Faculty of medicine

MB ChB
Living with Long Term Conditions Course
Dissertation

Title: The Patient's long term condition is: “Hypothyroidism”

Candidate Name: Mohammed Ali Hakim Walli

Consultant Tutor: Dr : Saad Majbas

Submission Date:

 Living with Long Term Conditions – DISSERTATION MARK SHEET

Student name: Mohammed Ali Hakim walli

Tutor: Saad alshbli

Learning outcomes

Integration of the patient throughout the 10 9 8 7 6 5 4 3 2 1

dissertation with regard to amount and
quality of integration.
Focussed description of the patient’s 10 9 8 7 6 5 4 3 2 1
symptoms, signs, treatment and
outcomes
Demonstrates basic science learning 10 9 8 7 6 5 4 3 2 1
(Medical, Behavioural and Sociological)
to explain the key features in the
Describes the roles and relationship
patient’s experience. 10 9 8 7 6 5 4 3 2 1
between patients and health
professionals caring for them and the
Insight intoresponsibilities.
patient’s the patient’s perspective of the 10 9 8 7 6 5 4 3 2 1
impact of the illness on them-the Triple
Diagnosis (Physical, Psychological and
Discussion
Social) of the place of screening, health 10 9 8 7 6 5 4 3 2 1
policy planning, health education and the
role of epidemiology.
Health beliefs and myths and their 10 9 8 7 6 5 4 3 2 1
relationship to the patient’s ideas,
concerns and expectations to the
Evidence to support
consultations the usehelp.
and seeking of 10 9 8 7 6 5 4 3 2 1
investigations and treatment including
research and critical appraisal.
Reflection on the experiences and future role 10 9 8 7 6 5 4 3 2 1
as a doctor (integrated throughout and not
just an add on summary)
Presentation including organisation, visual 10 9 8 7 6 5 4 3 2 1
appearance, use of appropriate illustrations.
Demonstrates quality of referencing, written
communication skills, academic writing,
enquiry
Total and(max
Mark evaluation.
possible 100). Please
check arithmetic carefully before the start of
the viva voce examination.

(Please refer to guidance supplied when allocating the final grade)

Final Grade Please tick

( )
Distinction 90% or above
Merit 70-89%
Satisfactory 45-69%
Unsatisfactory (Resubmission Required) 44% or below

Examiner Tutor: ……………………………………………… Name: …………………………………………………

(Signed) (Please print)

 I certify that this dissertation was prepared under my

supervision

Supervisor

Name: Mohammed Ali Hakim Walli

Scientific Degree:

Date:

 ‫)بسم الله الرحمن الرحيم(‬

‫)) وَمَا تَوْفِيقِي إِلاَّ بِاللّهِ عَلَيْهِ تَوَكَّلْتُ وَإِلَيْهِ أُنِيب((‬

‫صدق الله العلي العظيم‬

‫الرقآنالكريم‪/‬سورةهود‪/‬أية‪٨٨‬‬

‫‪DEDECATION‬‬

‫‪To my family, friends and all people who support‬‬

‫‪me to complete this dissertation.‬‬

‫‪4‬‬
‫
‬
‫
‬
‫
‬
‫
‬
‫
‬
 List of content: -

Summary ……………………………………………………………….………… 7

Introduction ………………………………………………………………………... 8

Clinical features …………………………………………………………………. 9

Key Features of history …………………………………………………………. 11

Basic medical Science ……………………………………………………………13

Physiology ……………………………………………………………………….23

Pathology ………………………………………………………………………….28

Psychosocial aspects ………………………………………………………………32

Health beliefs and Myths …………………………………………………………33

Investigation ……………………………………………………………………….33

Management ……………………………………………………………………….35

The role of health services ………………………………………………………...35

Scope of problem …………………………………………………………………..36

Current research …………………………………………………………………..37

Discussion ……………………………………………………………………..….38

References ……………………………………………………..………………39

List of abbreviations :

Abbreviations Meaning
TSH Thyroid Stimulation Hormone

T3 Triiodothyronine
T4 Thyroxine

CFS Chronic Fatigue Syndrome

SERCA Sarcoplasmic Reticulum (SR) Ca2+ ATPase

ATP Adenosine Triphosphate

PID Pelvic Inflammatory Disease

List of Figures :
Figures no. Page no.
1- anterior view of Thyroid gland 13

2- Thyroid gland 15&16

3- related to trachea 16&17

4- Posterior View (Artery) 19

5- Veins and lymphatic drainage 20

6- Innervation 21

7- Histology 22

8-physiology 23

9-Triiodothyronine & Thyroxine 24

10- Skeletal muscle effect 26

11- Pathophysiology 29

12- Enlarged Thyroid gland 30

13- Histopatholgy 31

14- Investigation 34

15- Medication 35

• Summary:
Living with the long term condition, is the most module I interested in because it
reinforces the communication skills of the student. Last year, they told us about
“Living With Long Term Condition“ program in our college. Students were to be
in groups to work together and Dr. Saad Al-shabli was our group tutor. he helped us
a lot in explaining the idea of the program and also encouraged me all the time .
My patient was an female with hypothyroidism . Sh e had a hard time with her
disease because she didn’t follow all advices from her doctor and she didn’t like to
take the prescribed drugs.
During contact with the patient I found some difficulties and
challenges in selecting case as patient to follow and communication with him/her.
as a lot of cases refuse to participate in this study and this follow up. I also found
many deficiencies in knowledge and skills of taking history and making
examination , as well as deficiencies in the medical records and investigations of
the patient.
So I should increase my knowledge , skills that will help me to be a good doctor.In
that dissertation I discussed the common presentation of the patient as well as
explained differential diagnoses
and how to approach patient with Hypertension.
I reviewed the clinical features, basic medical sciences ,main features,investigations
and treatment of these disease and psychosocial effects of this disease.From this
study, I learned how to link the clinical features you see in a patient with the
knowledge you have learned ,I also learned how to write medical research when I
join information from different resources.I think it is a good chance to improve our
skills and knowledge .So I hope that this study will help us to manage future
patients with better healthcare.

