Disorders of the Endocrine System

Dr. Mehzabin Ahmed

The major malfunctions/ diseases of the system may be due to:

1.     Hyperfunction of the gland

2.     Hypo function of the gland

3.     Tumor in the glands

 PITUITARY
Hyperfunction: may be due to hyperplasia or a functioning neoplasm 
excessive hormones production  stimulation the target organs 
varied clinical features. For eg.
growth hormone secretion
– in the prepubertal age group results in gigantism and
– in the postpubertal causes acromegaly.
thyrotrophic hormone  increased stimulation of the thyroid gland
 increased thyroid hormone production  hyperthyroidism
characterized by anxiety, increased sweating, tremors and palpitations.
adrenocorticotrophic hormones  Cushing’s disease.
Hypofunction: may be due to destruction of the gland by tumor
infiltration or compression or Ischemic necrosis. The whole or only a
part of the gland may be involved.
• Sheehan syndrome: Post partum hemorrhage  hypotensive shock 
ischemic necrosis of the anterior pituitary  hypofunction 
Simmond’s disease is the effect of this hypofunction  The first
symptom is the failure of lactation due to prolactin deficiency.
Posterior pituitary/ neurohypophysis:
• Diabetes insipidus: Deficiency of ADH due to destruction, tumors or
trauma  production of large volumes of dilute urine (polyuria),
accompanied by polydipsia (excess drinking of water as a
compensation).
 Tumors of the pituitary
Primary tumors of the pituitary are almost always benign and are called
adenomas.
Clinical effects of these adenomas is due to:
1. Excess hormone production: Functional adenomas produce
symptoms depending on the cell type involved.
2. Pressure effects on the surrounding structure like the surrounding
pituitary resulting in hypofunction, on the optic chiasma producing
bitemporal visual field defect.
3. Intracranial space occupying lesion resulting in headaches, nausea,
vomiting.
 Goitre

