Evidence for the secretion of an antimineralocorticoid in congenital adrenal hyperplasia.

Plasma extracts from patients with congenital adrenal hyperplasia were found to contain substances that competed with aldosterone for mineralocorticoid receptor-binding sites in a rat kidney cytosol system. In normal subjects and patients with other disorders, the mineralocorticoid receptor-binding activity in such extracts could be entirely accounted for by the sum of the contributions of the steroids known to bind to the mineralocorticoid receptor. The secretion of these binding substances in patients with the C-21 hydroxylation defect was ACTH dependent. While these substances could be either mineralocorticoid agonists or antagonists, the latter is more likely. Production of mineralocorticoid antagonists would account for the compensatory hyperaldosteronism that occurs in the simple virilizing form, in which there is minimal impairment of aldosterone secretory reserve, and for the tendency to Addisonian crisis in patients with the salt-losing form, who have a more severe defect in aldosterone biosynthesis.