• Introduction:
My object for this dissertation is to discuss hypothyroidism thoroughly.
Understanding this illness from different aspects involving anatomical, biological,
physiological, pathological and even psychological and social aspects involving the
pathogenesis and management of the disease .
Hypothyroidism is a common condition of thyroid hormone deficiency, which is
readily diagnosed and managed but potentially fatal in severe cases if untreated.
Clinical manifestations of hypothyroidism range from life threatening to no signs or
symptoms. The most common symptoms in adults are fatigue, lethargy, cold
intolerance, weight gain, constipation, change in voice, and dry skin, but clinical
presentation can differ with age and sex, among other factors. The standard
treatment is thyroid hormone replacement therapy with levothyroxine. However, a
substantial proportion of patients who reach biochemical treatment targets have
persistent complaints. In this Seminar, we discuss the epidemiology, causes, and
symptoms of hypothyroidism; summarise evidence on diagnosis, treatment, and
management.
Hypothyroidism refers to the common pathological condition of thyroid hormone
deficiency. If untreated, it can lead to serious adverse health effects and ultimately
death. Because of the large variation in clinical presentation and general absence of
symptom specificity, the definition of hypothyroidism is pre-dominantly
biochemical. Overt or clinical primary hypothyroidism is defined as thyroid-
stimulating hormone (TSH) concentrations above the reference range and free
thyroxine concentrations below the reference range. Mild or subclinical
hypothyroidism, which is commonly regarded as a sign of early thyroid failure, is
defined by TSH concentrations above the reference range and free thyroxine
concentrations within the normal range.
Hypothyroidism can be classified as primary (due to thyroid hormone deficiency),
secondary (due to TSH deficiency), tertiary (due to thyrotropin-releasing hormone
deficiency), and peripheral (extra-thyroidal; panel). Central hypothyroidism
(including both secondary and tertiary) and peripheral hypothyroidism are rare and
account for less than 1% of cases.(1)

 Clinical features

• Differential Diagnosis:
Because the most frequent presenting symptoms of hypothyroidism are
nonspecific, the list of differential diagnoses is long. In addition to
diseases of other organ systems, the following thyroid disorders may
deserve consideration (2):
1) Iodine Deficiency: Iodine is a chemical element. It is found in trace amounts
in the human body, in which its only known function is in the synthesis of thyroid
hormones. Iodine is obtained primarily through the diet but is also a component of
some medications, such as radiology contrast agents, iodophor cleansers, and
amiodarone Severe iodine deficiency results in impaired thyroid hormone synthesis
and/or thyroid enlargement (goitre). Population effects of severe iodine deficiency,
termed iodine deficiency disorders (IDDs), include endemic goitre,
hypothyroidism, cretinism, decreased fertility rate, increased infant mortality, and
mental retardation.(3)
2)Addison Disease: Addison disease, or chronic
adrenocortical insufficiency, is an uncommon disorder
resulting from progressive destruction of the adrenal
cortex. More than 90% of all cases are attributable to one
of four disorders: autoimmune adrenalitis, tuberculosis, the
acquired immune deficiency syndrome (AIDS), or
metastatic cancer see this table . (4)

3) Anovulation: is when the ovaries do not release an oocyte during a

menstrual cycle. Therefore, ovulation does not take place. However, a
woman who does not ovulate at each menstrual cycle is not necessarily
going through menopause. Chronic anovulation is a common cause of
infertility. In addition to the alteration of menstrual periods and infertility,
chronic anovulation can cause or exacerbate other long term problems,
such as hyperandrogenism or osteopenia. It plays a central role in the
multiple imbalances and dysfunctions of polycystic ovary syndrome.

9



 During the first two years after menarche 50% of the menstrual cycles
could be anovulatories. (5)

4) Chronic Fatigue Syndrome (CFS): Chronic fatigue syndrome

(CFS) is a disorder characterized by unexplained profound fatigue that is
worsened by exertion. The fatigue is accompanied by cognitive
dysfunction and impairment of daily functioning that persists for more
than 6 months.CFS was originally termed myalgic encephalomyelitis
(ME) because British clinicians noted a skeletal muscle component
manifesting as chronic fatigue and an encephalitic component manifesting
as cognitive difficulties. However, this term is inappropriate because of a
lack of encephalomyelitis in laboratory and imaging studies, and myalgia
is not a core symptom of the disease. (6)

5)chronic megacolon: is an abnormal dilation of the colon (also called

the large intestine) The dilation is often accompanied by a paralysis of the
peristaltic movements of the bowel. In more extreme cases, the feces
consolidate into hard masses inside the colon, called fecalomas (literally,
fecal tumor), which can require surgery to be removed. A human colon is
considered abnormally enlarged if it has a diameter greater than 12 cm in
the cecum (it is usually less than 9 cm greater than 6.5 cm in the
rectosigmoid region and greater than 8 cm for the ascending colon. The
transverse colon is usually less than 6 cm in diameter.(7)

6)Depression: (major depressive disorder) is a common and serious

medical illness that negatively affects how you feel, the way you think and
how you act. Fortunately, it is also treatable. Depression causes feelings of
sadness and/or a loss of interest in activities once enjoyed. It can lead to a
variety of emotional and physical problems and can decrease a person’s
ability to function at work and at home.(8)

7) Dysmenorrhea: is pain or discomfort with menstruation Although

not usually a serious medical problem, it causes some degree of monthly
disability for a significant number of women. There are two forms of
dysmenorrhea: primary and secondary. Primary dysmenorrhea is caused
by the effects of excess prostaglandin (i.e., prostaglandin F2a) production
10

 in the endometrium Secondary dysmenorrhea is menstrual pain caused by

structural abnormalities or disease processes such as endometriosis,
uterine fibroids, adenomyosis, pelvic adhesions, IUDs, or PID. In women
with secondary dysmenorrhea, the pain often lasts longer than the
menstrual period; it may begin before menstrual bleeding begins; and it
may become worse during menstruation.(9)

