11-β-Hydroxylase Deficiency: Steroid Response to Sodium Restriction and ACTH Stimulation¹

Abstract

Two siblings with congenital virilizing adrenal hyperplasia, due to 11-β-hydroxylase deficiency, are presented. Urinary excretion and secretion rates of aldosterone and deoxycorticosterone (DOC) and plasma renin activity (PRA) were studied during a control period, a low-sodium diet, dexamethasone therapy and ACTH stimulation. During the low-sodium period, there was no negative sodium balance, DOC remained high, aldosterone and PRA undetectable. With dexamethasone and a low-sodium diet, sodium balance was negative at first, then DOC decreased, aldosterone and PRA increased and sodium balance became positive. ACTH for 48 hr increased aldosterone and DOC and did not change PRA. The persistent DOC rise was associated with further reduced aldosterone secretion. The adrenal glands in these two children were then able to synthetize aldosterone in the zona glomerulosa after ACTH stimulation and through the renin-angiotensin system. The mechanisms are not clear: the data could be explained either by an incomplete 11-β-Phydroxylase block or an alternate pathway. In either case, DOC above certain levels seemed to have an inhibitory action on ll-β-hydroxylase activity necessary for aldosterone synthesis.