The steroid response to controlled adrenal stimulation in congenital adrenal hyperplasia

Adrenal steroidogenesis has been studied in vivo in eleven patients aged 13-68 years with 21-hydroxylase deficiency, in one patient with 11 beta-hydroxylase deficiency and in ten female control subjects. Serum levels of the delta 5 3 beta-hydroxysteroids, pregnenolone (Pe), 17 alpha-hydroxypregnenolone (17Pe), dehydroepiandrosterone (DHEA) and androstenediol (Adiol) and their delta 4 3-keto counterparts, progesterone (Po), 17 alpha-hydroxyprogesterone (17Po) androstenedione (Adione) and testosterone as well as of 11-deoxycortisol and cortisol were measured during acute adrenal suppression with dexamethasone followed by stimulation with synthetic 1-24 ACTH. In the seven patients with 21-hydroxylase deficiency who were on adequate glucocorticoid therapy, grossly exaggerated responses of 17Po and Po to ACTH were nevertheless preserved. In contrast, there was a grossly subnormal response of 17Pe, DHEA and Adiol to ACTH, and low basal levels of DHEA-sulphate. In the untreated patients the response of 17Pe and DHEA was normal. The Adione response was exaggerated in untreated and normal in treated cases. Similar findings obtained in the patient with 11 beta-hydroxylase deficiency who was studied after 6 weeks without replacement therapy. Our findings demonstrate that production of adrenal steroids that are associated with the adrenarche is not exaggerated in untreated CAH, and is grossly suppressed in treated cases. These findings are compatible with the hypothesis that intra-adrenal cortisol may initiate and/or maintain production of the delta 5 steroids by the zona reticularis that occurs in the human adrenarche.