8) Hypopituitarism (Panhypopituitarism): Clinically significant

hypopituitarism may occur with loss or absence of 75% or more of the
anterior pituitary parenchyma. It may be congenital (exceedingly rare) or
result from a wide range of acquired intrinsic abnormalities of the
pituitary. Less frequently, disorders that interfere with the delivery of
pituitary hormone–releasing factors from the hypothalamus, such as
hypothalamic tumors, cause hypofunction of the anterior pituitary.
Hypopituitarism accompanied by evidence of posterior pituitary
dysfunction in the form of diabetes insipidus (discussed later) is almost
always of hypothalamic origin. Most cases of anterior pituitary
hypofunction are caused by the Tumors and other mass lesions, Ischemic
necrosis of the anterior pituitary.(10)

• HISTORY OF THE PATIENT:

- General presentation of hypothyroidism:
Hypothyroidism commonly manifests as a slowing in physical and mental activity
but may be asymptomatic. Symptoms and signs of this disease are often subtle and
neither sensitive nor specific. Classic signs and symptoms (eg, cold intolerance,
puffiness, decreased sweating, and coarse skin) may not be present as commonly as
was once believed.(11)
Many of the more common symptoms are nonspecific and difficult to attribute to a
particular cause. Individuals can also present with obstructive sleep apnea
(secondary to macroglossia) or carpal tunnel syndrome. Women can present with

11

galactorrhea and menstrual disturbances. Consequently, the diagnosis of

hypothyroidism is based on clinical suspicion and confirmed by laboratory testing.
Myxedema coma is a severe form of hypothyroidism that results in an altered
mental status, hypothermia, bradycardia, hypercarbia, and hyponatremia.
Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present.
Myxedema coma most commonly occurs in individuals with undiagnosed or
untreated hypothyroidism who are subjected to an external stress, such as low
temperature, infection, myocardial infarction, stroke, or medical intervention (eg,
surgery or hypnotic drugs).(12)
My patient have a symptom of hypothyroidism since (2015) like menstrual cycle
disturbance , bad mode , hair loss. until before five years she diagnosed as
hypothyroidism and now she is in good health by taken a thyroxine.

- Demographic data:
Name: Saadie Jassim Mohammed
Age: 54
Gender : female
Marital status : married
Residence: City of Qassim /Babil
Occupation: housewives
Religion: Muslim

- Past medical history:

always admission to the hospital and clinics for high blood pressure, stone
in kidney and mode disturbance and hyperlipidemia.

- Drug history :
Levoxine (levothyroxine)
Losaver (losartan)
Atrovastatine
- Family history:
She has seven brothers and nine sisters, her mother was suffering from heart disease
and her sister suffers from hypothyroidism and uses thyroxine therapy, and she has
no hereditary diseases such as cancer or sudden death.

12

- Social history :
No smoking,no drinking of alcohols' .
• Physical examination:
Patient is bradycardia , cold intolerance and pale , her skin is coarsen and
hasn't sweat , her weight 60 kg and high 160 , and the doctor noticed little
enlargement of the the thyroid gland as a result the doctor send her to do
laboratory test to confirm the diagnosis , she do the test and the results
was decreased T3 , T4 in the blood , and little increase in TSH (normal:
0.5 to 5.0 mIU/L,my patient 16 mIU/L).

-Basic medical sciences :

• Anatomy:

THYROID GLAND:
The thyroid gland, brownis red and highly vascular, is placed anteriorly in
the lower neck, level with the fifth cervical to the first thoracic vertebrae.
It is unsheathed by the pretracheal layer of deep cervical fascia and
consists of right and left lobes connected by a narrow, median isthmus.It
usually weighs 25 g but this varies. The gland is slightly heavier in
females and enlarges during menstruation and pregnancy. Estimation of
the size of the thyroid gland is clinically important in the evaluation and
management of thyroid disorders and can be achieved no invasively by
means of diagnostic ultrasound. Mean thyroid volume increases with age
No significant difference in thyroid gland volume has been observed
between males and females from 8 months to 15 years. (13)

13

h­

n­

The thyroid gland lies deep to the

sternothyroid and sternohyoid muscles,
located anteriorly in the neck at the level
of the C5–T1 vertebrae. It consists
primarily of right and left lobes,
anterolateral to the larynx and trachea. A
relatively thin isthmus unites the lobes
over the trachea, usually anterior to the
second and third tracheal rings. The
thyroid gland is surrounded by a thin fibrous capsule, which sends septa
deeply into the gland. Dense connective tissue attaches the capsule to the
cricoid cartilage and superior tracheal rings. External to the capsule is a
loose sheath formed by the visceral portion of the pretracheal layer of
deep cervical fascia.(14)

• Thyroid Gland:
-Anterior view :
The lobes of the thyroid gland are approximately conical. Their ascending
apices diverge laterally to the level of the oblique lines on the laminae of
the thyroid cartilage, and their bases are level with the fourth or fifth
tracheal cartilages. Each lobe is usually 5 cm long, its greatest transverse
and anteroposterior extents being 3 cm and 2 cm, respectively.The
posteromedial aspects of the lobes are attached to the side of the cricoid
cartilage by a lateral thyroid ligament (Berry’s ligament). The isthmus
connects the lower parts of the two lobes, although occasionally it may be
absent. It measures 1.25 cm transversely and vertically, and is usually
anterior to the second and third tracheal cartilages, although it can be
higher or even sometimes lower because its site and size vary greatly. A
conical pyramidal lobe often ascends towards the hyoid bone from the
14

isthmus or the adjacent part of either lobe (more often the left). It is
occasionally detached or in two or more parts. A fibrous or fibromuscular
band, the levator of the thyroid gland, musculus levator glandulae
thyroideae, sometimes descends from the body of the hyoid to the isthmus
or pyramidal lobe.(15)
▪ The thyroid gland is a butterfly-shaped organ that sits at the front of the
neck. It is composed of two lobes, left and right, connected by a narrow
15

 isthmus The thyroid weighs 25 grams in

adults with each lobe being about 5 cm
long, 3 cm wide and 2 cm thick, and the
isthmus about 1.25 cm in height and width
The gland is usually larger in women, and
increases in size in pregnancy.
▪ The thyroid sits near the front of the neck,
lying against and around the front of the
larynx and trachea The thyroid cartilage and cricoid cartilage lie just
above the gland, below the Adam's apple. The isthmus extends from the
second to third rings of the trachea, with the uppermost part of the lobes
extending to the thyroid cartilage, and the lowermost around the fourth
to sixth tracheal rings The thyroid gland is covered by a thin fibrous
capsule which has an inner and an
outer layer.
▪ The outer layer is continuous with
the pretracheal fascia, attaching the
gland to the cricoid and thyroid
cartilages via a thickening of the
fascia to form the posterior
suspensory ligament of thyroid gland
also known as Berry's ligament, this causes the thyroid to move up and
down with swallowing, the inner layer extrudes into the gland and forms
the septae that divides the thyroid tissue into microscopic lobules.
▪ The infrahyoid muscles lie in front of the gland and the
sternocleidomastoid muscle to the side. Behind the outer wings of the
thyroid lie the two carotid arteries. The trachea, larynx, lower pharynx
and esophagus all lie behind the thyroid. In this region, the recurrent
laryngeal nerve and the inferior thyroid artery pass next to or in the
ligament.(16)
16

