Download The endocrine system

Khairat Battah, MD
The University of Jordan
Faculty of medicine, pathology department
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Divided into :
Anterior pituitary.
Posterior pituitary.
Diseases include:
Hyperpituitarism.
Hypopituitarism.
Local mass effect.
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The most common cause of hyperpituitarism is a pituitary
adenoma arising in the anterior lobe.
Pituitary adenomas are classified on the basis of hormone(s)
produced by the neoplastic cells.
Functional and non-functional adenomas usually composed
of a single cell type.
Nonfunctioning and hormone-negative adenomas are likely
to come to clinical attention at a later stage and are,
therefore, more likely to be macroadenomas than are lesions
associated with endocrine abnormalities.
Pituitary adenomas can be macroadenomas (>1 cm) or
microadenomas (<1 cm).
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Are the most common type of hyperfunctioning
adenoma.
Hyperprolactinemia causes: amenorrhea, galactorrhea,
loss of libido, and infertility.
Hyperprolactinemia may be caused by other conditions
or factors including pregnancy, high-dose estrogen
therapy, renal failure, hypothyroidism, hypothalamic
lesions, and dopamine-inhibiting drugs (e.g., reserpine)
Second most common type of functional pituitary adenoma.
1. If it occurs in prepubertal children, excessive growth hormone
result in gigantism . Is characterized by a generalized increase in
body size, with disproportionately long arms and legs
2. If elevated levels present after closure of the epiphyses,
individuals develop acromegaly:
a. Growth is most conspicuous in soft tissues, skin, and viscera.
b. Jaw enlargement results in its protrusion and separation of the
teeth.
c. The hands and feet are enlarged, with broad sausage-like fingers.
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Growth hormone excess also is associated
with a number of other disturbances
including:
abnormal glucose tolerance and diabetes
mellitus
Generalized muscle weakness
Hypertension
Arthritis, osteoporosis
Congestive heart failure
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Causes hypercortisolism because of the stimulatory
effect of ACTH on the adrenal cortex (Cushing
syndrome) and this is called Cushing disease
Produces two hormones: oxytocin and ADH.
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ADH ( Antidiutitic hormone) acts on the collecting tubules of the
kidney to promote the resorption of free water
Syndromes of ADH excess and defficiency.
1. ADH deficiency causes diabetes insipidus, characterized by
excessive urination (polyuria), polydipsia and increased serum
sodium and osmolality.
It results from head trauma, neoplasms, and inflammatory
conditions of hypothalamus and posterior pituitary or it may be
idiopathic.
2.Syndrome of inappropriate ADH (SIADH) secretion, causes
resorption of excessive amounts of free water, with resultant
hyponatremia, cerebral adema and neurologic dysfunction.
 Oxytocin
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stimulates the contraction of
smooth muscle in the pregnant uterus and of
muscle surrounding the lactiferous ducts of
the mammary glands
Impairment of oxytocin synthesis and release
has not been associated with significant
clinical abnormalities
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Diseases of the thyroid are divided into:
1- Hyperthyroidism and thyrotoxicosis..
2- Hypothyroidism.
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Thyrotoxicosis is a hypermetabolic state due to
elevated circulating levels of free T3 and T4.
I. Associated with hyperthyroidism (Thyroid hyperfunction):
1. Primary:
a. Graves disease.
b. Hyperfunctioning thyroid adenoma.
2. Secondary:
TSH-secreting pituitary adenoma (rare)
II. Not associated with hyperthyroidism
Such as in thyroiditis.
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Constitutional symptoms: Skin is soft, warm, and
flushed; heat intolerance and excessive sweating are
common.Weight loss despite increased appetite.
Gastrointestinal: Stimulation of the gut results in
hypermotility, malabsorption, and diarrhea.
Cardiac: Palpitations and tachycardia are common.
Neuromuscular: nervousness, tremor, and irritability and
muscle weakness (thyroid myopathy).
Ocular manifestations: a wide, staring gaze and lid lag are
present because of sympathetic overstimulation of the
levator palpebrae superioris . However, true thyroid
ophthalmopathy associated with proptosis is a feature
seen only in Graves disease.
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The diagnosis of hyperthyroidism is based on clinical
features and laboratory data.
The measurement of serum TSH is the most useful
single screening test for hyperthyroidism, because TSH
levels are decreased even at the earliest stages, when
the disease may still be subclinical.
