 finalizado el examen.
12 Se retira los guantes y se lava las manos
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Current Medical Diagnosis & Treatment 2025

28­08: Hypothyroidism & Myxedema

Paul A. Fitzgerald

ESSENTIALS OF DIAGNOSIS

ESSENTIALS OF DIAGNOSIS

Hashimoto autoimmune thyroiditis is the most common cause of hypothyroidism.

Fatigue, cold intolerance, constipation, weight change, depression, menorrhagia, hoarseness.

Dry skin, bradycardia, delayed return of deep tendon reflexes.

FT4 is usually low.

TSH elevated in primary hypothyroidism.

GENERAL CONSIDERATIONS
Hypothyroidism is common, with 0.3% of the population having overt disease. About 85% of affected individuals are women. Thyroid hormone
deficiency affects almost all body functions. The degree of severity ranges from mild and unrecognized hypothyroid states to striking myxedema. The
fluid retention seen in myxedema is caused by the interstitial accumulation of hydrophilic mucopolysaccharides, which leads to lymphedema.
Hyponatremia is the result of impaired renal tubular sodium reabsorption due to reductions in Na+–K+­ATPase. Maternal hypothyroidism during
pregnancy results in offspring with IQ scores that are an average 7 points lower than those of euthyroid mothers. Congenital hypothyroidism occurs in
about 1:4000 births; untreated, it causes cretinism with permanent cognitive impairment.

Hypothyroidism may be due to failure or resection of the thyroid gland itself (primary hypothyroidism) or deficiency of pituitary TSH (secondary
hypothyroidism; see Hypopituitarism). Autoimmune thyroiditis is the most common cause of hypothyroidism (see Thyroiditis). A hypothyroid phase
also occurs in subacute (de Quervain) viral thyroiditis following initial hyperthyroidism.

Goiter (thyroid enlargement) may be present with thyroiditis, iodide deficiency, genetic thyroid enzyme defects, food goitrogens in iodide­deficient
areas (eg, turnips, cassavas), or, rarely, peripheral resistance to thyroid hormone or infiltrating diseases (eg, cancer, sarcoidosis). Goitrogenic
medications include iodide, propylthiouracil (PTU) or methimazole, sulfonamides, amiodarone, interferon­alpha, interferon­beta, interleukin­2, and
lithium. About 50% of patients taking lithium long term have an ultrasound­detectable goiter. Goiter is often absent in patients with autoimmune
thyroiditis or hypothyroidism due to destruction of the gland by head­neck or chest­shoulder radiation therapy or 131I therapy. Total thyroidectomy
causes hypothyroidism; after hemithyroidectomy, hypothyroidism develops in 22% of patients.

Amiodarone, because of its high iodine content, causes clinically significant hypothyroidism in 15–20% of patients as well as thyrotoxicosis (see
Amiodarone­induced thyrotoxicosis, below). Hypothyroidism occurs most often in patients with preexisting autoimmune thyroiditis. The T4 level is low
or low­normal, and the TSH is elevated, usually over 20 mIU/L. Another 17% of patients taking amiodarone are asymptomatic with normal serum T4
levels despite elevations in serum TSH; they can be closely monitored without levothyroxine therapy. Low­dose amiodarone is less likely to cause
hypothyroidism. Patients with CAD who have amiodarone­induced symptomatic hypothyroidism are treated with just enough levothyroxine to relieve
symptoms. Hypothyroidism usually resolves over several months if amiodarone is discontinued.

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develop IP is with a high iodine intake, especially if they have underlying lymphocytic thyroiditis. Some malignancies
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28­08: Hypothyroidism &amp; Myxedema, Paul A.(type
overexpress thyroid hormone inactivating enzyme Fitzgerald
3 deiodinase) and cause “consumptive hypothyroidism.” This has occurred with large
Page 1 / 10
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hemangiomas or a heavy tumor burden of colon cancer, basal cell cancer, fibrous tumors, or gastrointestinal stromal tumors (GISTs).

Chemotherapeutic agents that can cause silent thyroiditis include tyrosine kinase inhibitors, denileukin diftitox, alemtuzumab, interferon­alpha,
or low­normal, and the TSH is elevated, usually over 20 mIU/L. Another 17% of patients taking amiodarone are asymptomatic
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denormal serum
Ciencias T4
Aplicadas
levels despite elevations in serum TSH; they can be closely monitored without levothyroxine therapy. Low­dose amiodarone
Access Provided by: is less likely to cause
hypothyroidism. Patients with CAD who have amiodarone­induced symptomatic hypothyroidism are treated with just enough levothyroxine to relieve
symptoms. Hypothyroidism usually resolves over several months if amiodarone is discontinued.

Hypothyroidism may also develop in patients with a high iodine intake, especially if they have underlying lymphocytic thyroiditis. Some malignancies
overexpress thyroid hormone inactivating enzyme (type 3 deiodinase) and cause “consumptive hypothyroidism.” This has occurred with large
hemangiomas or a heavy tumor burden of colon cancer, basal cell cancer, fibrous tumors, or gastrointestinal stromal tumors (GISTs).

Chemotherapeutic agents that can cause silent thyroiditis include tyrosine kinase inhibitors, denileukin diftitox, alemtuzumab, interferon­alpha,
interleukin­2, thalidomide, lenalidomide, and immune checkpoint inhibitors (pembrolizumab, ipilimumab, tremelimumab, and atezolizumab).
Thyroiditis usually starts with hyperthyroidism (often unrecognized) and then progresses to hypothyroidism. RAI­based targeted radioisotope therapy
can also cause hypothyroidism. Mifepristone causes primary hypothyroidism and an increased dose requirement for thyroid hormone replacement.
Mitotane causes secondary hypothyroidism.

CLINICAL FINDINGS
A. Symptoms and Signs

1. Common manifestations

Mild hypothyroidism often escapes detection. Patients typically have nonspecific symptoms that include weight gain, fatigue, lethargy, depression,
weakness, dyspnea on exertion, arthralgias or myalgias, muscle cramps, menorrhagia, constipation, dry skin, headache, paresthesias, cold
intolerance, carpal tunnel syndrome, and Raynaud syndrome. Physical findings can include bradycardia; diastolic hypertension; thin, brittle nails;
thinning of hair; peripheral edema; puffy face and eyelids (eFigure 28–4); and skin pallor or yellowing (carotenemia). Delayed relaxation of deep
tendon reflexes may be present. Patients often have a goiter that arises due to elevated serum TSH levels or the underlying thyroid pathology.

eFigure 28–4.

Hypothyroidism in adult (myxedema). Note puffy face, puffy eyes, frowzy hair, and dull and apathetic appearance. (Reproduced, with permission, from
Greenspan FS, Strewler GJ [editors]. Basic & Clinical Endocrinology, 5th ed. Copyright © 1997 by The McGraw­Hill Companies, Inc.)

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©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
eFigure 28–4.
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Hypothyroidism in adult (myxedema). Note puffy face, puffy eyes, frowzy hair, and dull and apathetic appearance. (Reproduced, with permission, from
Greenspan FS, Strewler GJ [editors]. Basic & Clinical Endocrinology, 5th ed. Copyright © 1997 by The McGraw­Hill Companies, Inc.)

2. Less common manifestations

Less common symptoms of hypothyroidism include diminished appetite and weight loss, hoarseness, decreased sense of taste and smell, and
diminished auditory acuity. Some patients with goiter may report dysphagia or neck discomfort. Although most menstruating women have
menorrhagia, some women have scant menses or amenorrhea. Physical findings may include loss of eyelash and eyebrow hairs; thickening of the
tongue; hard pitting edema; and effusions into the pleural and peritoneal cavities as well as into joints. Galactorrhea may also be present. Cardiac
enlargement (“myxedema heart”) and pericardial effusions may develop. Psychosis “myxedema madness” can occur from severe hypothyroidism or
from toxicity of other drugs whose metabolism is slowed in hypothyroidism.

Some hypothyroid patients with autoimmune thyroiditis have symptoms that are not due to hypothyroidism but rather to conditions associated with
autoimmune thyroiditis; these include Addison disease, hypoparathyroidism, diabetes mellitus, pernicious anemia, Sjögren syndrome, vitiligo, biliary
cirrhosis, gluten sensitivity, and celiac disease.

Celiac disease occurs in at least 5% of patients with hypothyroidism due to autoimmune thyroiditis. Affected patients often have GI symptoms, fatigue,
headaches, cognitive difficulties, depression, paresthesias, weight loss, osteoporosis or osteomalacia, or anemia. Women may have amenorrhea,
infertility, or recurrent miscarriage. Intestinal malabsorption may cause vitamin deficiencies.

B. Laboratory Findings

Hypothyroidism is a common disorder and thyroid function tests should be obtained for any patient with its nonspecific symptoms or signs. The single
best screening test for hypothyroidism is the serum TSH (Table 28–2). In primary hypothyroidism, the serum TSH is increased in a reflex effort to
stimulate the failing gland, while the serum FT4 is low or low­normal. The normal reference range for ultrasensitive TSH levels is generally 0.4–4.0
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28­08: Hypothyroidism
mIU/L. Over 95% of normal &amp; Myxedema,
adults Paul
have serum TSHA.concentrations
Fitzgerald under 3.0 mIU/L. However, there is considerable controversy about whatPagerepresents
3 / 10
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
“normal,” such that each laboratory uses a slightly different range. The normal range of TSH varies with age; for example, the reference range for both
children and older patients is higher than the reference range for younger patients.
 Universidad Peruana de Ciencias Aplicadas
B. Laboratory Findings
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Hypothyroidism is a common disorder and thyroid function tests should be obtained for any patient with its nonspecific symptoms or signs. The single
best screening test for hypothyroidism is the serum TSH (Table 28–2). In primary hypothyroidism, the serum TSH is increased in a reflex effort to
stimulate the failing gland, while the serum FT4 is low or low­normal. The normal reference range for ultrasensitive TSH levels is generally 0.4–4.0
mIU/L. Over 95% of normal adults have serum TSH concentrations under 3.0 mIU/L. However, there is considerable controversy about what represents
“normal,” such that each laboratory uses a slightly different range. The normal range of TSH varies with age; for example, the reference range for both
children and older patients is higher than the reference range for younger patients.

Table 28–2.
Appropriate use of thyroid tests.

Test Comment

For screening Serum TSH Most sensitive test for primary hypo­ and hyperthyroidism
Free thyroxine (FT4) Excellent test

For Serum TSH High in primary and low in secondary hypothyroidism

hypothyroidism Thyroid peroxidase and Elevated in autoimmune (Hashimoto) thyroiditis
thyroglobulin
antibodies

For Serum TSH Suppressed except in TSH­secreting pituitary tumor or pituitary hyperplasia (rare)
hyperthyroidism Triiodothyronine (T3) or Elevated

free triiodothyronine Increased uptake; diffuse versus “hot” foci on scan

(FT3) Elevated in Graves disease

123I uptake and scan

Usually (65%) positive in Graves disease

Thyroid peroxidase and

thyroglobulin
antibodies
Thyroid­stimulating
immunoglobulin (TSI)

For thyroid Fine­needle aspiration Best diagnostic method for thyroid cancer
nodules (FNA) biopsy Cancer is usually “cold”; less reliable than FNA biopsy
123I uptake and scan Vascular versus less vascular
99mTc scan Useful to assist FNA biopsy. Useful in assessing the risk of malignancy (multinodular goiter or pure cysts
are less likely to be malignant). Useful to monitor nodules and patients after thyroid surgery for
Ultrasonography
carcinoma.

Other laboratory abnormalities can include hypoglycemia or anemia (with normal or increased mean corpuscular volume). Hyponatremia due to the
syndrome of inappropriate ADH secretion (SIADH) or decreased GFR is common. Additional frequent findings include increased serum levels of LDL
cholesterol, triglycerides, lipoprotein(a), liver enzymes, creatine kinase, or PRL. Semen analysis shows an increase in abnormal sperm morphology. In
patients with autoimmune thyroiditis, titers of antibodies against TPO and TG are high; serum ANA may be present but are rarely indicative of lupus.

Subclinical hypothyroidism is defined as the state of having a normal serum FT4 with a serum TSH that is above the reference range. It occurs most
often in persons aged 65 years or older, in whom the prevalence is 13%. Subclinical hypothyroidism is often transient, and serum TSH levels normalize
spontaneously in about 60% of cases within 5 years. The likelihood of TSH normalization is higher in patients without antithyroid antibodies and those
with a marginally elevated serum TSH. The term “subclinical” is somewhat misleading, since it refers to the serum hormone levels and not the patient’s
symptoms.

C. Imaging
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is usually P necessary
not Your IP isfor patients with hypothyroidism. On CT or MRI, a goiter may be noted in the neck or in the mediastinum
28­08: Hypothyroidism &amp; Myxedema, Paul A. Fitzgerald Page 4 / 10
(retrosternal
©2025 McGraw goiter).
Hill. An
All enlarged thymus is frequently
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Terms of Use cases of
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hypothyroidism, due to hyperplasia of TSH­secreting cells.
spontaneously in about 60% of cases within 5 years. The likelihood of TSH normalization is higher in patients without antithyroid antibodies and those
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patient’s
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C. Imaging

Radiologic imaging is usually not necessary for patients with hypothyroidism. On CT or MRI, a goiter may be noted in the neck or in the mediastinum
(retrosternal goiter). An enlarged thymus is frequently seen in cases of autoimmune thyroiditis. On MRI, the pituitary is often quite enlarged in primary
hypothyroidism, due to hyperplasia of TSH­secreting cells.

DIFFERENTIAL DIAGNOSIS
The differential diagnosis for subclinical hypothyroidism (low serum T4 or high serum TSH in the absence of hypothyroidism) includes antibody
interference with the serum TSH assay, macro­TSH, sleep deprivation, exercise, recovery from nonthyroidal illness, acute psychiatric emergencies, and
other conditions and medications (Table 28–3).

