On the role of antidiuretic hormone in the inhibition of acute water diuresis in adrenal insufficiency and the effects of gluco- and mineralocorticoids in reversing the inhibition.

In order to determine whether or not antidiuretic hormone (ADH) is essential to the inhibition of an acute water diuresis in adrenal insufficiency, the response to oral water loads was tested in rats with hereditary hypothalamic diabetes insipidus (DI) which lack ADH. It was found that 60 min after water loads of 3 or 5% of body weight urine flow was significantly lower and urine osmolality significantly higher in adrenalectomized DI rats than in the same DI rats before removal of their adrenal glands. The efficacy of gluco- and mineralocorticoids in reversing the inhibition was then determined in the same adrenalectomized DI rats. Prednisolone alone, administered either acutely or chronically, restored the response in urine flow to that seen in the same rats before adrenalectomy, but failed to correct the defect in urinary dilution. Aldosterone when given alone tended to correct the diluting ability but not the response in urine flow. When these two adrenal cortical hormones were given simultaneously, both the urine flow and urine osmolality were nearly identical to what they had been in the same DI rats before adrenalectomy. These studies strongly suggest (a) that ADH is not essential to the inhibition of an acute water diuresis in adrenal insufficiency, although it may abet the inhibition in individuals without diabetes insipidus, which can elaborate ADH; and (b) that both gluco- and mineralocorticoids are required in adrenal insufficiency in order to fully restore the water diuresis as judged by the dual criteria of urine flow and urine osmolality.