In rare cases of pituitary- or hypothalamus-associated
(secondary) hyperthyroidism, TSH levels are either
normal or raised
Causes :
1. Worldwide, the most common cause is dietary
deficiency of iodine.
2. In developed nations – autoimmune Hashimoto
thyroiditis.
3. Genetic defects such as thyroid dysgenesis or
dyshormogentic goiter are rare.
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Cretinism : Hypothyroidism developing in infancy
or early childhood.
Endemic cretinism: common in areas of the
world where dietary iodine deficiency is
endemic,
- Sporadic cretinism: enzyme defects that
interfere with thyroid hormone synthesis
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Clinical features of cretinism
Impaired development of the skeletal system and
central nervous system, with severe mental retardation,
short stature, coarse facial features, a protruding
tongue, and umbilical hernia.
The severity of the mental impairment in cretinism
seems to be directly influenced by the timing of onset
of the deficient state in utero
Myxedema : Hypothyroidism developing in older children and
adults and its manifesations:
 Generalized apathy and mental sluggishness, may mimic
depression.
 Cold intolerant.
 Obesity.
 Mucopolysaccharide-rich edematous fluid accumulates in
skin, subcutaneous tissue, and a number of visceral sites, with
resultant broadening and coarsening of facial features,
enlargement of the tongue, and deepening of the voice.
 Bowel motility is decreased, resulting in constipation.
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Measurement of serum TSH is the most sensitive
screening test for hypothyroidism.
The serum TSH is increased in primary
hypothyroidism because of a loss of feedback
inhibition of thyrotropin-releasing hormone
(TRH) and TSH production by the hypothalamus
and pituitary, respectively.
The TSH concentration is not increased in
persons with hypothyroidism caused by primary
hypothalamic or pituitary disease
Serum T4 is decreased in patients with
hypothyroidism of any origin.
A. Chronic lymphocytic (Hashimoto) thyroiditis :
 Is the most common cause of hypothyroidism in areas
where iodine is sufficient.
 Gradual thyroid failure secondary to autoimmune
destruction of the thyroid gland.
 More common in women
 Presents as diffuse symmetric painless enlargement of the
thyroid, usually associated with some degree of
hypothyroidism.
 In the usual clinical course, hypothyroidism develops
gradually. However, it may be preceded by transient
thyrotoxicosis in some cases.
B. Subacute granulomatous thyroiditis
- Caused by a viral infection and patients have history of
upper respiratory tract infection.
- Acute onset with pain in the neck, fever, and variable
enlargement of the thyroid.
- Transient hyperthyroidism may occur, as result of
disruption of thyroid follicle and release of excessive
thyroid hormone.
- The condition typically is self-limited.
C. Riedel thyroiditis:
- A rare disorder of unknown etiology and characterized
by extensive fibrosis involving the thyroid gland and
adjacent neck structures
- Clinical evaluation demonstrates the presence of a hard
and fixed mass clinically simulates a thyroid neoplasm.
The most common cause of endogenous hyperthyroidism.
It is characterized by a triad of manifestations:
• Thyrotoxicosis, caused by a diffusely enlarged, hyperfunctional
thyroid, is present in all cases.
• An infiltrative ophthalmopathy with resultant exophthalmos is
noted in as many as 40% of patients.
• A localized, infiltrative dermopathy (sometimes designated
pretibial myxedema) is seen in a minority of cases. most
commonly involves the skin overlying the shins.
 Women affected up to seven times more commonly than men
peak incidence between the ages of 20 and 40
 Laboratory findings include elevated serum free T4 and T3 and
depressed serum TSH
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- Goiter is the most common manifestation of thyroid disease and
most often caused by dietary iodine deficiency
- Impaired thyroid hormone synthesis leads to compensatory rise
in the serum TSH, which in turn lead to gross enlargement of
the thyroid gland
- The compensatory increase in functional mass of the gland is
able to overcome the hormone deficiency, ensuring an
euthyroid metabolic state.
1. Endemic goiter: occurs in iodine deficient areas
2. Sporadic goiter: less common than endemic goiter, more
common in females, with a peak in puberty or young adult
life and can be caused by several conditions that interfere
with thyroid hormone synthesis such as: excessive calcium
and certain vegetables (cabbage, cauliflower) and
enzymatic defects.
