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Sequential Changes During Oral and Intravenous Metyrapone Administration

William Jubiz, MD; Shigeru Matsukura, MD; A. Wayne Meikle, MD; Gengo Harada, MD; Charles D. West, MD; Frank H. Tyler, MD

Arch Intern Med. 1970;125(3):468-471.

Abstract
Plasma metyrapone, adrenocorticotropic hormone (ACTH), cortisol, and deoxycortisol levels were measured sequentially in normal subjects during and after oral and intravenous metyrapone administration. Urinary 17-hydroxycorticosteroid (OHCS) values were determined before and after oral metyrapone administration. Though metyrapone levels were higher after intravenous administration, ACTH response to orally given metyrapone was greater, occurring mainly simultaneously with circadian rise of ACTH level. Plasma deoxycortisol levels paralleled those of ACTH. Urinary 17-OHCS manifested exaggerated diurnal variation especially the day after oral metyrapone administration, the changes corresponding to those of plasma ACTH and deoxycortisol levels. Concomitant hydrocortisone infusions abolished ACTH and deoxycortisol responses to orally given metyrapone only if the plasma cortisol level was above 7.5µg/100 ml. Daytime responses to metyrapone depend on the degree of inhibition of 11-β-hydroxylase. Nocturnal response is somehow related to the circadian rhythm of ACTH release.

Author Affiliations
Salt Lake City

From the Laboratory for the Study of Hereditary and Metabolic Disorders, Department of Medicine, University of Utah College of Medicine, Salt Lake City.

Footnotes
Received for publication Oct 7, 1969; accepted Nov 20.

Reprint requests to 50 N Medical Dr, Salt Lake City 84112 (Dr. Jubiz).

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