ENDOCRINE SYSTEM DISORDER

Zar Nigar
Nursing Instructor
CON UCHS
 THE ENDOCRINE SYSTEM
The endocrine system uses chemical substances
as a means of regulating and integrating body
functions. The endocrine system participates in
many essential body functions such as:
• Regulation of digestion
• Uses and storage of nutrients
• Growth and development
• Electrolyte and water metabolism
• Reproduction.
 HORMONES

• Hormones are the chemical messenger that are

transported in body fluids. They are highly specialized
organic molecules produced by endocrine cells that
exert their action on specific target cells.
• The hormone is derived from the Greek word which
means “arouse to activity”.
• Hormones are always present in body fluids all the time
in lesser or greater amounts’
• Hormones are released from various organs some are
released by specialized endocrine glands and some by
organs that have secondary endocrine function.
 HORMONAL ACTIONS

• Hormones are classified as :

• ENDOCRINE : The effect is endocrine when a hormone is release into the
circulation and then travels in the blood to produce a biological effect on
distant target cell.
• PARACRINE : Some hormones and hormones like substances never enter
the bloodstream but instead act locally e.g. action of sex steroids on the
ovaries
• AUTOCRINE : The hormone effect is autocrine when the hormone
produces a biological effect on the same cell that produce it e.g. the
release of insulin from pancreatic beta cells can inhibit the release of
additional insulin from the same target
• INTRACRINE : The final classification of hormone effect intracrine describe
a hormone that is synthesized and act intra cellulary
in the same cell
• NEUROENDOCRINE : Some hormonal effect are neuro endocrine e.g.
vasopressin and epinephrine
 STRUCTUAL CLASSIFICATION

• Hormones are classified into four categories :

• AMINES AND AMINO ACID : Epinephrine and norepinephrine
which are derived from a single amino acid e.g. (tyrosine) and
thyroid hormones which are derived from to iodinated tyrosine
amino acid residue.
• PEPTIDES PROTIENS & GLYCOPROTIENS : Protein based hormone
constitute the majority hormones these protein hormones can be
as small as thyrotropin releasing hormone (TRH) which contains
three amino acids and as large and as complex as growth hormone
(GH) which has approximately 200 amino acids.
• STERIODS :they are derivatives of cholesterol
• FATTY ACIDS : Hormonal messenger molecules are derived from
fatty acids including the group of chemicals called the eicosanoids.
The important among these class are arachidonic acid derivatives
 SYNTHESIS AND RELEASE
The mechanism for hormone synthesis and release vary with
hormone structure.
• Protein hormone: They are synthesized and stored in vesicles in
the cytoplasm of the endocrine cells until secretion is required in
response to some stimuli. The stimulation of cells cause the
vesicles to move to cell membrane and release hormone. The
protein hormone is synthesized in the form of precursor that
requires folding and essential linkage. This is called pro hormone.
• Cholesterol based hormone: They are not stored in vesicles.
They are lipid soluble molecules and are produced in SER. they
leave the cells as they are produced and diffuse across the cell
membrane .it includes glucocorticoids, androgens, estrogens and
mineralocorticoids’ e.g. in adrenal cortex pregnenolone and
other hormones are converted into the aldosterone , cortisol and
androgens enzymatic ally.
 TRANSPORT

• When hormones are released into the bloodstream ,they circulate as free,
unbound or attached to transport carriers.
• Protein hormones are water soluble molecules and do not require a
transport carrier.
• Steroid and thyroid hormones are lipo philic and require a carrier protein.
• The proteins are synthesized in the liver. The extent of protein carrier
influences the rate at which the hormone leave the blood and enter the
cells.
• The half-life of hormone is positively correlated with its percentage of
protein binding; thyroxine has half-life of 6 days while angiotensin II has
less than 1 minute.
• Drugs that compete with a hormone for binding with transport carrier
molecules increase hormone action by increasing the availability of the
active unbound hormone. E.g.: aspirin competes with the thyroid
hormone for binding to transport protein.
 MECHANISM OF ACTION

