Diabetes Insipidus

In Diabetes Insipidus there is a failure to either produce ADH (more common) or for the kidney to respond to ADH (rare); in a sense, it is the opposite end of the spectrum from SIADH where there is too much ADH or oversensitivity to it. In DI there is almost pure water loss, often with maintenance of normal sodium balance. The mean age of onset is 16 years of age, with a slight male predominance.

Symptoms: Polyuria (urine output greater than 30mL/kg/day), polydipsia, dilute urine, nocturia, dehydration. May be otherwise asymptomatic, but severe cases will have symptoms of hypernatremia.

Diagnosis: Urine s.g. less than 1.005. Urine osmolality less than 200 mOsm/kg; serum osmolality will be normal (assuming patient has access to water) to slightly elevated: range 280-295 mOsm per kg. The water deprivation test is used to demonstrate central DI. Water is restricted until the patient is about 5% dehydrated and the urine reaches a steady-state osmolarity. A test dose of ADH is then administered. In normal patients and those with nephrogenic DI, the urine osmolarity will change less than 5 mOsm/kg. In complete central DI, the osmolarity will double; in partial central DI, there will be an intermediate effect.

Treatment: A patient presenting acutely with DI and hypernatremia should be treated for the hypernatremic dehydration. In the longer term, neurogenic may respond to nasal desmopressin (a synthetic analog of ADH). Nephrogenic requires good hydration and monitoring of electrolytes. Thiazide and amiloride may relieve symptoms by depleting total body salt and forcing increased reabsorbtion in the proximal convoluted tubule. The oral hypoglycemic agent chlorpropamide can be used to stimulate ADH secretion in cases of partial central DI, although its use is limited by hypoglycemia. Carbamazepine and clofibrate also stimulate ADH secretion.

Etiologies:

Central (Neurogenic)

Nephrogenic

Primary

Nonfamilial

Congenital

Secondary

Head Trauma

Surgery

Tumor (craniopharyngioma)

Granuloma (sarcoid, TB, Wegeners, syphilis)

Infection (encephalitis, meningitis)

Histiocytosis

Ischemia (shock, Sheehan's Syndrome)

Vascular (aneurysm, hemorrhage, vasculitis)

Vaso-occlusive (sickle cell, thrombosis)

Primary

X-linked (defective V2 receptor)

Autosomal recessive (defect in aquaporin channel)

Secondary

Renal Disease

dysplasia

obstructive uropathy

reflux

cystic diseases

tubulo-interstitial nephritis

RTA

hypokalemia or hypercalcemia

systemic disease with renal involvement

(SSD, amyloidosis, sarcoidosis, Sjorgren's)

Drugs Inhibiting ADH Release:

Systemic alpha-adrenergic agonists
Ethanol
Opiate antagonists
diphenylhydantoin
clonidine
CO poisoning

Drugs Inhibiting Peripheral ADH Action:

Lithium (inhibits cAMP/decreased DCT reabsorbtion)
Demeclocycline (reversibly inhibits cAMP)
Methoxyflurane (increases serum fluoride level)
Amphotericin B
Cisplatin
Cyclophosphamide
Propoxyphene
Angiographic Dyes
Osmotic Diuretics

Net Scut Home

Please direct all comments to:

Last modification: June 10, 1998