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Intranasal Administration of Adrenocorticotropin-(1–24) Stimulates Adrenocortical Hormone Secretion

First Department of Internal Medicine, Toho University School of Medicine (N.H., T.I., H.U., Y.M.), Tokyo 143-0015, Japan; and Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (N.H.), Bethesda, Maryland 20892-1583

Address all correspondence and requests for reprints to: Naoki Hiroi M.D., First Department of Internal Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo 143-0015, Japan. E-mail: . n-hiroi{at}tkf.att.ne.jp

Abstract

To determine the efficiency of transmucosal absorption of ACTH, we measured serum cortisol, aldosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) levels after intranasal (in) vs. iv administration of ACTH-(1–24) (250 µg) in 12 healthy adult men (mean age, 24.3 ± 3.2 yr; range, 21–31 yr), who had received no prior medication and had no symptoms of rhinitis. Blood was collected at 0, 30, 60, 120, and 180 min after administration of ACTH-(1–24), and the levels of adrenocortical steroids were measured by specific RIAs. There were no side-effects associated with in or iv ACTH administration. After in administration, serum cortisol and aldosterone increased rapidly by 224.7 ± 39.2% and 147.2 ± 50.5%, respectively, peaking 30 min after ACTH-(1–24) administration, and decreasing to basal levels within 120 min. These increases in serum cortisol and aldosterone were lower than those obtained after iv administration. Thirty minutes after in or iv administration of ACTH-(1–24), DHEA increased by 49.1 ± 27.2% and 81.6 ± 17.1%, respectively, and remained elevated for 180 min. Serum DHEA-S levels did not change after in administration of ACTH-(1–24) and increased only slightly after iv injection. Adrenocortical steroid levels did not increase after in administration of saline. These data demonstrate that adrenocortical steroids are stimulated by in administration of ACTH-(1–24). We suggest that intranasal administration of ACTH offers both a diagnostic approach as an adrenal function test and a therapeutic approach as ACTH replacement therapy in patients with ACTH deficiency. The latter may be more physiological than glucocorticoid replacement.