• Hormones produce their effects through interaction with high affinity receptors
• The rate at which the hormones react depends on their mechanism of action
e.g. Neurotransmitters have reaction time of milliseconds while thyroid
hormone requires days for its full effect to occur.
• RECEPTORS: They are complex structures either located on the cell surface or
inside the target cells. They are specific for each hormone and responds
towards a specific target cells. E.g. : thyroid receptors are specific for TSH.
• The degree of responsiveness depends on number and affinity of the receptor.
• Decrease level of hormone produce increase number of receptors by a process
called up-regulation. This increase the sensitivity of body towards the
hormone.
• Sustained levels of excess hormone often lead to a decrease in receptor
number through a down-regulation.
• The process of up- regulation and down-regulation of receptors is regulated
largely by inducing or repressing the transcription of the genes.
• INTRACELLULAR RECEPTORS:
• Lipid soluble hormones are non polar and can pass freely to the
cell membrane to bind with intracellular receptors. The
intracellular hormone receptor complex can then directly exert
the hormonal effects by entering the cell nucleus to bind with the
hormone response elements that activate or suppress the
intracellular mechanism of protein synthesis.
• CELL SURFACE RECEPTORS:
• Peptide hormone and catecholamine are polar molecules due to
low lipid solubility and high electric charge cannot cross the lipid
cellular membrane the interact with surface receptors to generate
intracellular signal through a second messenger signaling system
with hormone acting as first messenger.e.g.The first messenger
glucagon hormone binds to surface receptors on liver cells to send
a second intracellular message for glycogen breakdown.
 CONTROL OF HORMONE LEVELS

• Hormone secretions varies widely over a 24 hour

period.
• some hormones such growth hormone (GH) and
adreno corticotrophic hormone(ACTH) have diurnal
fluctuation that vary with the sleep and wake cycle.
• The females sex hormones are secreted in a
complicated cyclic manner.
• The levels of hormones such as glucose(insulin) and
water (ADH) in the body.
 HYPOTHALAMIC- PITUITARY REGULATION

• The level of many hormones are regulated by

feedback mechanism that involves the
hypothalamic pituitary target cell system.
• LOCATION OF HYPOTHALAMUS: the hypothalamus
is located centrally in the brain.
Functions:
• It serves as a coordinated center of the brain for
endocrine behavior and autonomic nervous system
function.
• It also controls the level of emotion ,pain ,body
temperature and other neural inputs.
 LOCATION OF PITUITARY GLAND
• The pituitary gland is also called a hypophysis pituitary gland is
connected to the floor of hypothalamus by the pituitary stalk with the
main structural portion of the pituitary gland encased in a bony
structure called sella turcica. It has two sections structurally:
• Anterior pituitary: It is called as adeno hypophysis due to its glandular
structure. The hypothalamus and anterior pituitary are connected by
the blood flow through the hypophysial portal venous system which
begin in the hypothalamus and drain into the anterior pituitary gland.
• Posterior pituitary: It is also known as neuro hypophysis. The
hypothalamus and posterior pituitary are connected by the nerve
axons that originate in the hypothalamus and connect the supr aoptic
and para ventricular nuclei of the hypothalamus with the posterior
pituitary gland.
 HYPOTHALAMIC HORMONES
• The hypothalamic hormone are releasing or inhibiting hormone
based on the response send to the anterior pituitary.
• Releasing hormone: The increase the synthesis and release of
particular hormone
• Inhibiting hormone: They have a reverse effect. they decrease the
hormonal release by the anterior pituitary.
• The hypothalamic hormones that regulate the secretion of the
anterior pituitary hormones
1. GH-releasing hormone(GHRH).
2. Somatostatin.
3. Dopamin
4. TRH
5. Corticotrophin releasing hormone (CRH)
6. Gonadotrophin releasing hormone (GnRH)
• The hypothalamus also send regulatory signals to the posterior
pituitary hormones are ADH and Oxytocin are synthesized in the
cell bodies of the neurons in the hypothalamus that have axons
that travel to the posterior pituitary.
• ACTIVITY OF HYPOTHALAMUS: Neural signals are mediated by
the neurotransmitters such as acetylcholine, dopamin,
nor epinephrine, serotonin , GABA and opoids. It also involves
cytokines that are involved in the immune and inflammatory
responses such as inter leukines which are also involved in
regulation of hypothalamic functions
• PITUITARY HORMONES: Pituitary gland is also called as master
gland. Hormones produced by the anterior pituitary control body
growth and metabolism(GH),function of thyroid gland (TSH),
gluco corticoid hormone level (ACTH), functions of gonads(FSH
and LH)and breast growth and milk production (prolactin)
 FEEDBACK REGULATION

• NEGATIVE FEEDBACK CONTROL : When hormone level rise above

the set point of the system the sensor cause the production and
release of hormone decrease’
• For example: Sensors in the hypothalamus or anterior pituitary
gland detect and increase in thyroid hormone and this causes the
reduction of TSH with a decrease in the output of thyroid hormone
from the thyroid gland.
• POSITIVE FEEDBACK CONTROL : In positive feedback control rising
level of the hormone cause another gland to release a hormone
that is stimulating to the first e.g. Female ovarian hormone estradiol
. increase estradiol production during the follicular stage of
menstrual cycle causes increased gonado trophin (FSH) production
by the anterior pituitary gland. This stimulate further increase
estradiol levels until the dimise of the follicle , which is the source of
estradiol ,result in a fall of gonado trophin levels.
 DISORDER OF ENDOCHRINE CONTROL OF
GROWTH AND METABOLISM
Disturbances of endocrine function usually are
related to either,
• Hypo function
• Hyper function
• Harmon resistance
 ENDOCRINE DISORDERS