A-Primary hyperparathyroidism:- Causes
1. Parathyroid adenoma----75%-80%
2. Primary hyperplasia ----10-15%
3. Parathyroid carcinoma---- rare
- The most common manifestation is an increase in serum
calcium.
- Characterized by painful bones, renal stones, abdominal
groans, and psychotic moans.
- Bone pain secondary to fractures of bone (osteoperosis)
- Gastrointestinal tract disturbances: including constipation,
nausea, peptic ulcer, pancreatitis and gallstones
B. Secondary hyperparathyroidism
 The most common cause is chronic renal failure and
the mechanisms:
1. Chronic renal insufficiency causes
hyperphosphatemia. and the elevated phosphate levels
depress serum calcium so stimulate parathyroid
gland activity.
2. loss of renal substances reduces α1-hydroxylase
enzyme which is necessary for the synthesis of the
active vitamin D, which in turn reduces intestinal
absorption of calcium.
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In a minority of patients, parathyroid activity may
become autonomous and excessive, with resultant
hypercalcemia—a process sometimes termed tertiary
hyperparathyroidism.
Parathyroidectomy may be necessary to control the
hyperparathyroidism in such patients.
C- Hypoparathyroidism: causes.
1. Surgical removal of parathyroids during thyriodectomy.
2. Congenital absence: in DiGeorge syndrome.
3. Autoimmune hypoparathyroidism.
The clinical manifestations are secondary to
hypocalcemia and include:
a. Increased neuromuscular irritability including muscle
spasm and tingling.
b. Cardiac arrythmias .
c. Increased intracranial pressures and seizures
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The adrenal glands are paired endocrine organs
consisting of two regions, the cortex and medulla
The adrenal cortex synthesizes three different types of
steroids:
o Glucocorticoids (principally cortisol), which are synthesized
primarily in the zona fasciculata, with a small contribution from
the zona reticularis
o Mineralocorticoids, the most important being aldosterone, which
are generated in the zona glomerulosa
o Sex steroids (estrogens and androgens), which are produced
largely in the zona reticularis
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The adrenal medulla is composed of chromaffin cells,
which synthesize and secrete catecholamines, mainly
epinephrine
1. Hypercortisolism---Cushing syndrome
- In clinical practice, most cases are caused by the administration of
exogenous glucocorticoids.
- The remaining cases are endogenous
A. ACTH-secreting- pituitary adenoma known as Cushing disease
accounts for more than half of the cases of endogenous Cushing
syndrome.
B. Adrenal adenoma and carcinoma and hyperplasia are
responsible for about 20% of cases of endogenous Cushing
syndrome . This form of Cushing syndrome is called ACTHindependent Cushing syndrome.
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Hypertension
Weight gain with truncal obesity and moon facies .
Decreased muscle mass and proximal limb weakness
Glucocorticoids induce gluconeogenesis and inhibit the
uptake of glucose by cells resulting in hyperglycemia,
glucosuria and polydipsia mimicking diabetes mellitus.
Glucocorticoids suppress the immune response so
patients are at high risk of infection.
Hirsuitism and menstrual cycle abnormalities.
Mental disturbances, including mood swings, depression,
and frank psychosis.
2. Hyperaldosteronism:
- Excessive levels of aldosterone cause sodium retention and potassium
execretion, with resultant hypertension and hypokalemia.
- Can be primary or secondary.
1. In secondary type, aldosterone release occurs in response to
activation of the renin-angiotensin system.
- It is characterized by high levels of plasma renin and is caused by:
a. Decreased renal perfusions. (renal artery stenosis)
b. Arterial hypovolemia .(cirrhosis, nephrotic syndrome)
2. Primary hyperaldosteronism:
Indicates a primary autonomous overproduction of aldosterone.
 The potential causes of primary
hyperaldosteronism are:
 Bilateral idiopathic hyperaldosteronism.