 -Posterior View:

• Variation in thyroid gland lobes:

There are many variants in the size and shape of the thyroid gland, and in
the position of the embedded parathyroid glands. Sometimes there is a
third lobe present called the pyramidal lobe. When present, this lobe often
stretches up the hyoid bone from the thyroid isthmus and may be one to
several divided lobes. The presence of this lobe ranges in reported studies
from 18.3% to 44.6%. It was shown to more often arise from the left side

17

and occasionally separated. The pyramidal lobe is also known as

Lalouette's pyramid. The pyramidal lobe is a remnant of the thyroglossal
duct which usually wastes away during the thyroid gland's descent. Small
accessory thyroid glands may in fact occur anywhere along the
thyroglossal duct, from the foramen cecum of the tongue to the position of
the thyroid in the adult. A small horn at the back of the thyroid lobes,
usually close to the recurrent laryngeal nerve and the inferior thyroid
artery, is called Zuckerkandl's tubercle. Other variants include a levator
muscle of thyroid gland, connecting the isthmus to the body of the hyoid
bone, and the presence of the small thyroid ima artery. (17)

18

-Vascular supply and lymphatic drainage:

• Arteries:
The thyroid gland is supplied by the superior and inferior thyroid arteries
and sometimes by an arteria thyroidea ima from the brachiocephalic trunk
or aortic arch. The arteries are large and their branches anastomose
frequently both on and in the gland, ipsilaterally and contralaterally. The
superior thyroid artery, which is closely related to the external branch of
the superior laryngeal nerve, pierces the thyroid fascia and then divides
into anterior and posterior branches. The anterior branch supplies the
anterior surface of the gland, and the posterior branch supplies the lateral
and medial surfaces. The inferior thyroid artery approaches the base of the
thyroid gland and divides into superior (ascending) and inferior thyroid
branches to supply the inferior and posterior surfaces of the gland. The
superior branch also supplies the parathyroid glands. The relationship
between the inferior thyroid artery and the recurrent laryngeal nerve is
highly variable and of considerable clinical importance; iatrogenic injury
to the nerves that supply the larynx represents a major complication of
thyroid surgery. The recurrent laryngeal nerve is usually related to the
posterior branch of the inferior thyroid artery, which may be replaced by a
vascular network. (18)

• Veins:
Three pairs of thyroid veins usually form a thyroid plexus of veins on the
anterior surface of the thyroid gland and anterior to the trachea. The
superior thyroid veins accompany the superior thyroid arteries; they drain
the superior poles of the thyroid gland; the middle thyroid veins do not
accompany but run essentially parallel courses with the inferior thyroid
arteries; they drain the middle of the lobes. The usually independent

19

 inferior thyroid veins drain the

inferior poles. The superior and
middle thyroid veins drain into the
IJVs; the inferior thyroid veins drain
into the brachiocephalic veins
posterior to the manubrium. (19)

• Lymphatic Drainage of
Thyroid Gland:
The lymphatic vessels of this gland
run in the interlobular connective
tissue, usually near the arteries; they
communicate with a capsular
network of lymphatic vessels. From
here, the vessels pass initially to
prelaryngeal, pretracheal, and
paratracheal lymph nodes. The
prelaryngeal nodes drain in turn to
the superior deep cervical lymph
nodes, and the pretracheal and
paratracheal lymph nodes drain to the inferior deep cervical nodes.
Laterally, lymphatic vessels located along the superior thyroid veins pass
directly to the inferior deep cervical lymph nodes. Some lymphatic vessels
may drain into the brachiocephalic lymph nodes or the thoracic duct. (20)

20

• Innervation:
The thyroid gland receives its
innervation from the superior,
middle and inferior cervical
sympathetic ganglia.
Postganglionic fibers from the
inferior cervical ganglion form
a plexus on the inferior thyroid
artery, which accompanies the artery to the thyroid gland, and
communicates with the recurrent laryngeal and external branch of the
superior laryngeal nerves, with the superior cardiac nerve, and with the
plexus on the common carotid artery. They reach the gland through the
cardiac and superior and inferior thyroid peri-arterial plexuses that
accompany the thyroid arteries. These fibers are vasomotor, not
secretomotor. They cause constriction of blood vessels. Endocrine
secretion from the thyroid gland is hormonally regulated by the pituitary
gland. (21)

• Histology:

The parenchyma of the thyroid is composed of millions of rounded

epithelial thyroid follicles of variable diameter, each with simple
epithelium and a central lumen densely filled with gelatinous acidophilic
colloid. The thyroid is the only endocrine gland in which a large quantity
of secretory product is stored. Moreover, storage is outside the cells, in the
colloid of the follicle lumen, which is also unusual. There is sufficient
hormone in follicles to supply the body for up to 3 months with no
additional synthesis. Thyroid colloid contains the large glycoprotein
.thyroglobulin (660 kDa), the precursor for the active thyroid hormones
21

