Wednesday, September 21, 2011

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Diabetes insipidus

Definition:
It is a syndrome characterized by the production of abnormally large volumes of dilute urine due to the decreased secretion or decreased action of AVP (arginine vasopressin). AVP is also commonly known as ADH i.e. Anti Diuretic Hormone.

Cause:
1) Central D.I - aka pituitary D.I or neurohypophyseal D.I.
2) Nephrogenic D.I

Central D.I occurs because of an inadequate release of ADH from the posterior pituitary. The usual causes are idiopathic, traumatic, iatrogenic (surgery,radiation), neoplastic, infective, granulomatous (TB,sarcoidosis) and congenital being a rarer cause.

Nephrogenic D.I is due to the resistance to ADH at the level of the collecting duct cell. The most common cause of resistance is the use of drugs like lithium (bipolar disorders) and amphotericin. But it can rarely be due to a congenital cause.

Pathogenesis:
The antidiuretic effect of ADH is achieved by increasing the hydroosmotic permeability of cells that line the distal tubule and medullary collecting ducts of the kidney. In the absence of AVP, these cells are impermeable to water and reabsorb little, if any, of the relatively large volume of dilute filtrate that enters from the proximal nephron. Thus there is production of large amounts of dilute urine.

Clinical features:
1) Polyuria - more than 50 mL/kg of urine per day (i.e. 3500 mL for a 70 kg man) with nocturia also,
2) Polydipsia due to excessive thirst,
3) Preference for ice water.

Investigations:
1) 24 hr urine sample will show a urine output > 50 mL/kg body weight,
2) 24 hr urine osmolarity will be < 300 mosmol/L,
3) Fluid deprivation test - no increase in urine osmolarity,
4) Administration of desmopressin at 0.03 μg/kg S.C or I.V and measurement of urine osmolarity 2 hr later -
An increase of >50% indicates severe pituitary DI, whereas a smaller or absent response is strongly suggestive of nephrogenic DI.

Treatment:
Desmopressin is a synthetic analogue of ADH and is a V2 receptor agonist that eliminates polyuria and polydipsia in central D.I. It can be given SC,IV,oral or intranasally. The last method is preferred and the dosage is 0.15-0.75 μg/kg.
The main side effect is water intoxication that is manifested as hyponatremia.

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