 Adrenocortical neoplasm, either an aldosteroneproducing adenoma (the most common cause) or,
rarely, an adrenocortical carcinoma
 Genetic defect that leads to overactivity of
the aldosterone synthase gene
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The clinical hallmark of hyperaldosteronism is
hypertension
The long-term effects of hyperaldosteronism-induced
hypertension are cardiovascular compromise
Hypokalemia results from renal potassium wasting and,
when present, can cause a variety of neuromuscular
manifestations, including weakness, paresthesias,
visual disturbances, and occasionally frank tetany
I-Acute Adrenocortical Insufficiency :
Occurs most commonly in the following clinical settings:
a. Crisis in patients with chronic adreno-cortical insufficiency
precipitated by stress.
b. Rapid withdrawal of exogenous steroid.
c. Massive adrenal haemorrhage that may destroy the adrenal cortex
sufficiently to cause adrenocortical insufficiency.
- This hemorrhage may occur :
1. In patients maintained on anticoagulant therapy.
2. Overwhelming sepsis (Waterhouse-friderichsen syndrome)
associated with Neisseria meningitidis septicemia.
2. Primary Chronic Adrenocortical Insufficiency (Addison Disease)
- More than 90% of all cases are caused by
a. Autoimmune adrenalitis :
Accounts for 60% to 70% of cases and is the most common cause of
primary adrenal insufficiency in developed countries.
b. Infections : mainly tuberculosis.
c. Metastatic neoplasms involving the adrenal mainly carcinomas of
the lung.
3. Secondary Adrenocortical Insufficiency :
Caused by any disorder of the hypothalamus and
pituitary that reduces the output of ACTH leads to
a syndrome of hypoadrenalism having many
similarities to Addison disease such as:
a. Metastatic cancer
b. Infection
c. Infarction
d. Irradiation
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When 90% of the adrenal cortex has been compromised.
a. Progressive weakness and easy fatigability,
b. Anorexia, vomiting, weight loss, diarrhea.
c. Potassium retention and sodium loss, with hyperkalemia,
hyponatremia, volume depletion, and hypotension; due to
decreased aldosterone in primary adrenal insufficiency .
d. In individuals with primary adrenal insufficiency increased
levels of ACTH precursor hormone stimulate melanocytes,
with resultant hyperpigmentation of the skin
by contrast hyperpigmentation is not seen in individuals
with secondary adrenocortical insufficiency (no ACTH).
Diagnosis
Blood glucose levels normally are maintained in a very narrow range,
usually 70 to 120 mg/dL.
The diagnosis of diabetes is established by elevation of blood
glucose:
1. A random blood glucose of 200 mg/dL or higher, with classical
signs and symptoms
2.A fasting glucose concentration of 126 mg /dL or higher on more
than one occasion.
3. An abnormal oral glucose tolerance test (OGTT), in which the
glucose levels is 200 mg/dL or higher 2 hours after a carbohydrate
load (75 g of glucose).
Persons with serum fasting glucose values < 110
mg/dL, or < 140 mg/dL for an OGTT, are considered
euglycemic.
Patients with prediabetes:
- Fasting glucose > 110 but < 126 mg/dL, or OGTT
values of >140 but < 200 mg/dL
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It accounts for 10% of all cases
- It is an autoimmune disease destructing pancreatic B-cells
leading to deficiency of insulin.
- Most commonly develops in childhood, becomes manifest at
puberty, and most patients depend on exogenous insulin for
survival; without insulin they develop serious metabolic
complications.
- The classic manifestations of the disease occur after 90% of
the beta cells have been destroyed.
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- Account for 80% to 90% of DM caused by peripheral resistance to insulin
action .
It is complex multifactorial disease and pathogenesis involves:
I. Environmental factors, such as a sedentary life style and dietary habits.
II. Genetic factors.
Insulin resistance : Defined as the failure of target tissues to respond
normally to insulin and leads to decreased uptake of glucose in
muscle,and inability to suppress hepatic gluconeogenesis.
Metabolic syndrome has been applied to a constellation of findings
dominated by visceral obesity, which is accompanied by insulin
resistance, glucose intolerance, and cardiovascular risk factors
such as hypertension and abnormal lipid profiles
The first 1 or 2 years of diabetes type 1(referred to as the
"honeymoon period"), in which exogenous insulin
requirements may be minimal because of residual
ongoing endogenous insulin secretion but then the beta
cell reserve is exhausted and insulin requirements
increase.
- The onset of the diseases is marked by polyuria,
polydipsia, polyphagia.
-The hyperglycemia exceeds the renal threshold for
reabsorption, and glycosuria induces an osmotic
diuresis and polyuria.