• Endocrine disorder can be classified as,

• primary disorder
• secondary disorder
• Tertiary disorder
 PRIMARY DISORDER
Primary disorder because of a dysfunctions of a
target and of the hypothalamic pituitary axis
such as thyroid gland or the adrenal gland.
• Example: total thyroidectomy produce a
primary deficiency of thyroid hormone
ADDISON DISEASE Is another example of
primary endocrine disorder. In addition disease,
the adrenal cortex is damaged by autoimmune
mechanism, resulting in under production of
adrenal cortical hormone.
• SECONDARY DISORDER:
In secondary disorder of endocrine function gland is not
producing appropriate levels of hormone because it is
not receiving appropriate stimulation from the pituitary
gland. The actual source of dysfunction is at the level of
pituitary y gland.
• Example: Pituitary adenoma that results in increased
secretion of pituitary hormones and excessive
stimulation of target endocrine lands such as the adrenal
gland and thyroid gland.
• TERTIARY DISORDER:
Tertiary disorder of endocrine functions , resulting from
defect in the hypothalamus . (May as occur with cranio
pharyngiomas or cerebral irradiation).
 PITUITARY GLAND AND GROWTH DISORDERS
The pituitary gland or hypophysis is a pea sized gland.
Location :It is located in the base of the brain, where it lies in
saddle shaped depression in the sphenoid bone called the sella
turcica. A short funnel shaped stalk the infundibulum connects
the pituitary gland with hypothalamus.
Components :
• There are two components which are as follow:
• Posterior lobe
• It is neural component( neurohypophysis).
• Anterior lobe
• It is glandular lobe ( adenohypophysis). It produce ACTH ( It
control release of cotrisol from adrenal gland) , TSH ( it control
secretion of thyroid hormone from the thyroid gland), GH, FSH
( it regulate fertility in the ovaries and testes), LH ( it regulate sex
 ASSESSMENT OF HYPOTHALAMIC PITUITARY
FUNCTION
• It is done by measuring the following;
• Serum cortisol
• Serum prolactin
• Serum thyroxine and TSH
• Serum testosterone , serum estrogen and serum LH/FSH.
• Serum GH and serum insulin like growth factor -1
• Plasma osmolality and urine osmolality
• The following methods are used;
• Magnetic resonance imagings
• Dynamic testing of hypothalamic pituitary adrenal axis
functioning
• Glucagon stimulation test
 PITUITARY TUMORS

• The pituitary tumors are divided into following;

• Primary tumor
• Secondary tumor
• Functional tumor
• It consist of benign adenomas.
• Nonfunctional tumor
• It consist of small lesion ( micro adenomas <10mm)
to large tumor ( macro adenomas >10mm). it is
found in up to 27% of adults.
 HYPOPITUITARISM
Definition:“ It is characterized by a decrease secretion of pituitary
hormones and is associated with increased morbidity and mortality”
Causes:
• The causes are as follow;
• Tumors and mass lesions
• Pituitary surgery or radiation
• Infiltrative lesion and infections
• Pituitary infarction
• Pituitary apoplexy
• Genetic disease
• Empty sella syndrome
• Hypothalamic disorder
 Signs and symptoms:

These are as follow;

• Weakness
• Fatigue
• Loss of appetite
• Impairment of sexual function
• Cold intolerance
• Nausea
• Anorexia
• Fever
• Postural hypotension
 SEQUENCE OF LOSS OF PITUITARY FUNCTION :

• GH ( Growth hormone)
• LH ( Luteinizing hormone )
• FSH ( Follicle stimulating hormone )
• TSH ( Thyroid stimulating hormone)
• ACTH ( Adeno corticotrophic hormone )
• Treatment:
• It include ;
• Cortisol replacement
• Thyroid replacement
• Sex hormone replacement
• GH replacement
•
 GROWTH HORMONE
Definition:
• It is also known as somato tropin. It is 191 amino acid polypeptide
hormone synthesized and secreted by special cells in the anterior
pituitary called somato tropes.
• Children with diabetes particularly those who have difficulty with
balancing blood sugar often fail to grow normally even through GH
levels are normal.
• Gluco corticoid at excessive level inhibit growth
• Thyroid hormone in less amount result in decreases growth
• Many of the effects of GH depend on IGFs (Insulin like growth
Factors) also called somato medins , produced by liver and four IGFs
have been identified.
• It is carried unbound in plasma.
• Its peak level occurring 1 to 4 hours after onset of sleep.
 Function
• Its functions are as follow;
• It increase growth of visceral, endocrine organs, skeletal muscle ,
cardiac muscle, skin and connective tissue.
• It increase protein synthesis
• It increase fatty acid mobilization
• It increase glucose level
• It increase insulin level
• Its half life is <50 minutes.
• GH secretion is stimulated by; hypoglycemia , fasting, starvation,
increase blood level of amino acids, decreased blood level of fatty
acids, stress, trauma, estrogen, testosterone and ghrelin (Hunger
Hormone produced entero endocrine cells of GIT).
• GH secretion is inhibited by ;increase glucose level, increase level
of fatty acid in blood, cortisol, obesity, aging.
 SHORT STATURE IN CHILDREN

