Antidiuretic Effect and Complications of Chlorpropamide Therapy in Diabetes Insipidus

Abstract

Short and longer term studies of the antidiuretic effect of chlorpropamide have been undertaken in 5 patients with diabetes insipidus secondary to a known hypothalamic or pituitary lesion (Group 1), 6 patients with idiopathic diabetes insipidus (Group 2), and 1 patient with familial nephrogenic diabetes insipidus. Of the 11 patients in Groups 1 and 2 complete control of the diabetes insipidus with chlorpropamide alone (in doses varying from 50 to 500 mg/day) was achieved in 6. Five of these 11 patients could only be fully controlled by the combination of chlorpropamide and hydrochlorothiazide. Chlorpropamide had no effect in the patient with nephrogenic diabetes insipidus. Symptomatic hypoglycemia was noted in 2 of the Group 1 patients, this problem being avoided by reducing the chlorpropamide dose. Severe hypoglycemia occurred during chlorpropamide therapy in the 1 patient with nephrogenic diabetes insipidus. Water retention with dilutional hyponatremia and symptoms of water intoxication occurred in 1 of the Group 1 patients, and probably occurred in another patient in this group. These studies support, but do not prove, the hypothesis that chlorpropamide exerts its antidiuretic action in diabetes insipidus by sensitizing the distal tubule to an otherwise insufficient concentration of circulating ADH.