Table 28–3.

Factors that may cause aberrations in laboratory tests that may be mistaken for primary hypothyroidism.1

Low Serum T4 o r T3 High Serum TSH

Acute psychiatric illness Acute psychiatric illness (transient) (14%)

Cirrhosis Amiodarone
Familial thyroid­binding globulin deficiency Anti­mouse antibodies
Laboratory error Antithyrotropin antibodies
Nephrotic syndrome Anti­TSH receptor antibodies
Severe illness Autoimmune disease (assay interference)
Drugs Drugs
Androgens Allopurinol
Antiseizure drugs Amphetamines
Carbamazepine Atypical antipsychotics
Phenobarbital Dopamine agonists
Phenytoin Heroin
Asparaginase Phenothiazines
Carbamazepine (T4) Exercise before testing

Chloral hydrate Following prolonged primary hypothyroidism

Corticosteroids Heterophile antibodies

Diclofenac (T3), naproxen (T3) Laboratory error

Macro­thyrotropin
Didanosine
Nonadherence to thyroid replacement therapy
Fenclofenac
Older adults (especially women)
5­Fluorouracil
Pituitary TSH hypersecretion
Halofenate
Recovery from acute nonthyroidal illness (transient)
Imatinib
Strenuous exercise (acute)
Mitotane
Sleep deprivation (acute)
Nicotinic acid
TSH resistance
Oxcarbazepine
Phenobarbital
Phenytoin
Salicylates in large doses (T3 and T4)

Sertraline
Stavudine
T 3 therapy (T4)

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triiodothyronine.

Euthyroid sick syndrome should be considered in patients without known thyroid disease who are found to have a low serum FT4 with a serum TSH
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The differential diagnosis for subclinical hypothyroidism (low serum T4 or high serum TSH in the absence of hypothyroidism) includes antibody
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interference with the serum TSH assay, macro­TSH, sleep deprivation, exercise, recovery from nonthyroidal illness, acute psychiatric emergencies, and
other conditions and medications (Table 28–3).

Table 28–3.

Factors that may cause aberrations in laboratory tests that may be mistaken for primary hypothyroidism.1

Low Serum T4 o r T3 High Serum TSH

Acute psychiatric illness Acute psychiatric illness (transient) (14%)

Cirrhosis Amiodarone
Familial thyroid­binding globulin deficiency Anti­mouse antibodies
Laboratory error Antithyrotropin antibodies
Nephrotic syndrome Anti­TSH receptor antibodies
Severe illness Autoimmune disease (assay interference)
Drugs Drugs
Androgens Allopurinol
Antiseizure drugs Amphetamines
Carbamazepine Atypical antipsychotics
Phenobarbital Dopamine agonists
Phenytoin Heroin
Asparaginase Phenothiazines
Carbamazepine (T4) Exercise before testing

Chloral hydrate Following prolonged primary hypothyroidism

Corticosteroids Heterophile antibodies

Diclofenac (T3), naproxen (T3) Laboratory error

Macro­thyrotropin
Didanosine
Nonadherence to thyroid replacement therapy
Fenclofenac
Older adults (especially women)
5­Fluorouracil
Pituitary TSH hypersecretion
Halofenate
Recovery from acute nonthyroidal illness (transient)
Imatinib
Strenuous exercise (acute)
Mitotane
Sleep deprivation (acute)
Nicotinic acid
TSH resistance
Oxcarbazepine
Phenobarbital
Phenytoin
Salicylates in large doses (T3 and T4)

Sertraline
Stavudine
T 3 therapy (T4)

1True primary hypothyroidism may coexist.

T 4, levothyroxine; T3, triiodothyronine.

Euthyroid sick syndrome should be considered in patients without known thyroid disease who are found to have a low serum FT4 with a serum TSH
that is not elevated. This syndrome can be seen in patients with severe illness, caloric deprivation, or major surgery. Patients who have undergone
major surgery may have accelerated peripheral metabolism of serum T4 to reverse T3 (rT3). Furthermore, in most patients who are critically ill, there is
a circulating inhibitor of thyroid hormone binding to serum thyroxine­binding proteins. This causes the RT3U to be misleadingly low, causing the
computed FT4I to be very low. The presence of a very low serum T4 in severe nonthyroidal illness indicates a poor prognosis. Treatment with
levothyroxine is not indicated for patients with euthyroid sick syndrome.
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presence of a goiter suggests the diagnosis. The clinician must decide whether such severely ill patients (with a low serum T4 and low TSH) might have
hypothyroidism due to hypopituitarism. Patients without symptoms of prior brain lesion or hypopituitarism are very unlikely to suddenly develop
that is not elevated. This syndrome can be seen in patients with severe illness, caloric deprivation, or major surgery. Patients who have undergone
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major surgery may have accelerated peripheral metabolism of serum T4 to reverse T3 (rT3). Furthermore, in most patients who are critically ill, there is
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a circulating inhibitor of thyroid hormone binding to serum thyroxine­binding proteins. This causes the RT3U to be misleadingly low, causing the
computed FT4I to be very low. The presence of a very low serum T4 in severe nonthyroidal illness indicates a poor prognosis. Treatment with
levothyroxine is not indicated for patients with euthyroid sick syndrome.

Serum TSH tends to be suppressed in severe nonthyroidal illness, making the diagnosis of concurrent primary hypothyroidism difficult, although the
presence of a goiter suggests the diagnosis. The clinician must decide whether such severely ill patients (with a low serum T4 and low TSH) might have
hypothyroidism due to hypopituitarism. Patients without symptoms of prior brain lesion or hypopituitarism are very unlikely to suddenly develop
hypopituitarism during an unrelated illness. Patients with diabetes insipidus, hypopituitarism, or other signs of a CNS lesion may be given T4
empirically.

Patients receiving prolonged dopamine infusions can develop true secondary hypothyroidism caused by dopamine's direct suppression of TSH­
secreting cells. Bexarotene and mitotane also cause secondary hypothyroidism in most patients.

COMPLICATIONS
Severe or long­standing hypothyroidism may increase susceptibility to bacterial pneumonia or rarely cause megacolon or infertility. Organic
psychoses with paranoid delusions may occur (“myxedema madness”). Rhabdomyolysis may occur and cause kidney dysfunction. Untreated
hypothyroidism during pregnancy often results in miscarriage. Sellar enlargement and even TSH­secreting tumors may develop in untreated cases.
These tumors decrease in size after replacement therapy is instituted. Thyroid therapy may exacerbate preexistent CAD or HF and rarely may
precipitate adrenal crisis.

Myxedema crisis refers to severe symptoms of hypothyroidism that become a threat to life. Of patients with myxedema crisis, 94% have primary
hypothyroidism, 50% have previously undiagnosed hypothyroidism, and 80% are women. Myxedema crisis can also result from failure to take
prescription levothyroxine. It can occur spontaneously in severely hypothyroid patients with prolonged exposure to the cold, with resultant
hypothermia. It also can also be induced by a stroke, HF, infection (particularly pneumonia), or trauma. Myxedema crisis is often precipitated by the
administration of sedatives, antidepressants, hypnotics, anesthetics, or opioids, the metabolism of which is slowed in hypothyroidism. These drugs
further impair cognition and respiratory drive and can precipitate respiratory arrest. All patients with myxedema crisis have some degree of
obtundation, ranging from somnolence to coma. The term “myxedema coma” is a misnomer, since the alertness of affected patients varies from
simple lethargy to coma. Convulsions and abnormal CNS signs may occur. Patients may also present with hyponatremia (65%), hypothermia (50%),
hypotension (40%), bradycardia (20%), hypoglycemia (15%), rhabdomyolysis, and AKI. The mortality rate is high.

TREATMENT
Before beginning therapy with thyroid hormone, the hypothyroid patient requires a clinical assessment for adrenal insufficiency and angina. The
presence of either condition requires further evaluation and management.

For patients with subclinical hypothyroidism, levothyroxine therapy is given to women attempting pregnancy, young adult patients aged 30 years or
younger, patients with serum TSH levels 20 mIU/L or higher, and those with significant symptoms attributable to hypothyroidism. Other patients with
subclinical hypothyroidism do not require levothyroxine therapy but must be monitored regularly for the emergence of symptoms.

A. Treatment of Hypothyroidism

Synthetic levothyroxine is the preferred preparation for treating hypothyroidism. Generic levothyroxine preparations have met FDA criteria for
bioequivalence. However, some patients strongly prefer certain brands. Most generic and brand levothyroxine preparations are tablets, although
capsules and a liquid preparation (Tirosint) are available. Lyophilized preparations of levothyroxine are available for reconstitution and intravenous
administration, when indicated.

Desiccated natural porcine thyroid preparations containing both T4 and T3 (eg, Armour Thyroid, Nature­Throid, NP Thyroid) are prescribed by some
clinicians. About 65 mg (1 grain) of desiccated thyroid is equivalent to 100 mcg of levothyroxine. Several professional societies discourage the use of
desiccated thyroid preparations but many patients prefer them. A possible explanation is that a common genetic variant in deiodinase type 2 gene
(deiodinase type 2 converts T4 to active T3) is associated with worse quality of life scores in hypothyroid patients taking levothyroxine and a better
response to therapy with thyroid preparations containing a mixture of T4 and T3.

Otherwise healthy
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2025­1­25 and middle­aged adults with hypothyroidism may be treated initially with levothyroxine in average doses of about 1.6
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mcg/kg/day. Lower doses can be used for very A.hypothyroidism,
mild Fitzgerald while full doses are given for more symptomatic hypothyroidism. The Page
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hormonal goal of levothyroxine replacement therapy should be to normalize serum TSH levels. Bedtime levothyroxine administration results in
somewhat higher serum T4 and lower TSH levels than morning administration. Therefore, the administration timing for levothyroxine should be kept
clinicians. About 65 mg (1 grain) of desiccated thyroid is equivalent to 100 mcg of levothyroxine. Several professional societies discourage the use of
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desiccated thyroid preparations but many patients prefer them. A possible explanation is that a common genetic variant in deiodinase type 2 gene
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(deiodinase type 2 converts T4 to active T3) is associated with worse quality of life scores in hypothyroid patients taking levothyroxine and a better
response to therapy with thyroid preparations containing a mixture of T4 and T3.

Otherwise healthy young and middle­aged adults with hypothyroidism may be treated initially with levothyroxine in average doses of about 1.6
mcg/kg/day. Lower doses can be used for very mild hypothyroidism, while full doses are given for more symptomatic hypothyroidism. The initial
hormonal goal of levothyroxine replacement therapy should be to normalize serum TSH levels. Bedtime levothyroxine administration results in
somewhat higher serum T4 and lower TSH levels than morning administration. Therefore, the administration timing for levothyroxine should be kept
constant. After beginning daily administration, significant increases in serum T4 levels are seen within 1–2 weeks and near­peak levels within 3–4
weeks.

Pregnant women with overt hypothyroidism or myxedema should be treated immediately with levothyroxine at full replacement doses.

Patients with stable CAD or those who are over age 60 years are treated with smaller initial doses of levothyroxine, 25–50 mcg orally daily; higher
initial doses may be used if such patients are severely hypothyroid. The dose can be increased by 25 mcg every 1–3 weeks until the patient is euthyroid.
Ideally, patients with hypothyroidism and unstable CAD or uncontrolled atrial fibrillation should begin levothyroxine replacement following medical or
interventional therapy.

Myxedema crisis can be treated with full replacement doses of oral levothyroxine. Intravenous levothyroxine may be required in some situations,
including for obtunded patients with hypercapnia requiring mechanical ventilation. Levothyroxine sodium 500 mcg is given intravenously as a loading
dose, followed by 50–100 mcg intravenously daily; the lower dose is given to patients with suspected CAD. In patients with severe myxedema crisis,
liothyronine (T3, Triostat) can be given intravenously with a loading bolus of 10–20 mcg, followed by 10 mcg intravenous boluses every 8–12 hours for
the first 48 hours. Patients with hypothermia are warmed only with blankets, since faster warming can precipitate cardiovascular collapse. Patients
with hypoglycemia are given 5% dextrose intravenously.

Hyponatremia in any hypothyroid patient requires evaluation for adrenal insufficiency; serum glucose and triglyceride levels are assayed to screen
for dilutional hyponatremia. Medications and hypotonic intravenous solutions that can cause or aggravate hyponatremia are discontinued. Patients
who are mildly symptomatic with a serum sodium 120–129 mEq/mL are treated with fluid restriction, unless they are dehydrated. Symptomatic
patients with a serum sodium 120–129 mEq/mL must be managed as an inpatient (see Part 23, Hyponatremia) and are administered 0.9% NaCl
intravenously at 125 mL/h to correct hypovolemia. Hypothyroid patients with a serum sodium below 120 mEq/mL are treated with boluses of 100 mL of
3% NaCl intravenously with intravenous furosemide 20–40 mg to promote water diuresis; serum sodium levels must be monitored closely and boluses
of 3% NaCl can be repeated about every 6 hours until the serum sodium rises to 120 mmol/L or higher. When giving intravenous saline to
myxedematous patients, care must be taken to avoid fluid overload.

Patients with hypercapnia require mechanical assistance with ventilation. Opioid medications must be stopped or used in very low doses. Infections
must be treated aggressively. Patients in whom concomitant adrenal insufficiency is suspected are treated with hydrocortisone, 100 mg intravenously,
followed by 25–50 mg every 6–8 hours.

B. Monitoring and Optimizing Treatment of Hypothyroidism

Regular clinical and laboratory monitoring is critical to determine the optimal levothyroxine dose. After initiating levothyroxine replacement, serum
TSH, FT4, and FT3 levels are monitored monthly and the dose adjusted with an aim to normalize the serum TSH within 2 months. The patient should be
prescribed sufficient levothyroxine to restore a clinically euthyroid state; this can usually be attained by maintaining the serum TSH, FT4, and FT3 within
their reference ranges.