Definition:
• It is a condition in which height is less than the
third percentile on appropriate growth curve
( which is <2 standard deviations below the
population mean for age and sex).
 Causes

• Low birth weight ( intrauterine growth retardation)

• Primary GH deficiency
• Idiopathic GH deficiency
• Pituitary agenesis
• Secondary GH deficiency
• Biologically inactive GH production
• Deficient IGF-1 production
• Hypothyroidism
• Diabetes mellitus
• Glucocorticoid excess
• Endo genous ( cushing syndrome)
• Exo genous ( glucocorticoid drug treatment)
• Abnormal mineral metabolism
• Chronic organic and systematic disease
• Nutritional deprivation
• Mal absorption syndrome
 Diagnostic tests

• Complete blood count

• C-reactive protein test
• Erythrocyte sedimentation rate
• Karyo typing
• Test for IGFBP-3
• Magnetic resonance imaging test
 Forms

• There are two forms of short stature which are genetic ( familial)
and constitutional short stature.
• There height close to the mid parental height of their parents.
• The bone age and chronological age of these children are
equivalent.
• Common technique for estimating a person's bone age is to
compare an x-ray of the patient's left hand and wrist to a
reference atlas containing x-ray images of the left hands of
children considered to be representative of how the skeletal
structure of the hand appears for the average person at a given
age.
• A pediatric radiologist specially trained in estimating bone age
assesses the patient's x-ray for growth, shape, size, and other
bone features.
 Measurement techniques

• Estimating the bone age of a living child is typically

performed by comparing images of their bones to
images of models of the average skeleton for a
given age and sex acquired from healthy children
and compiled in an atlas.
• Features of bone development assessed in
determining bone age include the presence of
bones (have certain bones ossified yet), the size
and shape of bones, the amount of mineralization
(also called ossification), and the degree of fusion
between the epiphyses and meta physes.
 TALL STATURE IN CHILDREN

Definition:
• Height that is greater than the 97th percentile
norms for age and sex is considered tall stature
in children ( >2 standard deviations above the
population mean). It is of 2 types familial and
constitutional tall stature. Its causes are genetic
and chromosomal disorder such as marfan
syndrome, klinefelter syndrome, fragile
syndrome and beckwith wiedemann syndromw.
 GH excess in children & Adults
Gigantism:
• GH excess occurring before puberty and fusion of the
epiphyses of long bones results in pituitary gigantism.
• It is caused by excessive secretion of GH by somatotrope
adenomas causes gigantism, when epiphyses not fused, when
high level of IGF-1 stimulate excessive skeletal growth.
• Its treatment include octreotide and pegvisomant.
Acromegaly :
• When GH excess occur in adulthood or after the epiphyses of
the long bone have fused the condition is referred to as
acromegaly.
• The annual incidence is 3 to 4 cases per 1 million people with
prevalence of 30 to 60 cases per million.
 Etiology and pathogenesis

• It include following;
• GH secreting somato trope adenoma in pituitary
gland
• Hypo thalmic tumor that result in excess secretion of
GHRH
• Ectopic secretion of GHRH by non endocrine tumors
• GH secretion from non endocrine tumors
• The binding of excess circulating GH with GH
receptor in hepatic cells triggers an excess secretion
of IGF-1 from hepatic cells.
 Clinical manifestation:

• Bone of hand, feet, face and skull enlarge

• Broad and bulbous nose/Protruding lower jaw
• Slanting forehead/Teeth splayed
• Difficulty chewing
• Larynx enlarge
• Kyphosis or hunchback
• Heart enlarge/Accelerated atherosclerosis
• Lipolysis/Ketone formation
• sweating /Oily skin/Heat intolerance
• Moderate weight gain
• Muscle weakness/Fatigue
• Menstrual irregularities /Decreased libido
• Sleep apnea
• Colonic polyps /Colorectal cancer
• Diagnosis:
• It include serumIGF-1 test
• Plasma IGF-1
• Glucose challenge test
• Magnetic resonance imaging
• CT scan
• Visual field testing.
• Treatment:
• It include somato statin analog drug peg visomant,
• Dopamine agonist,
• Radiotherapy, removal or reduction of tumor mass,
relieving central pressure effects, normalization of IGF-1
levels to age and sex matched control levels.