Cause:
Central: idiopathic (30%); pituitary tumor (Nejm 2000;343:998), sarcoid or eosinophilic granuloma; any CNS insult, eg, tumor, trauma, surgery; alcohol ingestion, transient, aggravates all other causes
Nephrogenic:
- Genetic, the “Hopewell hypothesis,” the ship on which 2 Scots came to US and spread via sex-linked recessive gene (Nejm 1988;318:881); but now know at least 2 different genes involved and may not be true (Nejm 1993;328:1534)
- Drug-induced: lithium (occurs in 20-70% who take); demethyltetracycline
- Transient in pregnancy due to increased vasopressinase (Nejm 1987;316:1070)
- Renal tubular damage from hypercalcemia, hypokalemia, chronic pyelonephritis, chronic partial obstruction, sickle cell anemia, aging, lead poisoning, renal tubular acidosis
Pathophys:Vasopressin (ADH) deficiency or resistance; normally it dilates splanchnic arterioles, increases renin, and stimulates factor VIII clotting factors; in kidney causes water resorption (Nejm 1988;318:881). Idiopathic central DI associated w lymphocytic infiltration of neurohypophyseal area and probably immune in etiology (Nejm 1993;329:683)
Pregnancy may unmask (Nejm 1991;324:522)
Sx:Excessive thirst and urination
Si:Hypovolemia
Mental retardation due to infantile dehydration
r/o PSYCHOGENIC WATER DRINKER who can partially concentrate urine with fluid restriction (Nejm 1981;305:1539)
Lab:
Chem:Na >145, at least when limit water po. Serum vasopressin decreased a little in psychogenic water drinker, markedly in central DI; elevated significantly in nephrogenic DI. 24-h urinary ADH in U/h is decreased in central DI, and elevated in nephrogenic DI. Uric acid elevated.
Urine:Specific gravity <1.019. If complaining of increased thirst but serum Na normal, then water-restrict and thereby dehydrate until q 1-h urine-specific gravities plateau; then compare this specific gravity with that after ADH (vasopressin) injection; or water-restrict to hypernatremia, getting coincident urine and serum osmoles. True DI patient will not get urine osmoles much >300, unlike psychogenic water drinker who can get urine osmoles 
600.
Xray:IVP shows dilated collecting system in genetic nephrogenic DI
MRI of pituitary in central type
Rx:
Acutely replace water deficit (24 Hour Requirements) at less than 12 mEq Na increase/24 h
of central type, desmopressin (vasopressin analog) 5-20 µgm nasal, sq, or iv q 4-20 h for complete type (Ann IM 1985;103:229). Desmopressin is resistant to vasopressinase (Nejm 1987;316:1070). For incomplete type, treat the same or treat like nephrogenic
of nephrogenic type: thiazides, carbamazepine (Nejm 1974;291:1234), or chlorpropamide (Nejm 1970;282:1266); amiloride 5-10 mg bid helps at least lithium type (Nejm 1985;312:408)