The thyroid gland is covered by a fibrous capsule from which septa extend
into the parenchyma, dividing it into lobules and carrying blood vessels,
nerves, and lymphatics.Follicles are densely packed together, separated
from one another only by sparse reticular connective tissue, although this
stroma is very well vascularized with fenestrated capillaries for transfer of
released hormone to the blood.
The follicular cells, or thyrocytes, range in shape from squamous to low
columnar, their size and other features varying with their activity that is
controlled by thyroid-stimulating hormone (TSH) from the anterior
pituitary. Active glands have more follicles of low columnar epithelium;
glands with mostly squamous follicular cells are hypoactive.
Another endocrine cell type, the parafollicular cell or C cell, is also found
inside the basal lamina of the follicular epithelium or as isolated clusters
between follicles Secretion
of calcitonin is triggered by
elevated blood Ca2+ levels
and it inhibits osteoclast
activity, but this function in
humans is less important
than the roles of parathyroid
hormone and vitamin D in
the regulation of normal
calcium homeostasis.(22)

22
• physiology:
The thyroid gland, located anterior and
inferior to the larynx, consists of two lobes
united by an isthmus. It originates in early
embryonic life from the foregut endoderm
near the base of the developing tongue. It
synthesizes the thyroid hormones thyroxine (tetra-iodothyronine or T4
iodothyronine (T3), which help control the basal metabolic) and trirate in
cells throughout the body, as well as the polypeptide hormone calcitonin.
Production, storage, and release of thyroid hormones involve an unusual,
multistage process in the thyrocytes , with both an exocrine phase and an
endocrine phase. Both phases are promoted by TSH and occur in the same
cell. The major activities of this process include the following:

1. The production of thyroglobulin, which is

similar to that in other glycoprotein-exporting
cells, with synthesis in the rough ER and
glycosylation in the Golgi apparatus.
Thyroglobulin has no hormonal activity itself
but contains 140 tyrosyl residues critical for
thyroid hormone synthesis. The glycoprotein
is released as an exocrine product from apical
vesicles of thyrocytes into the follicular
lumen.

23

 2. The uptake of iodide from blood by Na/I symporters (NIS) in the

thyrocytes’ basolateral cell membranes, which allows for 30-fold
concentration of dietary iodide in thyroid
tissue relative to plasma.

3. Iodination of tyrosyl residues in

thyroglobulin with either one or two atoms
occurs in the colloid after oxidation of
iodide to iodine by membrane-bound
thyroid peroxidase on the microvilli
surfaces of thyrocytes.

4. Formation of T3 and T4 (also called

thyroxine) occurs as
two iodinated tyrosines, still part of
colloidal thyroglobulin, which are
covalently conjugated in coupling
reactions.

5. Endocytosis of iodinated thyroglobulin by the thyrocytes involves both

fluid-phase pinocytosis and receptormediated endocytosis. The endocytic
vesicles fuse with lysosomes, and the thyroglobulin is thoroughly
degraded by lysosomal proteases, freeing active thyroid hormone as both
T3 and T4.

6. Secretion of T4 and T3 at the basolateral domains of thyrocytes occurs

in an endocrine manner: both molecules are immediately taken up by
capillaries.(23)

• Physiological Effects of Thyroid Hormone:(24)

Thyroid hormone acts on essentially all cells and tissues, and imbalances
in thyroid function constitute some of the most common endocrine
diseases. Thyroid hormone has many direct actions, but it also acts in
24










subtler ways to optimize the actions of several other hormones and

neurotransmitters.
- Cardiovascular Effects:
Perhaps the most clinically important actions of thyroid hormone are those
on cardiovascular physiology. T3 increases cardiac output, thereby
ensuring sufficient O2 delivery to tissues, the resting heart rate and stroke
volume are increased. The speed and force of myocardial contractions are
enhanced (positive chronotropic and inotropic effects, respectively), and
the diastolic relaxation time is shortened (positive lusitropic effect),
however, thyroid hormone decreases systemic resistance by dilating
arterioles in the peripheral circulation. Total blood volume is increased by
activation of the renin-angiotensin aldosterone axis, thereby increasing
renal tubular sodium reabsorption.

- Effects on Basal Metabolic Rate and Thermogenesis:

Increased O2 use ultimately depends on an increased supply of substrates
for oxidation. T3 augments glucose absorption from the gastrointestinal
tract and increases glucose turnover (glucose uptake, oxidation, and
synthesis). In adipose tissue, thyroid hormone induces enzymes for the
synthesis of fatty acids, also enhances the clearance of chylomicrons. Thus
lipid turnover (free fatty acid release from adipose tissue and oxidation) is
augmented.
Protein turnover (release of muscle amino acids, protein degradation, and
to a lesser extent protein synthesis and urea formation) is also increased.
The overall metabolic effect of thyroid hormone has been aptly described
as accelerating the physiological response to starvation. In addition,
thyroid hormone stimulates synthesis of bile acids from cholesterol and
promotes biliary secretion.
Thyroid hormones stimulate thermogenesis by affecting both adenosine
triphosphate (ATP) utilization and the efficiency of ATP synthesis. ATP
utilization is enhanced by upregulation of several energy-dependent
processes, including Na+, K+ -ATPase and SERCA, particularly in
25

skeletal muscle, where calcium cycling between the cytoplasm and

sarcoplasmic reticulum uses ATP and generates heat.

- Respiratory Effects:
Thyroid hormone stimulates O2 delivery. Appropriately, T3 utilization and
enhances O2 increases the resting respiratory rate, minute ventilation, and
the ventilatory response to hypercapnia and hypoxia. These actions
maintain a normal arterial PO2 when O2 utilization is increased and a
normal PCO2 when CO2 production is increased. Additionally, the
hematocrit increases slightly to enhance O2-carrying capacity, This
increase results from stimulation of erythropoietin production by the
kidney.

- Skeletal Muscle Effects:

Normal function of skeletal muscles
also requires optimal amounts of
thyroid hormone. This requirement
may be related to regulation of energy
production and storage. Glycolysis
and glycogenolysis are increased,
whereas glycogen and creatine
phosphate are reduced by thyroid
hormone excess. The inability of
muscle to take up and phosphorylate
creatine leads to its increased urinary
excretion.

26

- Effects on Growth and Maturation:

A major effect of thyroid hormone is to promote growth and maturation. A
small but crucial amount of thyroid hormone crosses the placenta, and the
fetal thyroid axis becomes functional at midgestation. Thyroid hormone is
extremely important for normal neurological development and proper
bone formation in the fetus. In infants, insufficient fetal thyroid hormone
causes congenital hypothyroidism, characterized by irreversible
intellectual disability and short stature.

