Increased renal sensitivity to vasopressin in two patients with essential hypernatremia

Patients with essential hypernatremia maintain urinary concentrating ability despite plasma hyperosmolality and low plasma vasopressin concentrations. We investigated renal sensitivity to ultralow dose vasopressin infusions in two patients with a syndrome of hypodipsia, hypernatremia with selective osmoreceptor dysfunction, early puberty, and aggressive behavior. The patients were water loaded until a hypotonic diuresis was established. Vasopressin was infused in stepwise increments from 0.4-12 fmol/kg X min. Both patients had increased renal sensitivity to vasopressin, achieving negative free water clearance at infusion rates of 0.4 and 4 fmol/kg X min (normal greater than or equal to 6). Treatment for 3 months with 1-desamino-8-D-arginine vasopressin (DDAVP) led to an improvement in behavior and the reporting, for the first time, of a sensation of thirst. After DDAVP therapy both patients had a reduction of their renal sensitivity to infused vasopressin. We conclude that untreated patients with essential hypernatremia have increased renal sensitivity to vasopressin which is reduced by DDAVP administration.