Hyperfunction of posterior pituitary and hypothalamus

These lesions are uncommon and are characterized inappropriate release of ADH and precocious puberty.

1. Inappropriate release of ADH. Inappropriate release of ADH occurs most often in paraneoplastic syndrome. Sometimes, lesions of the hypothalamus such as trauma, haemorrhage and meningitis, pulmonary diseases such as tuberculosis, lung abscess, pneumoconiosis, empyema and pneumonia may cause overproduction of ADH. Excessive release of ADH manifests clinically by passage of concentrated urine due to increased reabsorption of water and loss of sodium in the urine, consequent hyponatraemia, haemodilution and expansion of ultra- and extracellular fluid volume. 

2. Precocious puberty. A tumor  in the region of hypothalamus or the pineal gland may result in premature release of gonadotropins causing the onset of pubertal changes prior to the age of 9 years. The features include premature development of genitalia both in the male and in the female, growth of pubic hair and axillary hair. In the female, there is breast growth and onset of menstruation.

 

Pathology of the adrenal glands

Adrenocortical hyperfunction

There are clinical syndromes: 1) Cushing's syndrome, 2) Conn's syndrome, 3) adrenogenital syndrome.

Cushing's syndrome. excesive production of cortisol by the adrenal gland (primary form).

 This group of cases is characterized by low serum ACTH levels.

 Clinical features:

1. Central or truncal obesity contrasted with relatively thin arms and legs, buffalo hump and rounded oedematous moon-face.

2. Increased protein breakdown resulting in wasting and thinning of the skeletal muscles, atrophy of the skin and subcutaneous tissue with formation of purple striae on the abdominal wall, osteoporosis and easy bruisability of the skin to minor trauma.

3. Systemic hypertension is present in 80% of cases because of retention of sodium and water.

4. Impaired glucose tolerance and diabetes mellitus are found in about 20% cases.

5. Amenorrhoea, hirsutism and infertility in many women.

6. Insomnia, depression, confusion and psychosis.

Conn's syndrome (primary hyperaldosteronism)

This is syndrome occurring due to overproduction of aldosterone with resultant suppression of the renin-angiotensin system and decreased plasma renin activity. Primary hyperaldosteronism is caused by adrenocortical adenoma (80%) and adrenal hyperplasia, especially in children. Clinical features:

1. Diastolic hypertension.

2. Hypokalaemia and associated muscular weakness, peripheral neuropathy and cardiac arrhythmias.

3. Retention of sodium and water.

4. Polyuria and polydipsia due to reduced concentrating power of the renal tubules.

       Secondary hyperaldosteronism, on the contrary, occurs in response to high plasma renin level due to overproduction of renin by the kidneys such as in renal ischaemia, reninoma or oedema. It characteristics are congestive heart failure, decreased renal perfusion, and hypoalbuminemia.

Adrenogenital syndrome (adrenal virilism)

Hypersecretion of sex steroids, mainly androgens, may occur in children or in adults.

1. In children, it is due to congenital adrenal hyperplasia in which there is congenital deficiency of a specific enzyme.

2. In adults, it is caused by an adrenocortical adenoma or a carcinoma. Cushing's syndrome is often present.

The clinical features depend upon the age and sex of the patient.

1. In children, there is distortion of the external genitalia in girls, and precocious puberty in boys.

2. In adults, the features in females show virilisation (e.g. hirsutism, oligomenorrhoea, deepening of voice, hypertrophy of the clitoris); and in males may rarely cause feminisation.

3. There is generally increased excretion of 17-keto-steroids in the urine.

Adrenocortical insufficiency (hypoadrenalism)

Three types of adrenocortical hypofunction are distinguished:

1. Primary adrenocortical insufficiency caused primarily by the disease of the adrenal glands. Two forms are described: 1) acute or «adrenal crisis», and 2) chronic or «Addison's disease».

2. Secondary adrenocortical insufficiency resulting from diminished secretion of ACTH.

3. Hypoaldosteronism characterised by deficient secretion of aldosterone.

Primary acute adrenocortical insufficiency (adrenal crisis)

Sudden loss of adrenocortical function may result in an acute condition called adrenal crisis.

Etiopathogenesis. Causes of acute insufficiency are:

1. Bilateral adrenalectomy.

2. Septicaemia e.g. in endotoxic shock and meningococcal infection. 

3. Rapid withdrawal of steroids.

4. Any form of acute stress in a case of chronic insufficiency i.e. in Addison's disease.

Clinical features.

1. Deficiency of mineralocorticoids (i.e. aldosterone deficiency) results in salt deficiency, hyperkalaemia and dehydration.

2. Cortisol deficiency leads to hypoglycaemia, increased insulin sensitivity and vomiting.         

Primary chronic adrenocortical insufficiency (Addison's disease)

Progressive chronic destruction of more than 90% of adrenal cortex on both sides results in an uncommon clinical condition called Addison's disease.

Causes: tuberculosis, autoimmune or idiopathic adrenalitis, histoplasmosis, amyloidosis, metastatic cancer, sarcoidosis.

Clinical Features. Clinical manifestations develop slowly.

1. Asthenia i.e. progressive weakness, weight loss and lethargy as the cardinal symptoms.

2. Hyperpigmentation,

3. Arterial hypotension.

4. Loss of appetite, nausea, vomiting and upper abdominal pain.

5. Lack of androgen causing loss of hair in women.

6. Episodes of hypoglycaemia.

7. Biochemical changes include reduced GFR, acidosis, hyperkalaemia and low levels of serum sodium, chloride and bicarbonate. Plasma ATCH level is elevated.