RESPONSE OF PLASMA 17,21-DIHYDROXY-20-KETOSTEROIDS TO REPOSITORY CORTICOTROPIN

Abstract

THE widespread use of long-term therapy with corticotropin (ACTH) in the treatment of numerous medical disorders has stimulated the search for a potent and long-acting intramuscular repository form. The introduction of corticotropin in gelatin (Gel-ACTH) in 1952 and more recently corticotropin with zinc hydroxide (Zn-ACTH) have made available two such preparations for clinical use. The sustained effectiveness of a single intramuscular dose of these preparations has been measured in the past primarily by indirect laboratory tests of increased function of the adrenal cortex and by the clinical responsiveness to therapy. Levin (1) reported clinical improvement for twelve to twenty-four hours following one injection of 40 to 60 units of Gel-ACTH. Thorn (2) reported a depression in the number of circulating eosinophils and an increase in the urinary excretion of neutral 17-ketosteroids for twelve to twenty-four hours following a single injection of the same repository preparation. Zn-ACTH was studied by Greene (3), den Oudsten (4), and Turner (5) who reported a depression in the number of circulating eosinophils, an increase in the urinary excretion of neutral 17-ketosteroids and clinical improvement for a period of twenty-four to forty-eight hours following a single injection. More recently, Bayliss (6) studied the adrenocortical response to the administration of Gel-ACTH by measuring the plasma 17-hydroxycorticoids. He found that 80 units of this preparation given intramuscularly caused an elevation of the 17-hydroxycorticoid plasma levels for four to eight hours, whereas 20 units given by the same route resulted in a peak response at two to four hours.