Pregnancy usually increases the levothyroxine dosage requirement, which may be required as early as the fifth week of gestation. Postpartum,
levothyroxine replacement requirements ordinarily return to prepregnancy level. Rifampin also increases levothyroxine dosage requirements.

Decreased levothyroxine dose requirements occur in women after delivery, after bilateral oophorectomy or natural menopause, after cessation of oral
estrogen replacement, or during therapy with GnRH agonists. Levothyroxine dosage may need to be titrated downward for patients who start taking
teduglutide for short bowel syndrome.

1. Elevated serum TSH level

For most patients, a high serum TSH indicates underreplacement with levothyroxine. However, patient nonadherence to prescribed levothyroxine is
surprisingly common;
Downloaded 2025­1­25before increasing
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islevothyroxine dosage, it is important to confirm patient compliance. For patients with CAD or recurrent
atrial fibrillation,
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Paul A. doses of levothyroxine to keep serum TSH in the high­normal or even slightly elevated
Fitzgerald range.
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Levothyroxine should be taken in the morning with water only. Increased levothyroxine dosage requirements (low serum T4 levels) can occur with
drugs that increase the hepatic metabolism of levothyroxine and with oral estrogen (Table 28–3). Amiodarone can increase or decrease levothyroxine
teduglutide for short bowel syndrome.
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1. Elevated serum TSH level

For most patients, a high serum TSH indicates underreplacement with levothyroxine. However, patient nonadherence to prescribed levothyroxine is
surprisingly common; before increasing the levothyroxine dosage, it is important to confirm patient compliance. For patients with CAD or recurrent
atrial fibrillation, it may be prudent to administer lower doses of levothyroxine to keep serum TSH in the high­normal or even slightly elevated range.

Levothyroxine should be taken in the morning with water only. Increased levothyroxine dosage requirements (low serum T4 levels) can occur with
drugs that increase the hepatic metabolism of levothyroxine and with oral estrogen (Table 28–3). Amiodarone can increase or decrease levothyroxine
dose requirements. Malabsorption of levothyroxine can be caused by GI disorders (malabsorption, atrophic gastritis); by coadministration of binding
substances, such as iron, fiber; raloxifene; sucralfate; aluminum hydroxide antacids; sevelamer; orlistat; bile acid–binding resins (cholestyramine and
colesevelam); PPIs, calcium, magnesium, milk, coffee, and soy milk. Increased levothyroxine dosing requirements have been seen with nephrotic
syndrome.

Serum TSH may be elevated transiently in acute psychiatric illness, with antipsychotics and phenothiazines, and during recovery from nonthyroidal
illness. Autoimmune disease can interfere with the assay and cause false elevations of TSH. Rarely, a high TSH can be caused by a thyrotropin­secreting
pituitary tumor or hyperplasia.

2. Normal serum TSH level

For most patients, the goal of levothyroxine replacement is to maintain the serum TSH in the low normal range (0.4–2.0 mIU/L). However, treated
patients with normal serum TSH levels have higher serum LDL cholesterol levels, lower average basal metabolic rate, and lower serum T3 levels
compared to matched euthyroid controls. This appears to explain why many treated patients continue to have subjective symptoms suggestive of mild
hypothyroidism, despite normal serum TSH levels. Such patients must be assessed for concurrent conditions, such as an adverse drug reaction,
Addison disease, depression, hypogonadism, anemia, celiac disease, or gluten sensitivity. If such conditions are not present or are treated and
hypothyroid­type symptoms persist, a serum T3 or free T3 level may be helpful. Low serum T3 levels may reflect inadequate peripheral deiodinase
activity to convert inactive T4 to active T3. Unless contraindicated by unstable angina, such patients with continued hypothyroid­type symptoms may be
carefully administered a slightly higher dose of levothyroxine to suppress the serum TSH slightly while achieving clinical euthyroidism and a serum FT3
in the lower half of the reference range. For most patients with hypothyroidism, an ideal stable maintenance dose of levothyroxine can usually be
found Some patients respond better to desiccated thyroid preparations.

3. Low or suppressed serum TSH level

A serum TSH level below the reference range (adults 0.4–4.0 mIU/L) is either “low” (0.1–0.39 mIU/L) or “suppressed” (less than 0.1 mIU/L). Clinically
euthyroid patients receiving levothyroxine who have “low” TSH levels do not have increased morbidity. However, a “suppressed” serum TSH often
indicates over­replacement with levothyroxine; such patients may have symptoms of hyperthyroidism with an increased risk for atrial fibrillation,
osteoporosis, and clinical hyperthyroidism. The differential diagnosis for a suppressed serum TSH includes hypopituitarism, severe nonthyroidal
illness, and some medications such as NSAIDs, biotin, opioids, nifedipine, verapamil, and high­dose (short­term) corticosteroids. Aside from the latter
circumstances, when the serum TSH is suppressed, the dosage of levothyroxine is reduced. However, some patients feel unmistakably hypothyroid
while taking the reduced dose of levothyroxine and have low serum T3 or free T3 levels. For such patients, a higher levothyroxine dose may be resumed
or substituted with desiccated thyroid, with close surveillance for atrial fibrillation, osteoporosis, and subtle manifestations of hyperthyroidism.

PROGNOSIS
Patients with mild hypothyroidism caused by autoimmune thyroiditis have a remission rate of 11%. With levothyroxine treatment of hypothyroidism,
return to a normal state is usually the rule, but relapses will occur if treatment is interrupted. Patients with myxedema crisis have a mortality rate of 30–
100%, with higher rates in patients with severe symptoms, particularly those requiring mechanical ventilation and treatment for hypotension.

WHEN TO REFER
Difficulty titrating levothyroxine replacement to normal TSH or clinically euthyroid state.

Any patient with significant CAD needing levothyroxine therapy.

WHEN TO
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Suspected myxedema crisis.

Hypercapnia.
WHEN TO REFER
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Difficulty titrating levothyroxine replacement to normal TSH or clinically euthyroid state. Access Provided by:

Any patient with significant CAD needing levothyroxine therapy.

WHEN TO ADMIT
Suspected myxedema crisis.

Hypercapnia.

Biondi B et al. Subclinical hypothyroidism in older individuals. Lancet Diabetes Endocrinol. 2022;10:129.
[PubMed: 34953533]

Biondi B et al. Critical approach to hypothyroid patients with persistent symptoms. J Clin Endocrinol Metab. 2023;108:2708.
[PubMed: 37071856]

Bridwell RE et al. Decompensated hypothyroidism: a review for the emergency clinician. Am J Emerg Med. 2021;39:207.
[PubMed: 33039222]

Calissendorff J et al. To treat or not to treat subclinical hypothyroidism, what is the evidence? Medicina (Kaunas). 2020;56:40.
[PubMed: 31963883]

Chaudhary S et al. Utility of myxedema score as a predictor of mortality in myxedema coma. J Endocrinol Invest. 2022;46:59.
[PubMed: 35945394]

Ettleson MD et al. Individualized therapy for hypothyroidism: is T4 enough for everyone? J Clin Endocrinol Metab. 2020;105:e3090.
[PubMed: 32614450]

Lee SY et al. Assessment and treatment of thyroid disorders in pregnancy and the postpartum period. Nat Rev Endocrinol. 2022;18:158.
[PubMed: 34983968]

Li SW et al. Management of overt hypothyroidism during pregnancy. Best Pract Res Clin Endocrinol Metab. 2020;34:101439.
[PubMed: 32616466]

McDermott MT. Hypothyroidism. Ann Intern Med. 2020;173:ITC1.

[PubMed: 32628881]

Ross DS. Treating hypothyroidism is not always easy: when to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to
levothyroxine monotherapy. J Intern Med. 2022;291:128.
[PubMed: 34766382]

Salvatore D et al. The relevance of T3 in the management of hypothyroidism. Lancet Diabetes Endocrinol. 2022;10:366.
[PubMed: 35240052]

Shakir MKM et al. Comparative effectiveness of levothyroxine, desiccated thyroid extract, and levothyroxine+liothyronine in hypothyroidism. J Clin
Endocrinol Metab. 2021;106:e4400.
[PubMed: 34185829]

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Current Medical Diagnosis & Treatment 2025

28­09: Hyperthyroidism (Thyrotoxicosis)

Paul A. Fitzgerald

Key Clinical Updates in Hyperthyroidism (Thyrotoxicosis)

The medication digoxin is a second­line agent for ventricular rate control in thyrotoxicosis­induced atrial fibrillation. It is reduced as
hyperthyroidism is corrected. Serum digoxin levels should be kept below 1.2 ng/mL, since higher levels are associated with increased mortality.

ESSENTIALS OF DIAGNOSIS

Sweating, weight loss or gain, anxiety, palpitations, loose stools, heat intolerance, menstrual irregularity.

Tachycardia; warm, moist skin; stare; tremor.

Graves disease: most common cause of hyperthyroidism; palpable goiter (sometimes with bruit) in most patients; ophthalmopathy also
common.

Amiodarone: most common cause of thyrotoxic crisis (“thyroid storm”).

Suppressed TSH in primary hyperthyroidism; usually increased T4, FT4, T3, FT3.

GENERAL CONSIDERATIONS
The term “thyrotoxicosis” refers to the clinical manifestations associated with elevated serum levels of T4 or T3 that are excessive for the individual
(hyperthyroidism).

A. Graves Disease

Graves disease is the most common cause of thyrotoxicosis. It is an autoimmune disorder, characterized by an increase in synthesis and release of
thyroid hormones. Autoantibodies, known as thyroid­stimulating immunoglobulins (TSI) or thyrotropin receptor antibodies (TRAb), bind to the TSH
receptors in the thyroid cell membranes and stimulate the gland to overproduce thyroid hormones. The presence of these antibodies distinguishes
Graves disease from autoimmune chronic lymphocytic (Hashimoto) thyroiditis. Both conditions usually have present serum antithyroid antibodies
(TPO Ab or Tg Ab or both).

Graves disease is more common in women than in men (8:1). Its usual onset is between the ages of 20 and 40 years. It may be accompanied by
infiltrative ophthalmopathy (Graves exophthalmos) and, less commonly, by infiltrative dermopathy (pretibial myxedema eFigure 28–5). The thymus
gland is typically enlarged and serum ANA levels are usually elevated. Many patients with Graves disease have a family history of either Graves disease
or Hashimoto autoimmune thyroiditis. Histocompatibility studies have shown an association with group HLA­B8 and HLA­DR3.

eFigure 28–5.

Pretibial myxedema. (Reproduced with permission from Carl Grunfeld, MD)

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or Hashimoto autoimmune thyroiditis. Histocompatibility studies have shown an association with group HLA­B8 and HLA­DR3.
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eFigure 28–5.

Pretibial myxedema. (Reproduced with permission from Carl Grunfeld, MD)

Viral infections, including infections with SARS­CoV­2, have been reported to precipitate Graves disease. Vaccinations against SARS­CoV­2 also have
triggered de novo Graves disease as well as relapses 4–30 days after infection or vaccination.

Patients with Graves disease have an increased risk of other systemic autoimmune disorders, including Sjögren syndrome, celiac disease, pernicious
anemia, Addison disease, alopecia areata, vitiligo, type 1 diabetes mellitus, hypoparathyroidism, myasthenia gravis, and cardiomyopathy.

B. Toxic Multinodular Goiter and Thyroid Nodules

Autonomous hyperfunctioning thyroid nodules that produce hyperthyroidism are known as toxic multinodular goiter (Plummer disease). They are
more prevalent among older adults and in iodine­deficient regions. A single hyperfunctioning nodule can also produce hyperthyroidism. Activating
TSH receptor mutations are responsible for some toxic nodules. Toxic multinodular goiter and Graves disease may sometimes coexist in the same
gland (Marine­Lenhart syndrome). Thyroid cancer is found in 5% of patients with toxic multinodular goiter.

C. Autoimmune (Postpartum or Silent) Thyroiditis and Subacute Thyroiditis

These conditions cause thyroid inflammation with release of stored hormone. They all produce a variable triphasic course: variable hyperthyroidism is
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Silent thyroiditis is also known as subacute lymphocytic thyroiditis or “hashitoxicosis.” It can occur spontaneously; women are affected four times
more frequently than men. About 50% have antithyroid antibodies. Silent thyroiditis can also be caused by chemotherapeutic agents (such as tyrosine
kinase inhibitors; denileukin diftitox; alemtuzumab; interferon­alpha; interleukin­2; and immune checkpoint inhibitors). Other drugs can cause silent
TSH receptor mutations are responsible for some toxic nodules. Toxic multinodular goiter and Graves disease may sometimes coexist in the same
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gland (Marine­Lenhart syndrome). Thyroid cancer is found in 5% of patients with toxic multinodular goiter.
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C. Autoimmune (Postpartum or Silent) Thyroiditis and Subacute Thyroiditis

These conditions cause thyroid inflammation with release of stored hormone. They all produce a variable triphasic course: variable hyperthyroidism is
followed by transient euthyroidism and progression to hypothyroidism (see Thyroiditis, above).

Silent thyroiditis is also known as subacute lymphocytic thyroiditis or “hashitoxicosis.” It can occur spontaneously; women are affected four times
more frequently than men. About 50% have antithyroid antibodies. Silent thyroiditis can also be caused by chemotherapeutic agents (such as tyrosine
kinase inhibitors; denileukin diftitox; alemtuzumab; interferon­alpha; interleukin­2; and immune checkpoint inhibitors). Other drugs can cause silent
thyroiditis, including lithium and amiodarone. In those with spontaneous silent thyroiditis, about 10–20% remain hypothyroid after 1 year. There is a
recurrence rate of 5–10%; this rate is higher in Japan.

