Role of antidiuretic hormone in the abnormal water diuresis of anterior hypopituitarism in man.

To evaluate the role of antidiuretic hormone (ADH) in the defect in water excretion which is characteristic of glucocorticoid deficiency, the effects of hydrocortisone and ethanol upon urinary dilution during a sustained water load were studied in patients with anterior hypopituitarism. A spectrum of defects in urinary dilution was found in the seven patients with anterior hypopituitarism, and the subjects were separable into two groups. Four patients were unable to excrete a urine hypotonic to plasma (group I) while three diluted the urine (group II). In two of the group II patients, despite maintenance of hydration, urinary osmolality later rose to hypertonicity. Physiological doses of hydrocortisone improved urinary dilution in all patients. Submaximal doses of oral hydrocortisone, when given to the group I patients, converted their response to hydration to one characteristic of the group II patients, i.e., an initial hypotonic urine followed by a secondary rise to hypertonicity. Ethanol, a known inhibitor of ADH secretion, had no effect in the group I patients. When two of these patients were pretreated with sub-maximal doses of hydrocortisone, however, so that they were able to transiently dilute the urine, ethanol prevented the secondary rise in urine osmolality. Similarly, the administration of ethanol to the untreated group II patients, when the urine was hypotonic, improved diluting ability as characterized by a lowering of urinary osmolality and an increased excretion of solute-free water in all three patients. Hydrocortisone did not improve urinary dilution in three patients with complete hypophyseal diabetes insipidus and one with both anterior and posterior insufficiency receiving constant infusions of vasopressin. These data suggest, therefore, that inappropriately elevated levels of ADH play a major role in the defect in water excretion of anterior hypopituitarism. Glucocorticoids appear to be necessary for a normal neurohypophyseal response to inhibitory stimuli.