-The obligatory renal water loss combined with the
hyperosmolarity tends to deplete intracellular water,
trigger the thirst centers of the brain leading to
(polydipsia).
- Deficiency of insulin leads to catabolism of proteins
and fats leading to polyphagia.
- Deviations from normal diet, unusual physical activity, infection, or
stress may predispose to diabetic ketoacidosis.
- The plasma glucose is about 500 to 700 mg/dL due to absolute
insulin deficiency and effects of glucagon.
- The marked hyperglycemia causes an osmotic diuresis and
dehydration.
- Insulin deficiency leads to activation of lipoprotein lipase, with
resultant excessive breakdown of dipose stores, giving rise to
increased FAs, which are oxidized by the liver to produce ketones
(ketonemia and ketonuria).
- Accumulating ketones decrease blood pH, resulting in metabolic
ketoacidosis.
- Also may manifest with polyuria and polydipsia, but in
obese patients older than 40.
- Unfortunately, with the increase in sedentary life in
Western society, type 2 diabetes is now seen in
children.
- In some cases, medical attention is sought due to
unexplained weakness.
- Most frequently, however, the diagnosis is made after
routine blood or urine testing in asymptomatic
persons.
In the decompensated state, patients develop hyperosmolar
nonketotic coma.
This syndrome is due to severe dehydration resulting from sustained
osmotic diuresis and urinary fluid loss.
The affected person is an elderly diabetic who is disabled by stroke or
infection and unable to maintain adequate water intake.
 The absence of ketoacidosis and its symptoms (nausea, vomiting,
respiratory difficulties) delays recognition of the seriousness of the
situation until the onset of severe dehydration and coma.
I. Macrovascular Disease mainly accelerated
atherosclerosis
a- Myocardial infarction( MI,) caused by Coronary artery
athero-sclerosis is the most common cause of death in
diabetics.
b- Gangrene of the lower extremities, is 100 times more
common in persons with diabetes than in the general
population.
II. Diabetic Microangiopathy:
- Diffuse thickening of basement membranes, is evident in the
capillaries of the skin, retina and renal glomeruli.
- Diabetic capillaries are more leaky than normal to plasma
proteins.
- The microangiopathy underlies the development of diabetic
nephropathy, retinopathy, and neuropathy.
III. Diabetic Nephropathy: Renal failure is second to MI as a cause
of death from this disease.
- The earliest manifestation of diabetic nephropathy is the appearance
of microalbuminuria (loss of more than 30mg but less than 300 mg
of albumin/day).
- Over the succeeding 10 to 15 years, without specific interventions,
about 80% of patients with type 1 diabetes and 40% with type 2
diabetes will develop overt nephropathy with macroalbuminuria
IV. Ocular Complications:
Visual impairment, is one of the feared consequences of long-standing DM.
Retinopathy, the most common pattern.
1. Nonproliferative retinopathy includes:
a. Intraretinal or preretinal hemorrhages, :
b. (microinfarcts) or“. Microaneurysms (dilations of retinal capillaries)
2. Proliferative type is characterized by many blood vessels in the retina with
fibrosis can lead to blindness.
V. Diabetic Neuropathy.
1- The most frequent is peripheral , symmetric neuropathy of the
lower extremities affecting motor and sensory nerves, particularly the
latter.
2- Autonomic neuropathy, which produces disturbances in bowel
and bladder function and impotence.
- In a person with neuropathy, a trivial infection in a toe may be the
first event in a long succession of complications (gangrene,
bacteremia, pneumonia).
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Several studies have demonstrated that morbidity and
mortality , from diabetes are attenuated by strict glycemic
control.
For patients with type 1 diabetes, insulin replacement
therapy is the mainstay of treatment,
Dietary restrictions and exercise (that improves insulin
sensitivity) are the "first line of defense" for type 2
diabetes.
Most patients with type 2 diabetes will eventually require
therapeutic intervention achieved by administration of a
number of agents that lower glucose levels.
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Glycemic control is assessed by measuring the percentage of
glycosylated hemoglobin (HbA1C ) which is a measure of
glycemic control over long periods of time (2 to 3 months)
and is relatively unaffected by day-to-day Variations.
A HbA1C value below 7% is taken as evidence of tight
glycemic control, but patients with HbA1C levels in this range
also have an increased risk of episodes of therapy-related
hypoglycemia.