• It is the term used for enlargement of the thyroid gland. It can be:
• Simple goitre: they are due to hyperplasia, with eventual fibrosis
separating hyperplastic areas from less active areas giving it a
multinodular appearance (Multinodular goitre).
• Colloid goitre: accumulation of large amounts of colloid, it can
even form cysts
 Thyroid gland
Hyperthyroidism
• Due to overproduction of the thyroid hormones T3 and T4 and rarely
due to increased TSH or thyroid stimulating hormone.
• Grave’s Thyroiditis: usually presents as diffuse goitre. It is an example
of an organ specific autoimmune disease. The autoantibody produced
is of the IgG type and is called LATS (long acting thyroid stimulator).
– It binds to the receptor on the follicular cells  stimulates it like
the TSH.
– Features of hyperthyroidism: palpitations, anxiety, increased
sweating and heat intolerance, exophthalmus (eyeballs appear to
pushed out giving a staring look), fingernail clubbing, and pretibial
myxoedema (accumulation of mucopolysaccharides in the deep
dermis of the skin).
• Toxic nodular goitre: Goitre is the enlargement of the thyroid gland
either due to hyperplasia or tumor. A nodular goitre may have one or
two hyperfunctioning nodules
• Functioning adenoma
Hypothyroidism:
A deficient production of the thyroid hormones, due to
• Congenital: it is called Cretinism. It can be due to deficient intake of
iodine as in endemic forms, or due to congenital absence of thyroid
glands or due to enzyme defects blocking the hormone production.
• Aquired : it is called Myxoedema.
– Commonest cause in the adults is the Hashimoto’s Thyroiditis, an
autoimmune disorders resulting in atrophy and fibrosis.
– Surgical removal of the thyroid gland or drugs like sulphonyl ureas,
lithium, resorcinol may cause hypothyroidism.
– Characterized by a decreased metabolic rate (decreased sweating,
weight gain, dry cold skin, cold intolerance, slowing of activity), dry
hair, menstrual irregularities, constipation, accumulation of
mucopolysaccharides (puffy face, thick dry skin, loss of outer third of
the eyebrows), Ischemic heart disease and psychosis.
 Tumors of the thyroid
1.   Benign: they are the follicular adenomas
2.   Malignant: they include carcinoma lymphomas. The carcinomas
can be of four types,
• Papillary adenocarcinoma (often multifocal & spread lymphatically),
• Follicular adenocarcinoma (usually solitary & spreads by blood),
• Medullary carcinoma (arises from the C- cells or the calcitonin
producing cells) and
• Anaplastic (high grade tumor with a very poor prognosis
• The lymphomas are the Non Hodgkin's lymphoma of the B cell type.
 Parathyroid glands
Hyperparathyroidism: secretion of parathyroid hormone due to:
• Primary: due to hyperplasia or adenoma. It is seen usually in the
postmenopausal females and present clinically as renal stones, muscle
weakness, tiredness, thirst and polyuria, anorexia and constipation,
and rarely with peptic ulcers (increased gastrin secretion)
• In the bones it causes osteitis fibrosa cystica, also called
vonRecklinghausen’s disease or the brown tumors. It results from
increased bone resorption by the osteoclasts first seen in the phalanges.
As the disease progresses cystic lesions form into which hemorrhage
may occur, thus called brown tumors though they are not tumors.
• Secondary: hyperparathyroidism in response to prolonged
hypocalcemia
• Tertiary: development of a parathyroid adenoma in a long standing
cases of secondary hyperparathyroidism
• Hyperparathyroidism is an important cause of hypercalcemia
(increased calcium levels in the blood). Other causes include
– disseminated malignancies in the bones,
– vitamin D intoxication,
– milk-alkali syndrome,
– Sarcoidosis and
– multiple myeloma.
• Hypoparathyroidism  fall in the calcium levels of the blood. It may
be due to removal or damage to the parathyroids, idiopathic or
congenital deficiency. It results in tetany (spasm of the skeletal
muscles), convulsions, parasthesia, psychiatric disorders, and rarely
cataracts and brittle nails.
 Adrenal glands
Glucocorticoids:
• Cushing syndrome is caused by the excess secretion of
glucocorticoids, either due to hyperplasia or adenoma in the adrenal
cortex.
• Cushing’s disease are the features produced due to increased
secretion of the ACTH by the pituitary resulting in the increased
production of the glucocorticoids.
• Clinical features: these patients present as
– obese individuals with central or truncal obesity (buffalo hump),
– moon facies, abdominal striae
– hypertension,,
– impaired wound healing, immunosuppresed (infections are
therefore common),
– osteoporosis and fractures,
– proximal muscle weakness,
– peptic ulcers in the stomach, renal stones,
– cataracts,
– menstrual disturbances, and diabetes mellitus.
• Acute hyposecretion is seen in acute hemorrhagic necrosis of the
adrenals. It is called Waterhouse Frederichsen syndrome.
• Chronic insufficiency is called Addison’s disease. It may be caused
by tuberculosis of the adrenals, autoimmune destruction,
Amyloidosis, hemochromatosis, metastatic tumors or due to atrophy
due to prolonged steroid therapy.
The clinical presentation is
– anorexia, weight loss, vomitting, weakness, lethargy,
– hypotension,
– skin pigmentation,
– hyponatremia (low sodium) with hyperkalemia (increased
potassium) and
– sexual dysfunction.
Mineralocorticoids:
Aldosterone that functions in the reabsorption of sodium and chloride
and thus the water also. It thus helps in the maintainence of the
plasma volume.
• Conn’s syndrome is hyperaldosteronism results from increased
production of aldosterone. The resulting renal retention of sodium and
the loss of potassium cause muscle weakness, cardiac arrhythmias,
tetany and parasthesias.
Sex steroids:
Androgens are synthesized though to a lesser degree. Excess
production causes virilization of the female.
 Adrenal medulla

