"Trace" contamination of corticotropin and human growth hormone with vasopressin--clinical significance.

Abstract

The occurrence of symptomatic hyponatremia during 48-hr ACTH infusions and the antidiuretic responses observed with human growth hormone (hGH) injections prompted an evaluation of the vasopressin (ADH) content of natural ACTH and hGH preparations in clinical use. In six normal subjects, 24-hr infusion of 80 U ACTH resulted in the retention of 88% of the infused fluid. A marked antidiuresis was observed in a diabetes insipidus patient given 40 U ACTH iv over a 2-hr period. ADH bioassay (rat) showed 13–18 mU ADH/U ACTH and 27–850 mU ADH/mg hGH. Synthetic ACTH had no ADH activity. This degree of ADH contamination together with iv infusion of fluids may explain the serious water intoxication observed with prolonged infusions of natural ACTH in hypopituitarism, and suggests fluid restriction and the use of synthetic ACTH to prevent this complication. The small ADH contamination of hGH and its mode of administration make serious hyponatremia during treatment unlikely