Postpartum thyroiditis refers to autoimmune thyroiditis that occurs in the first 12 months postpartum and occasionally after miscarriages. See
Thyroiditis, above. About 22% of affected women experience hyperthyroidism followed by hypothyroidism, whereas 30% of such women have isolated
thyrotoxicosis and 48% have isolated hypothyroidism. The thyrotoxic phase typically occurs 2–6 weeks postpartum and lasts 2–3 months. Over 80%
have antithyroid antibodies. Most women progress to a hypothyroid phase that usually lasts a few months but that can be permanent.

Subacute thyroiditis is also known as “de Quervain” or “granulomatous” thyroiditis. It is typically caused by various viral infections. Women are
affected four times more frequently than men. Patients typically experience a viral upper respiratory infection and develop an enlarged and extremely
painful thyroid. About 50% of affected patients experience a symptomatic thyrotoxic phase that lasts 3–6 weeks. It is important to differentiate
subacute thyroiditis from infectious (suppurative bacterial) thyroiditis. About 10% remain hypothyroid after 1 year. The recurrence rate is 1–4%.

D. Medication­Induced Hyperthyroidism

1. Amiodarone­induced thyrotoxicosis (AIT)

Amiodarone causes thyrotoxicosis in about 5% of patients in the United States, with a higher incidence in iodine­deficient geographic areas.
Amiodarone is 37% iodine by weight and its metabolites have a half­life of about 100 days. In the short term, amiodarone normally increases serum
TSH (without hypothyroidism), though usually not over 20 mIU/L. Serum T4 and FT4 rise about 40% and may become elevated in clinically euthyroid
patients, while serum T3 levels typically decline. After 3 months, the serum TSH usually normalizes. Thyroid function tests (TSH, FT4, T3) should be
checked before starting amiodarone, after 3–6 months of therapy, and thereafter at least every 6 months (sooner if clinically warranted). Due to early
short­term changes, it is best to not check thyroid function tests during the first 3 months of therapy.

Amiodarone­induced thyrotoxicosis (AIT) can occur at any time during treatment and may develop several months after treatment discontinuation. It is
diagnosed when serum TSH levels are suppressed and serum T3 or FT3 levels are high or high­normal. Amiodarone is the leading cause for thyrotoxic
crisis (“thyroid storm”); however, the manifestations can be missed since amiodarone tends to cause bradycardia. Type 1 AIT is caused by the active
production of excessive thyroid hormone and typically occurs within 2–6 months after starting amiodarone. Type 2 AIT is caused by the passive release
of stored thyroid hormone and occurs an average of 30 months after starting amiodarone. A mixed/indeterminate type of AIT is caused by both
processes occurring simultaneously.

2. Iodine­induced hyperthyroidism (Basedow disease)

The recommended iodine intake for nonpregnant adults is 150 mcg/day. Higher iodine intake can precipitate hyperthyroidism in patients with nodular
goiters, autonomous thyroid nodules, or asymptomatic Graves disease, and less commonly in patients with no detectable underlying thyroid disorder.
Common sources of excess iodine include intravenous oral potassium iodine supplements, certain foods (eg, kelp, nori), topical iodinated antiseptics
(eg, povidone iodine), and medications (eg, amiodarone or potassium iodide). Intravenous iodinated radiocontrast dye can rarely induce a painful,
destructive subacute thyroiditis, similar to type 2 amiodarone­induced thyrotoxicosis.

3. Tyrosine kinase inhibitors

Silent autoimmune thyroiditis that releases stored thyroid hormone, resulting in hyperthyroidism, develops in about 3% of patients receiving
chemotherapy with tyrosine kinase inhibitors (eg, axitinib, sorafenib, sunitinib). While such hyperthyroidism may be subclinical, thyrotoxic crisis has
been reported. Hypothyroidism usually follows hyperthyroidism and occurs in 19% of patients taking these drugs.

4. Immune checkpoint inhibitor cancer therapy

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28­09:
Immune Hyperthyroidism (Thyrotoxicosis),
checkpoint inhibitor Paulagainst
therapy directed A. Fitzgerald
either PD­1/PD­L1 or CTLA­4/B7­1/B7­2 frequently precipitates autoimmune adversePage 3 / 18
reactions.
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
Thyroid autoimmunity commonly causes thyroiditis, hypothyroidism (primary or secondary), or hyperthyroidism from either passive release of thyroid
hormone or active production of thyroid hormone (Graves disease).
 Universidad Peruana de Ciencias Aplicadas
Silent autoimmune thyroiditis that releases stored thyroid hormone, resulting in hyperthyroidism, develops in about 3% of patients receiving
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chemotherapy with tyrosine kinase inhibitors (eg, axitinib, sorafenib, sunitinib). While such hyperthyroidism may be subclinical, thyrotoxic crisis has
been reported. Hypothyroidism usually follows hyperthyroidism and occurs in 19% of patients taking these drugs.

4. Immune checkpoint inhibitor cancer therapy

Immune checkpoint inhibitor therapy directed against either PD­1/PD­L1 or CTLA­4/B7­1/B7­2 frequently precipitates autoimmune adverse reactions.
Thyroid autoimmunity commonly causes thyroiditis, hypothyroidism (primary or secondary), or hyperthyroidism from either passive release of thyroid
hormone or active production of thyroid hormone (Graves disease).

E. Pregnancy, hCG­Secreting Trophoblastic Tumors, and Testicular Choriocarcinoma

Human chorionic gonadotropin (hCG) can bind to the thyroid’s TSH receptors. Very high levels of serum hCG, particularly during the first 4 months of
pregnancy may cause sufficient receptor activation to cause gestational thyrotoxicosis. About 20% of pregnant women have a low serum TSH during
pregnancy, but only 1% of such women have clinical hyperthyroidism that requires treatment. Pregnant women are more likely to have hCG­induced
thyrotoxicosis if they have high levels of serum asialo­hCG, a subfraction of hCG that has a greater affinity for TSH receptors. Such women are also
more likely to suffer from hyperemesis gravidarum. This condition must be distinguished from true Graves disease in pregnancy, which usually
predates conception and may be associated with high serum levels of TSI and antithyroid antibodies or with exophthalmos.

F. Rare Causes of Hyperthyroidism

Thyrotoxicosis factitia is due to intentional or accidental ingestion of excessive amounts of exogenous thyroid hormone. Struma ovarii is thyroid tissue
contained in about 3% of ovarian dermoid tumors and teratomas. Such ectopic thyroid tissue can produce excess thyroid hormone from thyroid
nodules or as a concomitant source of thyroid hormone excess with Graves disease. Pituitary TSH hypersecretion by a pituitary thyrotroph tumor or
hyperplasia can rarely cause hyperthyroidism; serum TSH is elevated or inappropriately normal in the presence of true thyrotoxicosis. Pituitary
hyperplasia may be detected on an MRI as a pituitary enlargement without a discrete adenoma being visible. This condition appears to be due to a
diminished feedback effect of T4 upon the pituitary. Some cases are familial. Metastatic functioning thyroid carcinoma can cause hyperthyroidism in
patients with a heavy tumor burden. Recombinant human thyroid­stimulating hormone (rhTSH) can rarely induce hyperthyroidism when it is given
prior to RAI therapy or scanning for metastatic differentiated thyroid cancer.

High levels of hCG can also cause thyrotoxicosis in some cases of pregnancies with gestational trophoblastic disease (molar pregnancy,
choriocarcinoma). Some such pregnancies have produced thyrotoxic crisis. Men have developed hyperthyroidism from high levels of serum hCG
secreted by a testicular choriocarcinoma.

CLINICAL FINDINGS
A. Symptoms and Signs

Thyrotoxicosis can produce nervousness, restlessness, heat intolerance, increased sweating, palpitations, pruritus, fatigue, muscle weakness, muscle
cramps, frequent bowel movements, weight change (usually loss), or menstrual irregularities. There may be fine resting finger tremors, moist warm
skin, fever, hyperreflexia, fine hair, and onycholysis (eFigure 28–6). Angina or atrial fibrillation may also be present, sometimes in the absence of other
thyrotoxic symptoms (apathetic hyperthyroidism). Women with postpartum thyroiditis are often asymptomatic or experience only minor symptoms,
such as palpitations, heat intolerance, and irritability. Chronic thyrotoxicosis may cause osteoporosis. Even subclinical hyperthyroidism (suppressed
serum TSH with normal FT4) may increase the risk of nonvertebral fractures. Tetany is a rare presenting symptom.

eFigure 28–6.

Onycholysis (separation of the nail from its bed) in Graves disease usually resolves spontaneously as the patient improves. (Reproduced, with
permission, from Gardner DG, Shoback D [editors]. Basic & Clinical Endocrinology, 10th ed. New York, NY: McGraw­Hill; 2018.)

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28­09: Hyperthyroidism (Thyrotoxicosis), Paul A. Fitzgerald Page 4 / 18
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
eFigure 28–6.
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Access Provided by:
Onycholysis (separation of the nail from its bed) in Graves disease usually resolves spontaneously as the patient improves. (Reproduced, with
permission, from Gardner DG, Shoback D [editors]. Basic & Clinical Endocrinology, 10th ed. New York, NY: McGraw­Hill; 2018.)

Patients with Graves disease usually have a diffusely enlarged thyroid that is frequently asymmetric and often accompanied by a bruit. However, there
may be no palpable thyroid enlargement. The thyroid gland in painful subacute thyroiditis is usually moderately enlarged and tender. There is often
dysphagia and pain that can radiate to the jaw or ear. With toxic multinodular goiter, there are usually palpable nodules. Patients with silent thyroiditis
or postpartum thyroiditis have either no palpable goiter or a small, nontender goiter.

Cardiopulmonary manifestations of thyrotoxicosis commonly include a forceful heartbeat, premature atrial contractions, and sinus tachycardia.
Patients often have exertional dyspnea. Atrial fibrillation or atrial tachycardia occurs in about 8% of patients with thyrotoxicosis, more commonly in
men, older adults, and those with ischemic or valvular heart disease. The ventricular response from the atrial fibrillation may be difficult to control.
Thyrotoxicosis can cause a thyrotoxic cardiomyopathy, and the onset of atrial fibrillation can precipitate HF. Echocardiogram reveals pulmonary artery
hypertension in about 40% of hyperthyroid patients. Even “subclinical hyperthyroidism” increases the risk for atrial fibrillation and overall mortality.
Hemodynamic abnormalities and pulmonary hypertension are reversible with restoration of euthyroidism.

Thyrotoxic crisis or “thyroid storm” is an extreme form of severe thyrotoxicosis and an immediate threat to life. The most common
manifestations are cardiac (HF, severe sinus tachycardia [60%], ventricular fibrillation [13%], MI, and cardiogenic shock), agitation or delirium (63%),
high fever, vomiting, diarrhea, dehydration, and hepatic impairment (52%). The presence of thyrotoxic crisis can be assessed by the Burch­Wartofsky
score that is based on clinical manifestations: a score less than 25 excludes thyrotoxic crisis, while a score of 25–45 indicates incipient crisis, and a
score greater than 45 indicates probable thyrotoxic crisis.

Eye manifestations that occur with hyperthyroidism are discussed in Thyroid Eye Disease, below.

Graves dermopathy (pretibial myxedema) occurs in about 3% of patients with Graves disease. It usually affects the pretibial region but can also
affect the dorsal forearms and wrists and dorsum of the feet. It is more common in patients with high levels of serum TSI and severe Graves
ophthalmopathy. Glycosaminoglycans accumulation and lymphoid infiltration occur in affected skin, which becomes erythematous with a thickened,
rough texture (eFigure 28–5).

Thyroid acropachy is a rare skeletal manifestation of Graves disease. It presents with digital clubbing, swelling of fingers and toes, and radiographic
findings of periostitis involving phalangeal and metacarpal bones. Extremity skin can become very thickened, resembling elephantiasis. Thyroid
acropachy is ordinarily associated with ophthalmopathy and thyroid dermopathy. Most affected patients are smokers. The presence of thyroid
acropachy is an indication of the severity of the autoimmunity; most patients have high serum titers of TSI.

Clinical hyperthyroidism during pregnancy has a prevalence of about 0.2%. It may commence before conception or emerge during pregnancy,
particularly the first trimester. Pregnancy can have a beneficial effect on the thyrotoxicosis of Graves disease, with decreasing antibody titers and
decreasing serum T4 levels as the pregnancy advances; about 30% of affected women experience a remission by late in the second trimester.
Undiagnosed or undertreated hyperthyroidism carries an increased risk of miscarriage, preeclampsia­eclampsia, preterm delivery, abruptio placenta,
maternal HF, and thyrotoxic crisis (thyroid storm). Such thyrotoxic crisis can be precipitated by trauma, infection, surgery, or delivery and confers a
fetal/maternal mortality rate of about 25%.

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Thyroid­stimulating 12:17 P Your
immunoglobulin IP is
(TSI, TSHrAb) crosses the placenta. If maternal serum TSI levels reach greater than 500% in the third trimester,
28­09: Hyperthyroidism (Thyrotoxicosis), Paul A. in
the risk of transient neonatal Graves disease Fitzgerald Page 5 / 18
the newborn is increased. Such thyrotoxic newborns have an increased risk of intrauterine
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
growth retardation and prematurity.

Hypokalemic periodic paralysis occurs in about 15% of Asian or American Indian men with thyrotoxicosis and is 30 times more common in men
particularly the first trimester. Pregnancy can have a beneficial effect on the thyrotoxicosis of Graves disease, with decreasing antibody titers and
decreasing serum T4 levels as the pregnancy advances; about 30% of affected women experience a remission by late inPeruana
Universidad the second
detrimester.
Ciencias Aplicadas
Undiagnosed or undertreated hyperthyroidism carries an increased risk of miscarriage, preeclampsia­eclampsia, preterm
Access Provided by: delivery, abruptio placenta,
maternal HF, and thyrotoxic crisis (thyroid storm). Such thyrotoxic crisis can be precipitated by trauma, infection, surgery, or delivery and confers a
fetal/maternal mortality rate of about 25%.