- Effects on Bone, Hard Tissue, and Dermis:

Thyroid hormone promotes endochondral ossification, linear bone growth,
and maturation of the epiphyseal bone centers. T3 supports the actions of
growth hormone, insulin-like growth factor (IGF)-I, and other growth
factors. T3 enhances maturation and activity of chondrocytes in the
cartilage growth plate, in part by increasing local growth factor production
and action. During linear postnatal growth, T3 also supports normal adult
bone remodeling.
- Effects on the Nervous System:
Thyroid hormone regulates the timing and pace of development of the
CNS. Thyroid hormone deficiency in utero and in early infancy inhibits
growth of the cerebral and cerebellar cortex, proliferation of axons and
branching of dendrites, synaptogenesis, myelination, and cell migration.
Irreversible CNS impairment results when neonatal thyroid hormone
deficiency is not recognized and treated promptly. Thyroid hormone also
enhances wakefulness, alertness, responsiveness to various stimuli,
auditory sense, awareness of hunger, memory, and learning capacity.
Furthermore, the speed and amplitude of peripheral nerve reflexes are
increased by thyroid hormone, as is motility of the gastrointestinal tract.

27

- Effects on Reproductive Organs and Endocrine Glands :

In both women and men, thyroid hormone plays an important permissive
role in regulation of reproductive function. The normal ovarian cycle of
follicular development, maturation, and ovulation, the homologous
testicular process of spermatogenesis, and maintenance of the healthy
pregnant state are all disrupted by significant deviations in thyroid
hormone levels from the normal range. In part these deleterious effects
may be caused by alterations in the metabolism or availability of steroid
hormones. For example, thyroid hormone stimulates hepatic synthesis and
release of sex steroid–binding globulin.

• Pathophysiology:(25)
• Chronic Lymphocytic (Hashimoto) Thyroiditis:
Hashimoto thyroiditis is the most common cause of hypothyroidism in
areas of the world where iodine levels are sufficient. It is characterized by
gradual thyroid failure secondary to autoimmune destruction of the
thyroid gland. It is most prevalent between 45 and 65 years of age and is
more common in women with a female to male ratio of 10 : 1 to 20 : 1.
Although it is primarily a disease of older women, it can occur at any age,
.including childhood

• Pathogenesis
Hashimoto thyroiditis is an autoimmune disease caused by an immune
response to thyroid auto-antigens. Circulating autoantibodies against
thyroid antigens are present in the vast majority of patients. The immune
response leads to progressive depletion of thyroid epithelial cells
associated with lymphocytic infiltrates and fibrosis. The inciting events
28

leading to the autoimmune response have not been

fully elucidated, but multiple immunologic
mechanisms that may contribute to thyroid cell
damage have been identified, including the
following:
• CD8+ cytotoxic T-cell–mediated killing of thyroid
epithelial cells.

• Cytokine-mediated cell death. T-cell activation leads

to the production of inflammatory cytokines such as
interferon-γ in the thyroid gland, with resultant
recruitment and activation of macrophages and
damage to follicles.

• Binding of anti-thyroid antibodies (anti-

thyroglobulin, and anti-thyroid peroxidase
antibodies), followed by antibody-dependent cell–
mediated cytotoxicity.

-The disease appears to have a significant genetic component, based on a

concordance rate of about 40% in monozygotic twins and the presence of
29

anti-thyroid antibodies in approximately 50% of asymptomatic siblings of

affected patients. Increased susceptibility to Hashimoto thyroiditis is
associated with polymorphisms in immune regulation– associated genes,
the most significant of which is the cytotoxic T lymphocyte–associated
antigen-4 gene (CTLA4), which codes for a negative regulator of T-cell
responses.

• Clinical features:

Hashimoto thyroiditis comes to

clinical attention as painless
enlargement of the thyroid,
usually associated with some
degree of hypothyroidism, often
in a middle-age woman. The
enlargement of the gland usually
is symmetric and diffuse, but in
some cases it may be sufficiently
localized to raise suspicion for
neoplasm. In the usual clinical
course, hypothyroidism develops gradually. In some cases, however, it
may be preceded by transient thyrotoxicosis caused by disruption of
thyroid follicles, with secondary release of thyroid hormones
(hashitoxicosis). During this phase, free T4 and T3 concentrations are
elevated, TSH is and T3 diminished, and radioactive iodine uptake is
decreased. As hypothyroidism supervenes, T4 levels progressively fall,
accompanied by a compensatory increase in TSH. Patients with
Hashimoto thyroiditis often have other autoimmune diseases and are at
increased risk for the development of B-cell non-Hodgkin lymphomas,
30

 which typically arise within the

thyroid gland. The relationship
between Hashimoto disease and
thyroid epithelial cancers remains
controversial, with some
morphologic and molecular
studies suggesting a predisposition
to papillary carcinomas.

• Histopathology:

The thyroid usually is diffusely and symmetrically enlarged. Microscopic

examination reveals widespread infiltration of the parenchyma by a
mononuclear inflammatory infiltrate containing small lymphocytes,
plasma cells, and well-developed germinal centers .The thyroid follicles
are atrophic and are lined in many areas by epithelial cells distinguished
by the presence of abundant eosinophilic, granular cytoplasm, termed
Hürthle, or oxyphil, cells. This is a metaplastic response of the normal low
cuboidal follicular epithelium to ongoing injury; on ultrastructural
examination, the Hürthle cells are characterized by numerous prominent
mitochondria. Interstitial connective tissue is increased and may be
abundant. Less commonly, the thyroid is small and atrophic as a result of
more extensive fibrosis (fibrosing variant).

31

• psychosocial aspect:

People with thyroid disorders often have emotional or mental health

symptoms as well as physical symptoms. This is especially the case for
people with hyperthyroidism (an over-active thyroid), hypothyroidism (an
under-active thyroid), thyroid related eye disease, or thyroid cancer. (26)
Thyroid dysfunction is known to have a significant impact on mental
health. Hypothyroidism, in particular, has been linked to mood disorders
and acute psychosis. Though most commonly associated with depression,
hypothyroidism has been linked to psychosis.

