Key Points

• Diabetes insipidus is characterized by excessive dilute urine with thirst and polydipsia and results from decreased ADH secretion.

• Differential diagnosis of hypotonic polyuria includes neurogenic DI (vasopressin sensitive), nephrogenic DI (vasopressin resistant), and primary polydipsia.

• The water restriction test assists in diagnosis.

• Desmopressin is the primary treatment for central DI.

Clinical Features

Diabetes insipidus (DI) is characterized by the production of excessive dilute urine with secondary thirst and poly-dipsia. Polyuria is defined as 3 L or more of urine daily in adults and 2 L or more in children. Central DI may be familial or sporadic and is caused by head trauma, neuro-surgery, neoplasms, granulomas, infections, inflammation, chemical toxins, vascular disorders, congenital malformations, and genetic disorders. Other causes include hypoxic encephalopathy; infiltrative disorders, notably histiocytosis X (Hand-Schuller-Christian disease); anorexia nervosa; acute fatty liver of pregnancy; and Wolfram syndrome (central DI, diabetes mellitus, optic atrophy, and deafness) (Reddy and Mooradian, 2009). An autoimmune process is probably the cause of idiopathic DI and accounts for 30% to 50% of cases of central DI (de Bellis et al., 1999).

Thickening or enlargement of the posterior pituitary on MRI may represent lymphocytic infiltration and inflammation. Classically, DI after head trauma or neurosurgery has three phases: polyuria in the first 1 to 2 days after surgery, oliguria for

3 to 4 days, and culminating in a polyuric phase. These phases reflect the early paralysis of vasopressin-producing cells, followed by neuronal degeneration and massive ADH release, with subsequent permanent loss of vasopressin production.

Vasopressin-resistant DI is usually a familial disorder, although sporadic causes are recognized, as in chronic medullary kidney disease associated with sickle cell disease, multiple myeloma, amyloidosis, Sjogren's syndrome, and renal medullary cystic disease. In addition, prolonged primary polydipsia can wash out the normal medullary concentration gradient and may mimic ADH-resistant nephrogenic DI.


Although a variety of diseases may present as polyuria and polydipsia, thorough history and routine laboratory evaluation can narrow the differential diagnosis of hypotonic polyuria to three possibilities: neurogenic DI (vasopressin sensitive), nephrogenic DI (vasopressin resistant), or primary polydipsia (Mooradian and Morley, 1988).

Serum sodium concentrations less than 137 mEq/L and polyuria are usually manifestations of primary polydipsia. Patients with serum sodium concentration less than 143 mEq/L should have a water deprivation test after an overnight fast, with hourly measurement of body weight, urine volume, and osmolality. In severe cases the dehydration test can be started at 6 am. When the urine osmolality remains constant during three consecutive measurements, or if the patient loses more than 5% total body weight, plasma osmolality, ADH, and sodium concentrations are determined, and aqueous vasopressin (0.1 U/kg SC) or 10 ^.g of nasal desmopres-sin is administered and the response evaluated. An increase in urine osmolality of 150 mOsm/kg above baseline will exclude nephrogenic DI. In central DI, 10 ^.g of nasal desmopressin will result in increases in urine osmolality of as much as 800%. The response to desmopressin in partial central DI may result in urine osmolality increases of 15% to 50%. Patients with nephrogenic DI continue to have urine osmo-lality levels that remain below isosmotic. Primary polydipsia responds to the water deprivation test with urine concentrating to 500 mOsmol/kg or higher, compared with urine osmolality increasing to 800 mOsmol/kg or higher in normal subjects. Administration of exogenous vasopressin produces no further concentration in cases of primary polydipsia.

When the water suppression test yields equivocal results, the serum AVP concentration at baseline and after the water restriction test should be measured. However, the results of these tests may still be misleading because primary polydip-sia will result in submaximal secretion of AVP, mimicking the pattern of AVP secretion in partial central DI.


The treatment of choice for central DI is desmopressin. DDAVP can be administered IV, SC, nasally, or orally. An initial nasal inhalation of 5 ^.g is given at bedtime and increased by 5^g increments until nocturia is resolved, when a morning dose is given. The total daily dosage of nasal desmopressin is 5 to 20 ^.g daily. Oral desmopressin should be given on an empty stomach; absorption can be reduced by up to 50% when taken with food. A 0.1-mg tablet is equivalent to 2.5 to 5.0 ^.g of nasal spray (de Bellis et al., 1999).

Patients with partial DI will benefit from oral agents that potentiate AVP action or stimulate the release of AVP. These agents include chlorpropamide, carbamazepine, and clofi-brate. In such cases, desmopressin requirements may be lower than available preparations can provide. Patients with nephrogenic DI benefit from thiazide diuretics or indomethacin. Patients with DI should wear a medical alert bracelet. When the ability to drink fluids is impaired, intravenous hydration will be required to avoid dehydration and hypernatremia.

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