Give the causes and consequences of :

(A) DIABETES INSIPIDUS:

Causes: 

The control of Arginine Vasopressin (AVP) release and regulation of fluid balance occurs primarily in response to alterations in blood toxicity and blood volume so that a relative constancy of these two parameters is maintained.

Impairment of neurohypophysial system to synthesize or release AVP results in pituitary (neurogenic) diabetes insipidus. Failure to synthesize AVP can also occur as a result of disease processes that destroy hypothalamus or posterior pituitary. It can also result from traumatic or surgical injury to hypothalamus.

In nephrogenic (AVP resistant ) diabetes insipidus (NDI), there is defect in urinary concentration mechanism at the level of kidney. It involves failure to generate intracellular level of cAMP within distal tubular cells of kidney in response to AVP. Kidney specific V2 vasopressin receptor is defective in this disorder (either Xq28 gene or AQP2 gene is mutated).

Consequences:

The affected person feels excessive thirst and passes large amount of urine frequently. Even if a person drinks less amount of water, urine formation remains unaffected. The patient passes pale and diluted urine. Some of the complications of diabetes insipidus are :

• Dehydration: It can cause dry mouth, fever, headache, weight loss etc.
• Electrolyte Imbalance: It can cause nausea, cerebral edema, seizures, shock and even coma in serious conditions.
• Hypotension/ low blood pressure : Dizziness may occur due to low blood pressure which can damage heart and brain.
• Thrombosis: Due to decreased blood volume and circulatory fluids, heart is not able to pump properly and can cause shock to many body organs.

(B) CUSHING SYNDROME:

Causes:

Cushing syndrome occurs due to excessive and prolonged secretion and action of glucocorticoids.

Primary hypercortisolism may be due to an adrenal cortical tumor (adenoma or carcinoma). Cushing syndrome of secondary origin may derive from a pituitary tumor secreting excess of ACTH, or to ectopic ACTH production, or to pituitary corticotroph hyperplasia.

In patients with adrenal tumor, plasma cortisol levels are high but concentration of ACTH is low. But in bilateral adrenal hyperplasia, both plasma cortisol and ACTH levels are elevated.

Consequences:

Excess cortisol secretion can lead to central (truncal) obesity, hypertension, glucose intolerance, hirsutism, osteoporosis, polyuria, polydipsia and hyperpigmentation. Hyperglycemia may lead to steroid diabetes. The change in fat distribution is due to lipolytic action of ACTH but now insulin is exerting a lipogenic effect in some areas of the body. Loss of protein matrix of bones causes severe osteoporosis affecting spinal column. Excess of androgens produced are the cause of hirsutism in female. Hyperpigmentation may be present in Cushing's disease of secondary origin due to presence of increased circulating level of ACTH.

(C) ADDISON'S DISEASE:

Causes:

Addison's disease occurs due to insufficient amounts of cortisol and often aldosterone as well. These hormones give instructions to virtually every organ and tissue in our body.

Primary adrenocortical failure occurs when the adrenal gland is totally damaged which may be due to body attacking itself (autoimmune disease). Most often etiology is due to bilateral tubercular destruction of glands. Atrophy due to tuberculosis involves medulla as well as cortex whereas in idiopathic atrophy, only cortex is affected. In Addison's disease of secondary and tertiary origin, the defect may reside at the level of pituitary and hypothalamus respectively. A failure of hypothalamus to secrete CRH or absence of functional pituitary corticotrophs could explain the etiology of some forms of adrenal insufficiency.

Consequences:

Addison's disease cause extreme fatigue, weight loss, decreased appetite, hypotension, salt craving, hypoglycemia, muscle or joints pain, depression, nausea, diarrhea, increased melanin pigmentation of skin (because of absence of cortisol feedback of hypothalamus, which releases excessive ACTH), body hair loss or sexual dysfunction in women, high potassium and low sodium levels.

(D) GIGANTISM:

Causes:

Gigantism is almost always caused by a benign adenoma in the pituitary gland. An adenoma is a non-cancerous tumor and in case of gigantism causes secretion of too much growth hormone. Pituitary tumors can be small in size (micro-adenoma) or large (macro-adenoma). However, in gigantism they are frequently large and invade nearby brain tissue. The size of adenoma directly affects the signs and symptoms experienced by the individual.

Consequences:

Gigantism involves accelerated growth leading to above-normal expected height for a child of their age. The effect of growth hormone on bone, ligaments and soft tissue swelling can lead to coarse facial features, excessively large hands and feet with thick fingers and toes, prominent forehead and jaws.

Larger adenomas can damage the function of normal pituitary gland causing failure of secretion of other hormones. It may also cause headaches, visual field disturbances and nausea. In some cases, puberty may be delayed if pressure from adenoma on pituitary gland results in failure of sex hormone secretion and thus allows further growth of skeleton.

Gigantism may be complicated by diabetes, high blood pressure, enlargement of internal organs especially the heart.