1) Patients sometimes report they have gained weight or that they find it
difficult to lose weight during treatment which may contribute to feelings
of low self-esteem and mood.
2) Sometimes psychological symptoms are a side-effect of the treatment.
Steroids for example can aggravate depression. Beta blockers prescribed
to slow down your heart rate and to reduce anxiety if you are hyperthyroid
can make some people feel tired, depressed, and mentally less alert.
3) A thyroid disorder can also cause changes in appearance - for example,
changes due to thyroid eye disease, weight gain or loss, or loss of hair -
which can damage your self-esteem. People may ask awkward questions
or stare, which can be distressing.
4) It is sometimes suggested that stressful life events can cause or
aggravate a thyroid disorder. If you are already experiencing stress in
other areas of life, this can of course contribute to your psychological
symptoms if you have a thyroid disorder, and they may be more
pronounced or take longer to settle.
5)hypothyroidisms patient have an idea that in future their disease
progress to be a cancer.
32

6) Some people lose motivation when it comes to daily tablet-taking or

attending clinics. Taking tablets irregularly can upset your hormone
balance and aggravate the psychological symptoms.
7)My patient has idea that she should take antidepressant medication as
well as when she in good mode because take thyroxine daily.

• Health believes and myths:

My patient thinks that “ Hypothyroidism can be controlled through diet
regulation”as most diabetic patient beliefs.
Also he believes that “I can't lose weight if I have hypothyroidism “
And she believed that it was possible to treat it through “some types of
herbs and natural honey”.
The reason behind this belief as herbalists and some groups on social
media.
Also he believes that “Once my TSH becomes normal, I can stop taking
levothyroxine tablets “ .(27)

• Investigation:
• Blood test:

Diagnosis of hypothyroidism is based on symptoms and the results of blood tests

that measure the level of TSH and sometimes the level of the thyroid hormone
thyroxine. A low level of thyroxine and high level of TSH indicate an under-active
thyroid. That's because your pituitary produces more TSH in an effort to stimulate
your thyroid gland into producing more thyroid hormone.

33

34
• Management:
Standard treatment for hypothyroidism involves daily use of the synthetic thyroid
hormone levothyroxine (Levo-T, Synthroid, others). This oral medication restores
adequate hormone levels, reversing the signs and symptoms of hypothyroidism.(28)

Treatment with levothyroxine will likely be lifelong, but because the dosage you
need may change, So my patient is check FSH test every 6 month .

• Roles of health and social care professionals:

There is a significant health professional behavioural component to the
management of hypothyroidism. Addressing the differences in patient and
professional knowledge and perceptions could reduce the barriers to
optimal treatment, while continuity of care and increased involvement of
pharmacists and practice nurses would help to promote optimal thyroid
replacement.

Although health professionals felt that hypothyroidism was easy to

manage, GPs and nurses generally revealed inadequate knowledge of
medication interactions and levothyroxine pharmacokinetics. Pharmacists
felt limited in the advice that they provide to patients due to lack of access
to patient records. Most GPs and nurses followed local guidelines, and
relied on blood tests over clinical symptoms to adjust levothyroxine dose.
35

The information exchanged between professional and patient was usually

restricted by time and often centred on symptoms rather than patient
education. Health professionals felt that incorrect levothyroxine adherence
was the main reason behind suboptimal treatment, although other factors
such as comorbidity and concomitant medication were mentioned.
Enablers perceived by health professionals to improve the management of
hypothyroidism included continuity of care, blood test reminders, system
alerts for interfering medications and prescription renewal, and accessible
blood tests and levothyroxine prescriptions for patients.

• Scope of problem:
- Epidemiology:-
The National Health and Nutrition Examination Survey (NHANES
1999-2002) of 4392 individuals reflecting the US population reported
hypothyroidism (defined as TSH levels exceeding 4.5 mIU/L) in 3.7% of
the population. (29) Hypothyroidism is more common in women with small
body size at birth and low body mass index during childhood.

Iodine deficiency as a cause of hypothyroidism is more common in less-

developed countries. Routine supplementation of salt, flour, and other
food staples with iodine has decreased the rates of iodine deficiency.

World Health Organization (WHO) data from 130 countries taken from
January 1994 through December 2006 found inadequate iodine nutrition
in 30.6% of the population. The WHO recommends urinary iodine
concentrations between 100 and 199 µg/L in the general population and a
range of 150-249 µg/L in pregnant women. In developed countries, death
caused by hypothyroidism is uncommon.

36

Age-related demographics
The frequency of hypothyroidism, goiters, and thyroid nodules increases
with age. Hypothyroidism is most prevalent in elderly populations, with
2-20% of older age groups having some form of hypothyroidism. The
Framingham study found hypothyroidism (TSH > 10 mIU/L) in 5.9% of
women and 2.4% of men older than 60 years. (30) In NHANES 1999-2002,
the odds of having hypothyroidism were 5 times greater in persons aged
80 years and older than in individuals aged 12-49 years.

Sex-related demographics
Community studies use slightly different criteria for determining
hypothyroidism; therefore, female-to-male ratios vary. Generally, the
prevalence of thyroid disease is reportedly 2-8 times higher in females.

Race-related demographics
NHANES 1999-2002 reported that the prevalence of hypothyroidism
(including the subclinical form) was higher in whites (5.1%) and Mexican
Americans than in African Americans (1.7%). African Americans tend to
have lower median TSH values.

• Current Research :
pharmacotherapy consists of single and compound drugs. Single drugs are
selected as per the constitution (Mizaj) of drugs as opposed to the abnormal
constitution (Su-e-Mizaj) of disease and its pathology. Some drugs increase
the basal metabolic rate whereas some evacuate the morbid material from
the body by the action of purgation. The drugs are used either in a single
form or as a prescription of more than one drug in the form of decoction
(Joshandah), infusion (Kheshandah), or powder (Safoof). This review aims
37

 at providing comprehensive information regarding various drugs used in

Unani system of medicine that is used in the management of thyroid
dysfunction.