Thyroid­stimulating immunoglobulin (TSI, TSHrAb) crosses the placenta. If maternal serum TSI levels reach greater than 500% in the third trimester,
the risk of transient neonatal Graves disease in the newborn is increased. Such thyrotoxic newborns have an increased risk of intrauterine
growth retardation and prematurity.

Hypokalemic periodic paralysis occurs in about 15% of Asian or American Indian men with thyrotoxicosis and is 30 times more common in men
than women. It is marked by sudden symmetric flaccid paralysis, along with hypokalemia and hypophosphatemia, that occurs during hyperthyroidism
(often after intravenous dextrose, oral carbohydrates, or vigorous exercise) despite few, if any, of the classic signs of thyrotoxicosis. Attacks last 7–72
hours.

B. Laboratory Findings

Serum FT4, T3, FT3, and T4, thyroid resin uptake, and FT4 index are all usually increased. Sometimes the FT4 level may be normal but with an elevated
serum T3 (T3 toxicosis). The severity of the elevation of serum FT4 and FT3 levels does not always correlate with the severity of thyrotoxic
manifestations; patients with thyrotoxic crisis tend to have serum thyroid levels that are not significantly higher than those with less pronounced
symptoms. Serum T3 can be misleadingly elevated when blood is collected in tubes using a gel barrier, which causes certain immunoassays (eg,
Immulite but not AxSYM analyzers) to report falsely elevated serum total T3 levels in 24% of normal patients. Serum T4 or T3 can be elevated in other
nonthyroidal conditions (Table 28–4).

Table 28–4.
Factors that can cause misleading laboratory tests for hyperthyroidism.

High Serum T4 o r T3 Low Serum TSH

Laboratory error Laboratory error

Collection vial contains gel barrier for T3 African descent (3–4%)

Acute psychiatric problems (30%) Autonomous thyroid or thyroid nodule

Acute or chronic active hepatitis, primary biliary cirrhosis Corticosteroids (short­term use)
AIDS (increased TBG) Drugs

Autoimmunity Amphetamines

Euthyroid sick Biotin supplements (certain assays)

Familial thyroid­binding abnormalities Calcium channel blockers (nifedipine, verapamil)
Familial resistance to thyroid (Refetoff syndrome) Dobutamine
Pregnancy: morning sickness, hyperemesis gravidarum Dopamine

Drugs Dopamine agonists

Amiodarone Glucocorticoids
Amphetamines Metformin
Biotin supplements (certain assays) Somatostatin analogs

Capecitabine Thyroid hormone

Clofibrate Elderly euthyroid

Estrogens (oral) hCG­secreting trophoblastic tumors
Heparin Hypopituitarism

Heroin, methadone Nonthyroidal illness (severe)

Perphenazine Pregnancy (especially with morning sickness)

Tamoxifen Suppression after recent therapy for hyperthyroidism
Thyroid hormone therapy (excessive or factitious) TSH variants not detected by commercial assays

hCG, human chorionic gonadotropin; T4, levothyroxine; T3, triiodothyronine; TBG, thyroid­binding globulin.

Serum TSH is 2025­1­25

Downloaded suppressed12:17
in hyperthyroidism
P Your IP is (except in the very rare cases of pituitary inappropriate secretion of thyrotropin). Serum TSH may be
28­09: Hyperthyroidism (Thyrotoxicosis), Paul A. Fitzgerald
misleadingly low in other nonthyroidal conditions (Table 28–4). The term “subclinical hyperthyroidism” is used to describe individualsPage with a6 low
/ 18
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serum TSH but normal serum levels of FT4 and T3; in such patients, the overall prevalence of symptomatic hyperthyroidism is 0.7–1.8% in iodine­
sufficient patients and 2–15% in patients with iodine deficiency. About two­thirds of patients with subclinical hyperthyroidism have serum TSH levels
manifestations; patients with thyrotoxic crisis tend to have serum thyroid levels that are not significantly higher than those with less pronounced
symptoms. Serum T3 can be misleadingly elevated when blood is collected in tubes using a gel barrier, which Universidad Peruana
causes certain de Ciencias(eg,
immunoassays Aplicadas
Access Provided by:
Immulite but not AxSYM analyzers) to report falsely elevated serum total T3 levels in 24% of normal patients. Serum T4 or T3 can be elevated in other
nonthyroidal conditions (Table 28–4).

Table 28–4.
Factors that can cause misleading laboratory tests for hyperthyroidism.

High Serum T4 o r T3 Low Serum TSH

Laboratory error Laboratory error

Collection vial contains gel barrier for T3 African descent (3–4%)

Acute psychiatric problems (30%) Autonomous thyroid or thyroid nodule

Acute or chronic active hepatitis, primary biliary cirrhosis Corticosteroids (short­term use)
AIDS (increased TBG) Drugs

Autoimmunity Amphetamines

Euthyroid sick Biotin supplements (certain assays)

Familial thyroid­binding abnormalities Calcium channel blockers (nifedipine, verapamil)
Familial resistance to thyroid (Refetoff syndrome) Dobutamine
Pregnancy: morning sickness, hyperemesis gravidarum Dopamine

Drugs Dopamine agonists

Amiodarone Glucocorticoids
Amphetamines Metformin
Biotin supplements (certain assays) Somatostatin analogs

Capecitabine Thyroid hormone

Clofibrate Elderly euthyroid

Estrogens (oral) hCG­secreting trophoblastic tumors
Heparin Hypopituitarism

Heroin, methadone Nonthyroidal illness (severe)

Perphenazine Pregnancy (especially with morning sickness)

Tamoxifen Suppression after recent therapy for hyperthyroidism
Thyroid hormone therapy (excessive or factitious) TSH variants not detected by commercial assays

hCG, human chorionic gonadotropin; T4, levothyroxine; T3, triiodothyronine; TBG, thyroid­binding globulin.

Serum TSH is suppressed in hyperthyroidism (except in the very rare cases of pituitary inappropriate secretion of thyrotropin). Serum TSH may be
misleadingly low in other nonthyroidal conditions (Table 28–4). The term “subclinical hyperthyroidism” is used to describe individuals with a low
serum TSH but normal serum levels of FT4 and T3; in such patients, the overall prevalence of symptomatic hyperthyroidism is 0.7–1.8% in iodine­
sufficient patients and 2–15% in patients with iodine deficiency. About two­thirds of patients with subclinical hyperthyroidism have serum TSH levels
of 0.1–0.4 mIU/L (mild subclinical hyperthyroidism), while the remainder have serum TSH levels below 0.1 mIU/L (severe subclinical hyperthyroidism).

Hyperthyroidism can cause hypercalcemia, increased liver enzymes, increased alkaline phosphatase, anemia, and neutropenia. Hyperthyroidism also
increases urinary magnesium excretion, which can lead to hypomagnesemia, functional hypoparathyroidism with hypocalcemia, and tetany (rarely).
Hypokalemia and hypophosphatemia occur in thyrotoxic periodic paralysis.

Problems of diagnosis occur in patients with acute psychiatric disorders; about 30% of these patients have elevated serum T4 levels without clinical
thyrotoxicosis. The TSH is not usually suppressed, distinguishing psychiatric disorder from true hyperthyroidism. T4 levels return to normal gradually.

In Graves disease, serum thyroid­stimulating immunoglobulin (TSI, TSHrAb) is usually detectable (65%). Very high serum TSI levels predispose to
Graves ophthalmopathy. Serum TSH levels above 350 mIU/L can potentially cause false­positive TSI results. TPO Ab or Tg Ab are usually elevated but
are nonspecific. Serum ANA are also usually elevated without any evidence of SLE or other rheumatologic disease.

With painful subacute thyroiditis, patients often have an increased WBC, ESR, and CRP. About 25% have antithyroid antibodies (usually in low titer)
and serum TSI (TSHrAb) levels are normal. Patients with iodine­induced hyperthyroidism have undetectable serum TSI (or TSHrAb), no serum TPO Ab,
Downloaded 2025­1­25
and an elevated 12:17 concentration.
urinary iodine P Your IP is In thyrotoxicosis factitia, serum thyroglobulin levels are low, distinguishing it from other causes of
28­09: Hyperthyroidism (Thyrotoxicosis), Paul A. Fitzgerald Page 7 / 18
hyperthyroidism.
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With hyperthyroidism during pregnancy, women have an elevated serum total T4 and FT4 while the TSH is suppressed. An apparent lack of full
In Graves disease, serum thyroid­stimulating immunoglobulin (TSI, TSHrAb) is usually detectable (65%). Very high serum TSI levels predispose to
Universidad Peruana de Ciencias Aplicadas
Graves ophthalmopathy. Serum TSH levels above 350 mIU/L can potentially cause false­positive TSI results. TPO Ab or Tg Ab are usually elevated but
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are nonspecific. Serum ANA are also usually elevated without any evidence of SLE or other rheumatologic disease.

With painful subacute thyroiditis, patients often have an increased WBC, ESR, and CRP. About 25% have antithyroid antibodies (usually in low titer)
and serum TSI (TSHrAb) levels are normal. Patients with iodine­induced hyperthyroidism have undetectable serum TSI (or TSHrAb), no serum TPO Ab,
and an elevated urinary iodine concentration. In thyrotoxicosis factitia, serum thyroglobulin levels are low, distinguishing it from other causes of
hyperthyroidism.

With hyperthyroidism during pregnancy, women have an elevated serum total T4 and FT4 while the TSH is suppressed. An apparent lack of full
TSH suppression in hyperthyroidism can be seen due to misidentification of hCG as TSH in certain assays. The serum FT4 assay is difficult to interpret
in pregnancy. Although the serum T4 is elevated in most pregnant women, values over 20 mcg/dL (257 nmol/L) are encountered only in
hyperthyroidism. The T3 resin uptake, which is low in normal pregnancy because of high thyroxine­binding globulin (TBG) concentration, is normal or
high in thyrotoxic persons.

Since high levels of T4 and FT4 are normally seen in patients taking amiodarone, a suppressed TSH must be present along with a greatly elevated T4
(greater than 20 mcg/dL [257 nmol/L]) or T3 (greater than 200 ng/dL [3.1 nmol/L]) in order to diagnose hyperthyroidism. In type 1 amiodarone­induced
thyrotoxicosis, the presence of proptosis and serum TSI (TSHrAb) is diagnostic. In type 2 amiodarone­induced thyrotoxicosis, serum levels of
interleukin­6 (IL­6) are usually quite elevated.

C. Radioisotope Uptake and Imaging

Note: All radioisotope testing is contraindicated during pregnancy or breastfeeding.

Radioiodine (123I ) scanning can be helpful in some situations to determine the cause of hyperthyroidism but is unnecessary for diagnosis in patients
with obvious Graves disease who have elevated serum TSI or associated Graves ophthalmopathy. A high thyroid RAI uptake is seen in Graves disease
and toxic nodular goiter. The isotope is administered orally and thyroidal RAI uptake is determined at about 4–6 hours and again at 24 hours, when a
scan is also performed. Normal RAI uptake is 3–16% at 4–6 hours and 8–35% at 24 hours; however, normal ranges vary by region. A low 123I RAI uptake
is characteristic of iodine­induced hyperthyroidism and thyroiditis (subacute, silent, or postpartum), distinguishing them from Graves disease.
Patients with type 1 amiodarone­induced thyrotoxicosis have RAI uptake that is usually detectable, while in type 2 amiodarone­induced thyrotoxicosis,
thyroid RAI uptake is usually below 3%. Ideally, the RAI scan should include the pelvis to screen for concomitant struma ovarii (rare).

Misleadingly high thyroid RAI uptake has been reported in patients with the following conditions: kidney disease, iodine deficiency, hypochloremia,
recovery phase from subacute or silent thyroiditis, lithium carbonate therapy, estrogen therapy, phenothiazine therapy, some congenital disorders of
thyroid hormone synthesis, and following withdrawal of thiourea therapy (rebound phenomenon).

Technetium (Tc­99m) pertechnetate thyroid uptake is increased or normal with Graves disease, whereas those with thyrotoxicosis from thyroiditis
(silent, subacute, postpartum) have reduced uptake. It is not helpful to distinguish type I from type II amiodarone­induced thyrotoxicosis, since uptake
is typically reduced in both.

99mTc­sestamibi (MIBI) scanning usually shows increased uptake with type 1 amiodarone­induced thyrotoxicosis (AIT), decreased uptake in type 2
AIT, and intermediate uptake in mixed AIT.

D. Other Imaging

Thyroid ultrasound can be helpful in hyperthyroid patients with palpable thyroid nodules. Thyroid ultrasound shows a variably heterogeneous,
hypoechoic gland in thyroiditis. Color flow Doppler sonography is helpful to distinguish type 1 amiodarone­induced thyrotoxicosis (enlarged gland
with normal to increased blood flow velocity and vascularity) from type 2 amiodarone­induced thyrotoxicosis (distorted gland without increased
vascularity).

MRI and CT scanning of the orbits are the imaging methods of choice to visualize Graves ophthalmopathy affecting the extraocular muscles. Imaging is
required only in severe or unilateral cases or in euthyroid exophthalmos that must be distinguished from orbital pseudotumor, tumors, and other
lesion. Chest, CT in Graves disease often detects an enlarged thymus gland.

