The Origin of Plasma Deoxycorticosterone in the Syndrome of Congenital Adrenal Hyperplasia and in Acute States of Adrenocorticotropin Excess*

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Abstract
Studies in men and women indicate that plasma deoxycorticosterone (DOC) is derived both from direct secretion and also peripheral conversion from progesterone (Prog), particularly in the luteal phase of the cycle. The present work explored the role of direct DOC secretion vs. peripheral conversion of Prog to DOC during acute ACTH stimulation and in a chronic state of ACTH excess, congenital adrenal hyperplasia (CAH). Intravenous ACTH (Cortrosyn; 250 μg for 2 h) in four normal men increased plasma Prog 4-fold, while plasma DOC increased from 8 to 39 ng/dl. The MCR and the conversion ratio of Prog to DOC (CRProgD0C) were determined under steady state conditions using the constant infusion technique with [3H]Prog. The calculated MCRProg was 1419 liters/m2·day, compared to 1176 ± 45 previously measured in adults. The calculated morning blood production of Prog after ACTH stimulation was 550 μg/m2·day. We estimated the blood production of DOC by using the plasma levels of DOC and our previously reported MCRDOC (14). Blood production of DOC after ACTH was estimated to be 330 μg/m2·day. Normal male PRProg and DOC values are 118 and 54 μg/m2·day, respectively (10). The CRProgDOC during ACTH stimulation was 1%, which is not different from previously reported normal values of 1.3 ± 0.2%. The calculated amount of DOC derived from peripheral conversion was only 2%. Similar studies were performed on four other men given metyrapone (750 mg orally every 4 h for 24 h). In all studies, plasma 11-deoxycortisol (S) increased more than 7 μg/dl. Plasma Prog increased from 10 to 277 ng/dl, while DOC increased from 8 to 3600 ng/dl. The CRProgDOC was 1.4%. Again, despite the rise in Prog, the contribution via peripheral conversion was negligible. Studies were performed in four patients with CAH. One patient had the salt wasting as well as the virilizing syndrome. In the untreated state, plasma Prog was markedly increased (400–1700 ng/dl), as was plasma DOC (52–67 ng/dl). The conversion ratio was 1.8%. The calculations indicate that 25–44% of plasma DOC was derived from conversion of Prog in patients with the virilizing form of CAH. The contribution of Prog was less (5%) in the salt loser, since the Prog production was lower. This study and our previous work (10) indicate that neither sex, age, nor ACTH alters the peripheral conversion rate of Prog to DOC. The acute effect of ACTH is to increase DOC blood production by direct adrenal secretion. However, in CAH, the enzyme block and chronic ACTH stimulation are associated with an increase in the prehormone Prog, so that it is the source of a quarter to a third of the plasma DOC. Despite 21-hydrox-ylase deficiency of the adrenal cortex, peripheral 21-hydroxyla-tion appears intact, suggesting that peripheral enzyme activity i s not increased.