• Discussion:
My patient is 52 year-old female suffering from hypothyroidism . She was
uncontrolled life style, overweight and did not care about her diet (unhealthy diet).
Regarding her prescribed treatment she does not adhered to it for first five years.
She didn’t take her medication on time and most of the time forget to take it.
Symptoms of hypothyroidism increased, and the doctor raised the dose of
medication.The investigations revealed that she has elevated blood pressure,
cholesterol and triglycerides. After I advised her and explained in a simple way
somethings about her condition, risk factors and possible complications if she
didn’t care about herself in addition to the support of her family. So, she adhered to
the medication and experienced an improvement of her condition. From this
experience, winning confidence of the patient with good communication skills, play
an important role in improving the compliance of patient.

I think there are many patients around the world who need medical information
about their diseases to increase the compliant patients and get better results. For
example, we have to develop TV programs about common diseases, their features,
management and others. Also increase the number of educational campaigns will be
beneficial in decreasing the non-compliant patients and to increase general health.
the patient and his family and the community in result get benefit from this program
no matter to what degree the benefit was.

38

 • References:
1) Medscape
https://emedicine.medscape.com/article/122393-differential
2) WebMD
https://www.webmd.com/g00/a-to-z-guides/understanding-anemia-basics?
i10c.encReferrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmlxLw%3D%3D&i10c.ua
=1&i10c.dv=14
3) Robbins basic pathology \p790
4) https://order.store.mayoclinic.com/books/gnweb43?utm_source=MC-
DotOrg-PS&utm_medium=Link&utm_campaign=FamilyHealth-
Book&utm_content=FHB&_ga=2.139508663.561622101.1647973192-11211413
89.1647633503
5) Medscape
https://emedicine.medscape.com/article/235980-overview
6) Kellerman RD, et al. Myalgic Encephalomyelitis/Chronic Fatigue
Syndrome. In: Conn's Current Therapy 2020. Elsevier; 2020. https://
www.clinicalkey.com. Accessed Feb 4, 2020.

7) Psychiatry org.
https://www.psychiatry.org/patients-families/depression/what-is-depression
8) Carol Porth - Essential of Pathophysiolog Concepts of Altered Health States
3rdEd 2011-Dr Murtadha \p1057
9) Robbins basic pathology \p754
10) Medscape
https://emedicine.medscape.com/article/122393-clinical

11)Klein, Levey GS. Unusual manifestation of hypothyroidism. Arch Intern

Med. 1984;144:123–8.

12) Doucer J, Teivalle CH, Chassagne PH, et al. Does age play a role in clinical
Presentation of hypothyroidism. J Am Geriatric Soc. 1994;42:984–6.
13) Grays Anatomy-The Anatomical Basis of Clinical Practice -41 E (2015)
[PDF] [UnitedVRG] medbooksvn1p\470

39

 14) Moore - Clinically Oriented Anatomy, 7th Edition 2014 p\1018

15) Netter_s Clinical Anatomy, Third Edition- John T. Hansen 2014 p\94

16) Grays Anatomy-The Anatomical Basis of Clinical Practice -41 E (2015)

[PDF] [UnitedVRG] medbooksvn1 p\470

17) Rykova Y, Shuper S, Shcherbakovsky M, Kikinchuk V, Peshenko A.

[MORPHOLOGICAL CHARACTERISTICS OF THE THYROID
GLAND OF MATURE RATS IN MODERATE DEGREE CHRONIC
HYPERTHERMIA]. Georgian Med News. 2019 Jul-Aug;(292-293):75-81.
[PubMed]

18)Jacobsen B, VanKampen N, Ashurst JV. StatPearls [Internet]. StatPearls

Publishing; Treasure Island (FL): Jul 31, 2021. Anatomy, Head and Neck,
Thyrohyoid Membrane.
19) Mescher, Anthony L, and Luis C Junqueira. Junqueira's Basic Histology.
13th ed., New York, Mcgraw-Hill Medical, 2013.
20) Moore - Clinically Oriented Anatomy, 7th Edition 2014 p\1021
21) Grays Anatomy-The Anatomical Basis of Clinical Practice -41 E (2015)
[PDF] [UnitedVRG] medbooksvn1 p\470
22) Moore - Clinically Oriented Anatomy, 7th Edition 2014 p\1020
23)Khakisahneh S, Zhang XY, Nouri Z, Hao SY, Chi QS, Wang DH. Thyroid
hormones mediate metabolic rate and oxidative, anti-oxidative balance at
different temperatures in Mongolian gerbils (Meriones unguiculatus). Comp
Biochem Physiol C Toxicol Pharmacol. 2019 Feb;216:101-109. [PubMed] .

24) Mughal BB, Fini JB, Demeneix BA. Thyroid-disrupting chemicals and
brain development: an update. Endocr Connect. 2018 Apr;7(4):R160-R186.
[PMC free article] [PubMed]

25)Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW,
Spencer CA, Braverman LE. 2002. Serum TSH, T(4), and thyroid antibodies
40

in the United States population (1988 to 1994): National Health and Nutrition
Examination Survey (NHANES III). J Clin Endocrinol Metab 87(2):489–
499.26) Robbins Basic Pathology 10e p/758-760

26) http://www.btf-thyroid.org/information/leaflets/37-psychological-
symptoms-guide

27) Maljaei, MB, Moosavian, SP, Mirmosayyeb, O, Rouhani, MH, Namjoo, I,

Bahreini, A. Effect of celery extract on thyroid function; is herbal therapy safe
in obesity?. Int J Prev Med 2019;10:55. https://doi.org/10.4103/
ijpvm.IJPVM_209_17.

28)Vanderpump MPJ. How should we manage patients with mildly increased

serum thyrotrophin concentrations? Clin Endocrinol 2010;72:436–40.

29)Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders.

Lancet Diabetes Endocrinol. 2015;3:286–95.
CrossRef

30) WHO global database on iodine deficiency. Geneva: World Health

Organisation. http://www.who.int/vmnis/database/iodine/
iodine_data_status_summary/en/index.html. Accessed 6 Nov 2016.
2) Merck Manual Professional Version. https://www.merckmanuals.com/
professional/pediatrics/endocrine-disorders-in-children/hypothyroidism-in-
infants-and-children. Accessed Oct. 10, 2018.

41

42
43
44
45