DIFFERENTIAL DIAGNOSIS
True thyrotoxicosis
Downloaded must12:17
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P Your IP from
is those conditions that elevate serum T4 and T3 or suppress serum TSH without affecting clinical status
28­09:
(see Table 28–4). Biotin supplements can cause A.
Hyperthyroidism (Thyrotoxicosis), Paul Fitzgerald
a false
Page 8 / 18
elevation in free T4 and total T3 and a false suppression of TSH in some assays that use a biotin­
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
streptavidin fluorescent detection system. Biotin can also cause false­positives in some assays for thyrotropin receptor antibodies (TSHrAb), resulting
in a misdiagnosis of Graves disease. Serum TSH is commonly suppressed in early pregnancy and only about 10% of pregnant women with a low TSH
required only in severe or unilateral cases or in euthyroid exophthalmos that must be distinguished from orbital pseudotumor, tumors, and other
Universidad Peruana de Ciencias Aplicadas
lesion. Chest, CT in Graves disease often detects an enlarged thymus gland.
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DIFFERENTIAL DIAGNOSIS
True thyrotoxicosis must be distinguished from those conditions that elevate serum T4 and T3 or suppress serum TSH without affecting clinical status
(see Table 28–4). Biotin supplements can cause a false elevation in free T4 and total T3 and a false suppression of TSH in some assays that use a biotin­
streptavidin fluorescent detection system. Biotin can also cause false­positives in some assays for thyrotropin receptor antibodies (TSHrAb), resulting
in a misdiagnosis of Graves disease. Serum TSH is commonly suppressed in early pregnancy and only about 10% of pregnant women with a low TSH
have clinical hyperthyroidism.

States of hypermetabolism without thyrotoxicosis—notably severe anemia, leukemia, polycythemia, cancer, and pheochromocytoma—rarely cause
confusion. Acromegaly may also produce tachycardia, sweating, and thyroid enlargement.

The differential diagnosis for thyroid­associated ophthalmopathy includes an orbital tumor (eg, lymphoma) or pseudotumor. Ocular myasthenia
gravis is another autoimmune condition that occurs more commonly in Graves disease but is usually mild, often with unilateral eye involvement.
Acetylcholinesterase receptor antibody (AChR Ab) levels are elevated in only 36% of such patients, and a thymoma is present in 9%.

Diabetes mellitus and Addison disease may coexist with thyrotoxicosis and can aggravate the weight loss, fatigue, and muscle weakness seen with
hyperthyroidism.

COMPLICATIONS
Hypercalcemia, osteoporosis, and nephrocalcinosis may occur in hyperthyroidism. Decreased libido, erectile dysfunction, diminished sperm motility,
and gynecomastia may be noted in men. Other complications include cardiac arrhythmias and HF, thyroid crisis, ophthalmopathy, dermopathy, and
thyrotoxic hypokalemic periodic paralysis.

TREATMENT
A. Treatment of Graves Disease

Table 28–5 outlines the treatment options for hyperthyroidism.

Table 28–5.

Medications for the treatment of hyperthyroidism.1

Medication Dose and Frequency Indications

Propranolol ER Dose: 60–80 mg orally once daily, increasing every 3 Symptomatic relief of tachycardia, tremor, diaphoresis,
days until heart rate < 90 beats per minute. anxiety
Maximum dose: 320 mg daily Thyrotoxic crisis
Hypokalemic periodic paralysis

Thiourea:
Methimazole Initial dose: usually 30–60 mg orally once daily Young adults
Dose may be divided and given twice daily to avoid GI Older adult patients
upset Mild thyrotoxicosis
Lower dose of 10–20 mg for very mild symptoms Small goiter
During pregnancy or breastfeeding, dose should not Fear of isotopes
exceed 20 mg daily Precautions during pregnancy2

Propylthiouracil (PTU) Dose: 300–600 mg orally daily in four divided doses

During pregnancy or breastfeeding, dose should not Precautions during pregnancy2
exceed 200 mg daily

Iodinated
Downloaded contrast agents
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is dose: 500 mg orally twice daily for 3 days Effective temporary treatment of thyrotoxicosis,
28­09:Iopanoic acid or ipodate
Hyperthyroidism sodium Maintenance
(Thyrotoxicosis), dose: 500 mg once daily
Paul A. Fitzgerald especially for patients who are very symptomatic Page 9 / 18
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility
Alternative treatment for patients intolerant of thioureas

Radioactive iodine (RAI,131I) Destroys overactive thyroid tissue

TREATMENT
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A. Treatment of Graves Disease Access Provided by:

Table 28–5 outlines the treatment options for hyperthyroidism.

Table 28–5.

Medications for the treatment of hyperthyroidism.1

Medication Dose and Frequency Indications

Propranolol ER Dose: 60–80 mg orally once daily, increasing every 3 Symptomatic relief of tachycardia, tremor, diaphoresis,
days until heart rate < 90 beats per minute. anxiety
Maximum dose: 320 mg daily Thyrotoxic crisis
Hypokalemic periodic paralysis

Thiourea:
Methimazole Initial dose: usually 30–60 mg orally once daily Young adults
Dose may be divided and given twice daily to avoid GI Older adult patients
upset Mild thyrotoxicosis
Lower dose of 10–20 mg for very mild symptoms Small goiter
During pregnancy or breastfeeding, dose should not Fear of isotopes
exceed 20 mg daily Precautions during pregnancy2

Propylthiouracil (PTU) Dose: 300–600 mg orally daily in four divided doses

During pregnancy or breastfeeding, dose should not Precautions during pregnancy2
exceed 200 mg daily

Iodinated contrast agents Initial dose: 500 mg orally twice daily for 3 days Effective temporary treatment of thyrotoxicosis,
Iopanoic acid or ipodate sodium Maintenance dose: 500 mg once daily especially for patients who are very symptomatic
Alternative treatment for patients intolerant of thioureas

Radioactive iodine (RAI,131I) Destroys overactive thyroid tissue

See text for Precautions
Avoid with thyroid eye disease (Graves ophthalmopathy)

Prednisone Initial dose: 0.5–0.7 mg/kg orally daily Type 2 amiodarone­induced thyrotoxicosis
After 2 weeks: begin to slowly taper and stop after
about 3 months

1See text for expanded discussion of these agents.

2See Treatment of Hyperthyroidism During Pregnancy­Planning, Pregnancy, and Lactation in text.

1. Propranolol

Propranolol is used for symptomatic relief of tachycardia, tremor, diaphoresis, and anxiety until the hyperthyroidism is resolved. It is the initial
treatment of choice for thyrotoxic crisis and effectively treats thyrotoxic hypokalemic periodic paralysis. Propranolol has no effect on thyroid hormone
secretion. Treatment usually starts with propranolol ER, which is given every 12 hours for severe hyperthyroidism due to accelerated metabolism of the
propranolol; it may be given once daily as hyperthyroidism improves (Table 28–5).

2. Thiourea drugs

Methimazole or PTU is generally used for young adults or patients with mild thyrotoxicosis, small goiters, or fear of isotopes. See Treatment of
Hyperthyroidism During Pregnancy­Planning, Pregnancy, and Lactation, below. Carbimazole, another thiourea that is converted to methimazole in
Downloaded 2025­1­25
vivo, is available 12:17
outside the P Your
United IP isPatients aged 65 years or older usually respond well. The drugs do not permanently damage the thyroid and
States.
28­09: Hyperthyroidism (Thyrotoxicosis), Paul A. Fitzgerald
are associated with a lower chance of posttreatment
Page 10 / 18
hypothyroidism (compared with RAI or surgery). There is a 50% chance of remission of
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hyperthyroidism with long­term thiourea therapy. A better likelihood of long­term remission occurs in patients with small goiters, mild
hyperthyroidism, those requiring small doses of thiourea, and those with serum TSI (TSHrAb) less than 2 mU/L. Remission is marked by decreasing
propranolol; it may be given once daily as hyperthyroidism improves (Table 28–5).
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2. Thiourea drugs

Methimazole or PTU is generally used for young adults or patients with mild thyrotoxicosis, small goiters, or fear of isotopes. See Treatment of
Hyperthyroidism During Pregnancy­Planning, Pregnancy, and Lactation, below. Carbimazole, another thiourea that is converted to methimazole in
vivo, is available outside the United States. Patients aged 65 years or older usually respond well. The drugs do not permanently damage the thyroid and
are associated with a lower chance of posttreatment hypothyroidism (compared with RAI or surgery). There is a 50% chance of remission of
hyperthyroidism with long­term thiourea therapy. A better likelihood of long­term remission occurs in patients with small goiters, mild
hyperthyroidism, those requiring small doses of thiourea, and those with serum TSI (TSHrAb) less than 2 mU/L. Remission is marked by decreasing
thiourea dosage requirement, until none is required. Patients whose TPO Ab and Tg Ab remain low after 2 years of therapy have only a 10% rate of
relapse. Some clinicians advocate RAI or surgery for patients with Graves disease who continue to require thiourea therapy after 1 year. There should
be no rush to discontinue thiourea therapy in favor of RAI or surgery, even after years of treatment. Thioureas may be continued long term for patients
who are tolerating them well. The exception is women with thyrotoxic Graves disease who are planning pregnancy in the near future; thyroid surgery or
RAI should be considered at least 4 months in advance of conception. Thiourea drugs are also useful for preparing nonpregnant hyperthyroid patients
for surgery and older patients for RAI treatment.

Agranulocytosis (absolute neutrophil count below 500/mcL [0.5 × 109/L]) or pancytopenia may occur abruptly in 0.4% of patients taking either
methimazole or PTU. All patients receiving thiourea therapy must be informed of the danger of agranulocytosis or pancytopenia and the need to stop
the drug and seek medical attention immediately with the onset of any infection or unusual bleeding. Nearly 85% of agranulocytosis cases occur within
90 days of commencing therapy; however, continued long­term blood test monitoring is required. Half of cases are discovered because of fever,
pharyngitis, or bleeding. There is a genetic tendency to develop agranulocytosis with thiourea therapy; if a close relative has had this adverse reaction,
other therapies should be considered. Agranulocytosis generally remits spontaneously with discontinuation of the thiourea. Recovery has not been
improved by filgrastim (granulocyte colony­stimulating factor).

Other common side effects include pruritus, allergic dermatitis, nausea, and dyspepsia. Antihistamines may control mild pruritus without
discontinuation of the drug. Since the two thiourea drugs are similar, patients who have a major allergic reaction to one should not be given the other.

The patient’s thyroid status is best monitored clinically and with serum FT4 levels. The patient may become clinically hypothyroid for 2 weeks or more
before TSH levels rise, the pituitary gland having been suppressed by the preceding hyperthyroidism. Rapid growth of a goiter usually occurs if
prolonged hypothyroidism is allowed to develop; the goiter may sometimes become massive but usually regresses rapidly with reduction or cessation
of thiourea therapy or with thyroid hormone replacement.

A . M ETHIMAZOLE

Except during the first trimester of pregnancy, methimazole is generally preferred over PTU since it is more convenient to use and is less likely to cause
fulminant hepatic necrosis. Methimazole therapy is also less likely to cause 131I treatment failure. Methimazole may also be administered twice daily to
reduce the likelihood of GI upset. Rare complications peculiar to methimazole include serum sickness, cholestatic jaundice, alopecia, nephrotic
syndrome, hypoglycemia, and loss of taste. The dosage is reduced as manifestations of hyperthyroidism resolve and as the FT4 level falls toward

normal. Following 131I therapy, the dose of methimazole is gradually reduced according to frequent thyroid function testing; most patients are able to
discontinue methimazole within 1–3 months following RAI therapy.

B . P ROPYLTHIOURACIL

Acute liver failure occurs in about 1 in 1000 patients, making PTU a second­line medication for treating patients with Graves hyperthyroidism. The
onset of severe liver toxicity varies from 3 days to 12 months after starting PTU. Therefore, PTU is ordinarily reserved for treating women actively
seeking fertility and during the first trimester of pregnancy, when it is preferred over methimazole. See Treatment of Hyperthyroidism During
Pregnancy­Planning, Pregnancy, and Lactation, below. The dosage and frequency of administration are reduced as symptoms of hyperthyroidism
resolve and the FT4 level approaches normal. Other rare complications peculiar to PTU include arthritis, lupus, aplastic anemia, thrombocytopenia,
and hypoprothrombinemia. With PTU, acute hepatitis occurs rarely and is treated with prednisone.

3. Iodinated contrast agents

Iopanoic acid (Telepaque) and ipodate sodium (Bilivist, Oragrafin) are iodinated contrast agents that inhibit peripheral 5′­monodeiodination of T4,
thereby blocking its conversion to active T3. They provide effective temporary treatment for thyrotoxicosis of any cause and are particularly useful for
patients who are
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Yourthyrotoxic
IP is (see Thyrotoxic crisis or “thyroid storm”). Within 24 hours, serum T3 levels fall an average of 62%. For
28­09: Hyperthyroidism (Thyrotoxicosis), Paul A.
patients with Graves disease, methimazole is begun Fitzgerald Page 11 / 18
first to block iodine organification; the next day, ipodate sodium or iopanoic acid may be added.
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They offer a therapeutic option for patients with subacute thyroiditis, amiodarone­induced thyrotoxicosis, T4 overdosage, and for those intolerant to
thioureas. Treatment periods of 8 months or more are possible, but efficacy tends to wane with time. In Graves disease, thyroid RAI uptake may be
3. Iodinated contrast agents Universidad Peruana de Ciencias Aplicadas
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Iopanoic acid (Telepaque) and ipodate sodium (Bilivist, Oragrafin) are iodinated contrast agents that inhibit peripheral 5′­monodeiodination of T4,
thereby blocking its conversion to active T3. They provide effective temporary treatment for thyrotoxicosis of any cause and are particularly useful for
patients who are symptomatically very thyrotoxic (see Thyrotoxic crisis or “thyroid storm”). Within 24 hours, serum T3 levels fall an average of 62%. For
patients with Graves disease, methimazole is begun first to block iodine organification; the next day, ipodate sodium or iopanoic acid may be added.
They offer a therapeutic option for patients with subacute thyroiditis, amiodarone­induced thyrotoxicosis, T4 overdosage, and for those intolerant to
thioureas. Treatment periods of 8 months or more are possible, but efficacy tends to wane with time. In Graves disease, thyroid RAI uptake may be
suppressed during treatment but typically returns to pretreatment uptake by 7 days after discontinuation of the drug, allowing 131I treatment.