• It synthesizes catecholamines, which maintain the blood

pressure by vasoconstriction of the blood vessels in the skin, gut
and skeletal muscles. Hypersecretion may be due to
phaeochromocytoma or a tumor growth in the adrenal
medulla.
• Clinical features include
– hypertension (rapid progress especially in the young
patients),
– pallor,
– headaches, excessive sweating and
– nervousness
 Endocrine Pancreas-
Diabetes mellitus
• Abnormal metabolic state characterized by glucose intolerance due to
inadequate insulin action. As the actions of insulin are anabolic (laying
down of tissue stores from circulating nutrients) , its deficiency
therefore promotes catabolism (breakdown of tissue energy stores).
• Thus the major features of DM are:
• Overproduction and inability to utilize glucose resulting in
hyperglycemia
• Decreased protein synthesis thus there is rapid weight loss and
wasting
• Lipolysis resulting in hyperlipidemia
 Clinical features
• The hyperglycemia exceeds the renal threshold for glucose
reabsorption and the excess is therefore excreted in the urine-
glycosuria.
• Water is therefore compulsorily lost along with the glucose- osmotic
diuresis. This causes polyuria (increased excretion of urine),
dehydration and polydypsia (increased thirst and water consumption).
• Lipolysis results in production of free fatty acids from the breakdown
of the fat stores. This is converted into ketone bodies by the liver and
results in metabolic acidosis- diabetic ketoacidosis.
• Severe ketosis (increased circulating ketonebodies in the blood),
acidosis, hyperosmolarity (due to increased glucose in the blood) and
electrolyte disturbances results in impaired cerebral function- diabetic
ketoacidotic coma.
• Insulin overdosage in a diabetic patient causes hypoglycemic coma (the
circulating glucose levels are decreased).
 Classification
• Type I: also called insulin dependent diabetes mellitus
(previously called juvenile onset DM) – accounts for 10% of the
cases.
• Type II: also called noninsulin dependent DM (previously
called adult onset DM) – accounts for the remaining 80 – 90% of
the cases.
• MODY – maturity onset diabetes of the young: results from
genetic defects of β cells function (Autosomal dominant
transmission) – accounts for less than 5% of the cases
manifesting as mild hyperglycemia.
• Environmental agents may play a role in the pathogenesis of
type I DM. The agents implicated are the viruses like coxsackie
viruses, mumps, measles, cytomegalovirus, rubella and
Ebstein-Barr virus. These viruses trigger an autoimmune
reaction in the islet cells by expression of sequestered (hidden)
antigens or by molecular mimicry.
• Cow’s milk ingestion early in life, chemical toxins like
streptozocin, pentamidine etc. are also said to play a role in
antibody production that may destroy the pancreatic islet cells.

• Diabetes of both types results in the same complications,

mediated by an identical damage to the large and the small
vessels, the peripheral nerves and the effect on the immune
system
 Complications
• Large blood vessels: Accelerated atheroma formation leading to
– Myocardial infarction - Cerebrovascular disease
– Ischemic limbs - 80% of adult diabetic deaths
• Small blood vessels: Damage to the endothelial cells and the basal
lamina causing (diabetic microangiopathy)
– Retinopathy resulting in blindness
– Nephropathy due to involvement of kidney (Kimmelstiel Wilson disease)
• Peripheral nerve: Neuropathy- possibly due to involvement of the
small vessels supplying the nerves
• Neutrophils: Increased susceptibility to infection
• Skin: Necrobiosis lipoidica diabeticorum and gangrene of the
extremities
• In pregnancy
– Pre-eclamptic toxaemia
– Large babies
– Neonatal hypoglycemia
 Secondary diabetes
Hypersecretion of any of the five hormones, which exert a hyperglycemic
effect may result in glucose intolerance. Thus
• Cushing’s syndrome – tumor/ hyperplasia of the adrenal cortex
causing hypersecretion of glucocoticoids
• Phaechromocytoma – tumor of the adrenal medulla secreting
adrenaline and noradrenaline in excess
• Acromegaly – tumor/ hyperplasia of the pituitary causing growth
hormone hypersecretion in adults
• Glucagonomas – tumors of the α cells of the islets causes glucagons
hypersecretion
Generalized destruction of the pancreas by an acute or chronic
pancreatitis, hemochromatosis or occasionally carcinoma may result in
insulin deficiency.
 Tumors

• Adenomas and carcinomas of the islets are quite rare. They

present with widespread symptoms produced by the
hypersecretiion of the normal hormones. Eg:
• Insulinomas: insulin,
• Glucagonomas,
• Stomatostatinomas
• Gastrinomas ( gastrin gastricacid causing peptic ulcers-
Zollinger Ellison syndrome)
 Points to remember
• Disease of one gland affects functions of other glands because the
glands are interdependent
• Each hormone has diverse effects, thus malfunctions may produce
numerous clinical features
• Tumors or hyperfunction of one gland may be associated with similar
lesions in other glands as in MEN (multiple endocrine disorders),
involving glands like pituitary, parathyroids and pancreas (MEN-I)
and thyroid, parathyroid, adrenals, GI neuromas (MEN-II)
• Autoimmune disorders involving one gland may affect other glands in
a similar fashion.
• Ectopic production of hormones by non- endocrinal tumors produce
effects like the primary endocrinal disease- these are called
paraneoplastic disorders.