4. Lithium carbonate

Thioureas are greatly preferred over lithium for the medical treatment of hyperthyroidism in Graves disease. However, lithium may be used effectively
in cases of methimazole or PTU­induced hepatic toxicity or leukopenia. Lithium should not be used during pregnancy. Most patients require
concurrent treatment with propranolol and sometimes prednisone.

5. Radioactive iodine (RAI,131I )

131I therapy destroys overactive thyroid tissue (either diffuse or toxic nodular goiter). Patients who have been treated with 131I in adulthood do not have

an increased risk of subsequent thyroid cancer, leukemia, or offspring with congenital abnormalities. Conflicting evidence has shown either no
increased risk or a slightly increased risk of subsequent solid tumor malignancies following 131I treatment for hyperthyroidism.

Precautions: Because radiation is harmful to the fetus and children, RAI should not be given to pregnant or lactating women or to mothers who lack
childcare. Women are advised to avoid pregnancy for at least 4 months following 131I therapy. A pregnancy test should be obtained within 48 hours
before therapy for any woman with childbearing potential. Men have been found to have abnormal spermatozoa for up to 6 months following 131I
therapy and are advised to use contraceptive methods during that time.

Patients may receive 131I while being symptomatically treated with propranolol ER, which is then reduced in dosage as hyperthyroidism resolves.
Radioiodine therapy fails to fully correct hyperthyroidism in about 20% of patients, particularly those with larger glands, very high free T4 levels, and

prior thiourea therapy. However, therapy with 131I will usually be effective if methimazole is discontinued at least 3–4 days before RAI therapy. Prior to
131I therapy, patients are instructed against receiving intravenous iodinated contrast and should consume a low­iodine diet.

The presence of Graves ophthalmopathy is a relative contraindication to 131I therapy. Following 131I treatment for hyperthyroidism, Graves
ophthalmopathy appears or worsens in 15% of patients (23% in cigarette smokers and 6% in nonsmokers) and improves in none. During treatment
with methimazole, ophthalmopathy worsens in 3% and improves in 2% of patients. Therefore, patients with Graves ophthalmopathy who are to be
treated with 131I should be considered for prophylactic prednisone (20–40 mg orally daily) for 2 months following administration of 131I; among
patients receiving prednisone following 131I treatment, preexistent ophthalmopathy improves in 67% and worsens in none.

Cigarette use increases the risk of having a flare in ophthalmopathy following 131I treatment and also reduces the effectiveness of prednisone
treatment. Patients who smoke cigarettes are strongly encouraged to quit prior to 131I treatment. Smokers receiving 131I should be considered for
prophylactic prednisone.

FT4 levels may sometimes drop within 2 months after 131I treatment, but then rise again to thyrotoxic levels, at which time thyroid RAI uptake is low.
This phenomenon is caused by a release of stored thyroid hormone from injured thyroid cells and does not indicate a treatment failure. In fact, serum
FT4 then falls abruptly to hypothyroid levels.

There is a high incidence of hypothyroidism in the months to years after 131I. Patients with Graves disease treated with 131I also have an increased
lifetime risk of developing hyperparathyroidism, particularly when 131I therapy was administered in childhood or adolescence. Lifelong clinical follow­
up is mandatory, with measurements of serum TSH, FT4, and calcium when indicated.

6. Thyroid surgery

Surgery may be indicated for patients with Graves disease who are intolerant to thioureas, women planning pregnancy in the near future, patients who
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choose not to have RAI therapy,
28­09: Hyperthyroidism and patients
(Thyrotoxicosis), with
Paul A. Graves ophthalmopathy. The surgical procedure of choice is a total resection of one lobe
Fitzgerald and12
Page a / 18
subtotal resection
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• Privacy (Hartley–Dunhill
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results in a 9% recurrence rate of hyperthyroidism.
lifetime risk of developing hyperparathyroidism, particularly when 131I therapy was administered in childhood or adolescence. Lifelong clinical follow­
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up is mandatory, with measurements of serum TSH, FT4, and calcium when indicated.
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6. Thyroid surgery

Surgery may be indicated for patients with Graves disease who are intolerant to thioureas, women planning pregnancy in the near future, patients who
choose not to have RAI therapy, and patients with Graves ophthalmopathy. The surgical procedure of choice is a total resection of one lobe and a
subtotal resection of the other lobe, leaving about 4 g of thyroid tissue (Hartley–Dunhill operation). Subtotal thyroidectomy of both lobes ultimately
results in a 9% recurrence rate of hyperthyroidism.

Patients are ordinarily rendered euthyroid preoperatively with a thiourea drug (Table 28–5). Propranolol ER is given until the heart rate is less than 90
beats per minute and continued until the serum T3 (or free T3) is normal preoperatively. If a patient undergoes surgery while thyrotoxic, larger doses of
propranolol are given perioperatively to reduce the likelihood of thyroid crisis. Ipodate sodium or iopanoic acid may be used in addition to a thiourea
to accelerate the decline in serum T3. The patient should be euthyroid by the time of surgery.

To reduce thyroid vascularity preoperatively, the patient may be treated for 3–10 days preoperatively with oral potassium iodide 25–50 mg (eg,
ThyroShield 65 mg/mL, 0.5 mL, or SSKI 1 g/mL, 1 drop) three times daily. However, preoperative potassium iodide often increases the volume of the
thyroid, so the requirement for preoperative potassium iodide for Graves disease is debatable. Preoperative iodide supplementation is not
recommended prior to surgery for multinodular goiter.

The risks of subtotal or total thyroidectomy includes damage to a recurrent laryngeal nerve, with resultant vocal fold paralysis. If both recurrent
laryngeal nerves are damaged, airway obstruction may develop, and the patient may require intubation and tracheostomy. Hypoparathyroidism also
occurs; serum calcium levels must be checked postoperatively. Patients should be admitted for thyroidectomy surgery for at least an overnight
observation period. When a competent, experienced neck surgeon performs a thyroidectomy, surgical complications are uncommon.

B. Treatment of Toxic Solitary Thyroid Nodules

Toxic solitary thyroid nodules are usually benign but may rarely be malignant. If a nonsurgical therapy is elected, the nodule should be evaluated with a
fine­needle aspiration (FNA) biopsy. Medical therapy for hyperthyroidism caused by a single hyperfunctioning thyroid nodule may be treated
symptomatically with propranolol ER and methimazole or PTU, as in Graves disease (Table 28–5). The dose of methimazole should be adjusted to keep
the TSH slightly suppressed, so the risk of TSH­stimulated growth of the nodule is reduced. Surgical treatment is usually recommended for patients
under age 40 years, for healthy older patients with toxic solitary thyroid nodules, and for nodules that are suspicious for malignancy. Patients are made
euthyroid with a thiourea preoperatively and given several days of iodine, ipodate sodium, or iopanoic acid before surgery. Postoperative
hypothyroidism usually resolves spontaneously, but permanent hypothyroidism occurs in about 14% of patients by 6 years after surgery. 131I therapy
may be offered to patients with a toxic solitary nodule who are over age 40 or in poor health (see Precautions for RAI use, above).

If the patient has been receiving methimazole preparatory to 131I, the TSH should be kept slightly suppressed in order to reduce the uptake of 131I by
the normal thyroid. Nevertheless, permanent hypothyroidism occurs in about one­third of patients by 8 years after 131I therapy. The nodule remains
palpable in 50% and may grow in 10% of patients after 131I.

C. Treatment of Toxic Nodular Goiter

Medical therapy for patients with toxic nodular goiter consists of propranolol ER (while hyperthyroid) and a thiourea, as in Graves disease (Table 28–
5). Thioureas (methimazole or PTU) reverse hyperthyroidism but do not shrink the goiter. There is a 95% recurrence rate if the drug is stopped.

Surgical therapy is the definitive treatment for a large toxic nodular goiter, following therapy with a thiourea to render them euthyroid. Surgery is
particularly indicated to relieve pressure symptoms or for cosmetic indications. Patients with toxic nodular goiter are not treated preoperatively with
potassium iodide. Total or near­total thyroidectomy is recommended, since surgical pathology reveals unsuspected differentiated thyroid cancer in
18.3% of cases.

131I therapy may be used to treat patients with toxic nodular goiter. See Precautions for RAI use, above. Any suspicious nodules should be evaluated
beforehand for malignancy with FNA cytology. Patients are rendered euthyroid with methimazole, which is stopped 3–4 days before 131I therapy. The
approximate administered 131I activity (dose) can be calculated for an average­size multinodular goiter, but smaller goiters require lower mcCi/g and
larger goiters require higher mcCi/g dosing:

Administered Activity 131I (*mcCi) = 150 (planned dose to thyroid in mcCi/g) × thyroid size (g) ÷ 24 h RAI uptake (decimal)
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*Conversion
28­09: Factor for Activity
Hyperthyroidism (Dose): MBqPaul
(Thyrotoxicosis), = mcCi × 0.037
A. Fitzgerald Page 13 / 18
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The patient follows a low­iodine diet in order to enhance the thyroid gland’s uptake of 131I, which may be relatively low in this condition (compared to
Graves disease). Relatively high doses of 131I are usually required. Hypothyroidism can occur but less commonly than seen with RAI therapy for Graves
131Itherapy may be used to treat patients with toxic nodular goiter. See Precautions for RAI use, above. Any suspicious nodules should be evaluated
beforehand for malignancy with FNA cytology. Patients are rendered euthyroid with methimazole, which isUniversidad
stopped 3–4Peruana de Ciencias
days before Aplicadas
131I therapy. The
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approximate administered 131I activity (dose) can be calculated for an average­size multinodular goiter, but smaller goiters require lower mcCi/g and
larger goiters require higher mcCi/g dosing:

Administered Activity 131I (*mcCi) = 150 (planned dose to thyroid in mcCi/g) × thyroid size (g) ÷ 24 h RAI uptake (decimal)

*Conversion Factor for Activity (Dose): MBq = mcCi × 0.037

The patient follows a low­iodine diet in order to enhance the thyroid gland’s uptake of 131I, which may be relatively low in this condition (compared to
Graves disease). Relatively high doses of 131I are usually required. Hypothyroidism can occur but less commonly than seen with RAI therapy for Graves
disease. Recurrent thyrotoxicosis can occur, so patients must be monitored closely. Peculiarly, in about 1–5% of patients with diffusely nodular toxic
goiter, the administration of 131I therapy may induce Graves disease. Also, Graves ophthalmopathy has occurred rarely following 131I therapy for
multinodular goiter.

D. Treatment of Hyperthyroidism from Thyroiditis

Patients with thyroiditis (subacute, postpartum, or silent) are treated with propranolol during the hyperthyroid phase, which usually subsides
spontaneously within weeks to months. For symptomatic relief, begin propranolol ER until the heart rate is less than 90 beats per minute (Table 28–5).
Ipodate sodium or iopanoic acid, 500 mg orally daily, promptly corrects elevated T3 levels and is continued for 15–60 days until the serum FT4 level
normalizes. Thioureas are ineffective since thyroid hormone production is actually low in this condition. Patients are monitored carefully for the
development of hypothyroidism and treated with levothyroxine as needed. With subacute thyroiditis, pain can usually be managed with NSAIDs and
corticosteroids, but opioid analgesics are sometimes required.

E. Treatment of Hyperthyroidism During Pregnancy­Planning, Pregnancy, and Lactation

Due to the increased risk of congenital anomalies with every thiourea, all women who are planning to become pregnant are encouraged to consider
definitive therapy with 131I or surgery well before conception. Both men and women who are planning pregnancy should not have 131I treatment within
about 4 months of conception. See Precautions for RAI use, above. Dietary iodine must not be restricted for such women to protect the fetus from
iodine deficiency.

First­trimester fetal exposure to thioureas (methimazole or PTU) increases the risk of birth defects by about 2%. The fetal anomalies associated with
PTU are typically less severe than those associated with methimazole; therefore, PTU is the preferred thiourea for women actively seeking fertility and
during the first trimester of pregnancy, despite the very low risk for hepatic necrosis. The most common fetal anomalies from PTU are preauricular and
branchial sinus cysts and fistulas, renal cysts, hydronephrosis, intestinal bands with intestinal malrotation, and hypospadias; these anomalies are
usually minor and surgically correctable. Women should be treated with PTU immediately prepregnancy and through the first trimester; during
pregnancy, the dose of PTU is kept below 200 mg daily to avoid goitrous hypothyroidism in the infant. PTU can be switched to methimazole in the
second trimester (see Thiourea drugs, above). Thiourea should be given in the smallest dose possible, permitting mild subclinical hyperthyroidism to
occur, since it is usually well tolerated. About 30% of women with Graves disease experience a remission by the late second trimester.

Both PTU and methimazole cross the placenta and can induce hypothyroidism, with fetal TSH hypersecretion and goiter. Fetal ultrasound at 20–32
weeks’ gestation can visualize any fetal goiter, allowing fetal thyroid dysfunction to be diagnosed and treated. Thyroid hormone administration to the
mother does not prevent hypothyroidism in the fetus, since T4 and T3 do not freely cross the placenta. Fetal hypothyroidism is rare if the mother’s
hyperthyroidism is controlled with small daily doses of PTU (50–150 mg/day orally) or methimazole (5–15 mg/day orally). Serum total T4 levels during
pregnancy should be kept at about 1.5 × the prepregnancy level. Maternal serum TSI levels over 500% at term predict an increased risk of neonatal
Graves disease in the infant.

Subtotal thyroidectomy is indicated for pregnant women with Graves disease or for fertile women of reproductive age who are sexually active and
decline contraceptives, under the following circumstances: (1) severe adverse reaction to thioureas; (2) high dosage requirement for thioureas
(methimazole greater than or equal to 30 mg/day or PTU greater than or equal to 450 mg/day); or (3) uncontrolled hyperthyroidism due to
nonadherence to thiourea therapy. Surgery is best performed during the second trimester.

Both methimazole and PTU are secreted in breast milk but not in amounts that affect the infant’s thyroid hormone levels. No adverse reactions to these
drugs have been reported in breast­fed infants. See Table 28–5 for recommended doses. It is recommended that the medication be taken just after
breastfeeding.

F. Treatment
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methimazole, iopanoic acid or sodium ipodate may be added to the regimen to further block conversion of T4 to T3 until the thyrotoxicosis is resolved.
If iopanoic acid or sodium ipodate is not available, potassium perchlorate may be given in doses of less than or equal to 1000 mg daily (in divided
nonadherence to thiourea therapy. Surgery is best performed during the second trimester.
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Both methimazole and PTU are secreted in breast milk but not in amounts that affect the infant’s thyroid hormone levels. No adverse reactions to these
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drugs have been reported in breast­fed infants. See Table 28–5 for recommended doses. It is recommended that the medication be taken just after
breastfeeding.

F. Treatment of Amiodarone­Induced Thyrotoxicosis (AIT)

Patients with either type 1 or type 2 AIT require treatment with propranolol ER for symptomatic relief and methimazole (Table 28–5). After two doses of
methimazole, iopanoic acid or sodium ipodate may be added to the regimen to further block conversion of T4 to T3 until the thyrotoxicosis is resolved.
If iopanoic acid or sodium ipodate is not available, potassium perchlorate may be given in doses of less than or equal to 1000 mg daily (in divided
doses) for a course not to exceed 30 days to avoid the complication of aplastic anemia. Amiodarone may be withdrawn but this does not have a
significant therapeutic impact for several months because of its long half­life. For patients with type 1 AIT, therapy with 131I may be successful, but only
for those with sufficient RAI uptake. Patients with type 2 AIT are usually also treated with prednisone for about 2 weeks, which is slowly tapered and
withdrawn after about 3 months. Subtotal thyroidectomy should be considered for patients with AIT that is resistant to treatment.

G. Treatment of Complications

1. Thyroid eye disease

See Thyroid Eye Disease (Graves Ophthalmopathy below).

2. Cardiac complications

A . SINUS TACHYCARDIA

Treatment consists of treating the thyrotoxicosis. A beta­blocker such as propranolol is used in the interim unless there is an associated
cardiomyopathy.

B . ATRIAL FIBRILLATION

Hyperthyroidism must be treated immediately. Other drugs, including digoxin, beta­blockers, and anticoagulants, may be required. Electrical
cardioversion is unlikely to convert atrial fibrillation to normal sinus rhythm while the patient is thyrotoxic. Spontaneous conversion to normal sinus
rhythm occurs in 62% of patients with return of euthyroidism, but that likelihood decreases with age. Following conversion to euthyroidism, there is a
60% chance that atrial fibrillation will recur, despite normal thyroid function tests. Those with persistent atrial fibrillation may have elective
cardioversion following anticoagulation 4 months after resolution of hyperthyroidism.

(1) Beta­blockers

Beta­blockers will reduce the ventricular rate, but they must be used with caution in patients with HF with reduced EF. Propranolol is generally
preferred over metoprolol and other beta­blockers for thyrotoxicosis­induced atrial fibrillation. Sotalol is sometimes preferred in patients with HF and
reduced LVEF.

(2) Non­dihydropyridine calcium channel blockers (NDCC)

Diltiazem or verapamil slows the ventricular response during atrial fibrillation. However, these drugs have negative inotropic effects and must be used
with caution in patients with HF and reduced EF.

(3) Anticoagulants

Thyrotoxicosis induces a prothrombotic state and increases the risk of embolic stroke in atrial fibrillation. Anticoagulation is usually required. DOACs
are preferred over warfarin in thyrotoxicosis­induced atrial fibrillation, since DOACs are associated with a lower all­cause mortality and lower risk for
hemorrhagic complications. The doses of warfarin required in thyrotoxicosis are smaller than normal because of an accelerated plasma clearance of
vitamin K–dependent clotting factors. Higher warfarin doses are usually required as hyperthyroidism subsides. Dabigatran malabsorption has been
reported in thyrotoxicosis­induced diarrhea.

(4) D i g o x i n

Digoxin is now a second­line agent for ventricular rate control in thyrotoxicosis­induced atrial fibrillation; larger than normal doses are usually
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required in thyrotoxicosis
28­09: Hyperthyroidism because of increased
(Thyrotoxicosis), clearance
Paul A. and an increased number of cardiac cellular sodium pumps requiring inhibition.
Fitzgerald Digoxin
Page 15 / 18
doses are reduced as hyperthyroidism is corrected. Serum digoxin levels should be kept below
©2025 McGraw Hill. All Rights Reserved. Terms of Use • Privacy Policy • Notice • Accessibility 1.2 ng/mL, since higher levels are associated with
increased mortality.
vitamin K–dependent clotting factors. Higher warfarin doses are usually required as hyperthyroidism subsides. Dabigatran malabsorption has been
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reported in thyrotoxicosis­induced diarrhea.
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(4) D i g o x i n

Digoxin is now a second­line agent for ventricular rate control in thyrotoxicosis­induced atrial fibrillation; larger than normal doses are usually
required in thyrotoxicosis because of increased clearance and an increased number of cardiac cellular sodium pumps requiring inhibition. Digoxin
doses are reduced as hyperthyroidism is corrected. Serum digoxin levels should be kept below 1.2 ng/mL, since higher levels are associated with
increased mortality.

C . HEART FAILURE

Thyrotoxicosis can cause high­output HF due to extreme tachycardia, cardiomyopathy, or both. Aggressive treatment of the hyperthyroidism is
required in either case (see Thyrotoxic crisis or “thyroid storm”).

HF may also occur as a result of low­output dilated cardiomyopathy. It is uncommon and may be caused by an idiosyncratic severe toxic effect of
hyperthyroidism upon certain hearts. Cardiomyopathy may occur at any age and without preexisting cardiac disease. See Part 11 for treatment of HF
and dilated cardiomyopathy. The patient should be rendered euthyroid. However, the HF usually persists despite correction of the hyperthyroidism.

D . APATHETIC HYPERTHYROIDISM

Apathetic hyperthyroidism may present with angina pectoris. Treatment is directed at reversing the hyperthyroidism as well as providing standard
antianginal therapy. PCI or coronary artery bypass grafting can often be avoided by prompt diagnosis and treatment.

3. Thyrotoxic crisis or “thyroid storm”

ICU admission is required. A thiourea drug is given (eg, methimazole, 15–25 mg orally every 6 hours, or PTU, 150–250 mg orally every 6 hours). Ipodate
sodium (500 mg/day orally) can be helpful if begun 1 hour after the first dose of thiourea. Iodide is given 1 hour later as potassium iodide (10 drops
three times daily orally). Propranolol is given in a dosage of 0.5–2 mg intravenously every 4 hours or 20–120 mg orally every 6 hours. Hydrocortisone is
usually given in doses of 50 mg orally every 6 hours, with rapid dosage reduction as the clinical situation improves. Plasmapheresis has been
successfully used in refractory cases to directly remove thyroid hormone. Aspirin is avoided since it displaces T4 from thyroxine­binding globulin
(TBG), raising FT4 serum levels. For refractory cases, emergency surgical thyroidectomy is an option.

Supportive care is usually required, including vasopressors, mechanical ventilation, dialysis, and extracorporeal membrane oxygenation (ECMO) for
cardiogenic shock.

4. Hyperthyroidism from postpartum thyroiditis

Propranolol ER is given during the hyperthyroid phase followed by levothyroxine during the hypothyroidism phase (see Thyroiditis).

5. Graves dermopathy

Treatment involves application of a topical corticosteroid (eg, fluocinolone) with nocturnal plastic occlusive dressings. Compression stockings may
improve any associated edema.

6. Thyrotoxic hypokalemic periodic paralysis

Therapy with oral propranolol, 3 mg/kg in divided doses, normalizes the serum potassium and phosphate levels and reverses the paralysis within 2–3
hours. No intravenous potassium or phosphate is usually required. Intravenous dextrose and oral carbohydrate aggravate the condition and are to be
avoided. Therapy is continued with propranolol, 60–80 mg orally every 8 hours (or propranolol ER daily at equivalent daily dosage), along with a
thiourea drug (eg, methimazole) to treat the hyperthyroidism.

7. Thyroid acropachy

This rare complication of Graves disease is often mild and may not require therapy. More severe cases are treated with systemic immunosuppressant
therapy that may include intravenous immune globulin and rituximab.

PROGNOSIS
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Mild Graves disease may sometimes subside spontaneously. Graves disease that presents in early pregnancy has a 30% chance of spontaneous
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remission before the third trimester. The ocular, cardiac, and psychological complications can become serious and persistent even after treatment.
Permanent hypoparathyroidism and vocal cord palsy are risks of surgical thyroidectomy. Recurrences are common following thiourea therapy but also
7. Thyroid acropachy
Universidad Peruana de Ciencias Aplicadas
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This rare complication of Graves disease is often mild and may not require therapy. More severe cases are treated with systemic immunosuppressant
therapy that may include intravenous immune globulin and rituximab.

PROGNOSIS
Mild Graves disease may sometimes subside spontaneously. Graves disease that presents in early pregnancy has a 30% chance of spontaneous
remission before the third trimester. The ocular, cardiac, and psychological complications can become serious and persistent even after treatment.
Permanent hypoparathyroidism and vocal cord palsy are risks of surgical thyroidectomy. Recurrences are common following thiourea therapy but also
occur after low­dose 131I therapy or subtotal thyroidectomy. With adequate treatment and long­term follow­up, the results are usually good. However,
despite treatment for hyperthyroidism, women experience an increased long­term risk of death from thyroid disease, CVD, stroke, and fracture of the
femur. Posttreatment hypothyroidism is common. It may occur within a few months or up to several years after RAI therapy or subtotal thyroidectomy.
Patients with thyrotoxic crisis have a high mortality rate despite treatment.

Subclinical hyperthyroidism generally subsides spontaneously. Progression to symptomatic thyrotoxicosis occurs at a rate of 1–2% per year in
patients without a goiter and at a rate of 5% per year in patients with a multinodular goiter. Most patients do well without treatment and the serum TSH
usually reverts to normal within 2 years. Most such patients do not have accelerated bone loss. However, if a baseline bone density shows significant
osteopenia, bone densitometry may be performed periodically. In persons over age 60 years, serum TSH is suppressed (below 0.1 mIU/L) in 3% and
mildly low (0.1–0.4 mIU/L) in 9%. The chance of developing atrial fibrillation is 2.8% yearly in older patients with a suppressed TSH and 1.1% yearly in
those with mildly low TSH. Asymptomatic persons with very low serum TSH are monitored closely but are not treated unless atrial fibrillation or other
manifestations of hyperthyroidism develop.

WHEN TO ADMIT
Thyroid crisis.

Hyperthyroidism­induced atrial fibrillation with severe tachycardia.

Thyroidectomy.

Azizi F et al. Efficacy and safety of long­term methimazole versus radioactive iodine in the treatment of toxic multinodular goiter. Endocrinol Metab
(Seoul). 2022;37:861.
[PubMed: 36415961]

Bourcier S et al. Thyroid storm in the ICU: a retrospective multicenter study. Crit Care Med. 2020;48:83.
[PubMed: 31714398]

Brancatella A et al. Management of thyrotoxicosis induced by PD1 or PD­L1 blockade. J Endocr Soc. 2021;5:bvab093.
[PubMed: 34337277]

Chee YJ et al. SARS­CoV­2 mRNA and Graves’ disease: a report of 12 cases and review of the literature. J Clin Endocrinol Metab. 2022;107:e2324.
[PubMed: 35235663]

Griffith ML et al. Approach to the patient with thyrotoxicosis using telemedicine. J Clin Endocrinol Metab. 2020;105:dgaa373.
[PubMed: 32525973]

Gronich N et al. Cancer risk after radioactive iodine treatment for hyperthyroidism: a cohort study. Thyroid. 2020;30:243.
[PubMed: 31880205]

Kahaly GJ. Management of Graves thyroidal and extrathyroidal disease: an update. J Clin Endocrinol Metab. 2020;105:3704.
[PubMed: 32929476]

Kim BW. Does radioactive iodine therapy for hyperthyroidism cause cancer? J Clin Endocrinol Metab. 2022;107:e448.
[PubMed: 34555150]

Lee SY et al. Hyperthyroidism:

Downloaded 2025­1­25 12:17 Pa review.
Your IPJAMA.
is 2023;330: 1472.
[PubMed:
28­09: 37847271]
Hyperthyroidism (Thyrotoxicosis), Paul A. Fitzgerald Page 17 / 18
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Praw SS et al. Approach to the patient with a suppressed TSH. J Clin Endocrinol Metab. 2023;108:472.
[PubMed: 36329632]
[PubMed: 32929476]
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Access Provided by:
Kim BW. Does radioactive iodine therapy for hyperthyroidism cause cancer? J Clin Endocrinol Metab. 2022;107:e448.
[PubMed: 34555150]

Lee SY et al. Hyperthyroidism: a review. JAMA. 2023;330: 1472.

[PubMed: 37847271]

Praw SS et al. Approach to the patient with a suppressed TSH. J Clin Endocrinol Metab. 2023;108:472.
[PubMed: 36329632]

Shalaby M et al. Predictive factors of radioiodine therapy failure in Graves’ disease: a meta­analysis. Am J Surg. 2022;223:287.
[PubMed: 33865565]

McDermott MT. Hyperthyroidism. Ann Intern Med. 2020;172:ITC49

[PubMed: 32252086]

Ylli D et al. Evaluation and treatment of amiodarone­induced thyroid disorders. J Clin Endocrinol Metab. 2021;106:226.
[PubMed: 33159436]

Yu W et al. Side effects of PTU and MMI in the treatment of hyperthyroidism: a systematic review and meta­analysis. Endocr Pract. 2020;26:207.
[PubMed: 31652102]

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