Glomerulosa failure in congenital adrenocortical unresponsiveness to ACTH

We report two children of a family with congenital adrenocortical unresponsiveness to ACTH. Repeated stimulation of the adrenal by Synthetic 1-24 ACTH (Synacthen) failed to increase cortisol secretion, but produced significant rises of serum aldosterone. This was, however, associated with increased plasma renin activity. Only when the renin-angiotensin effect was eliminated, by a converting enzyme blocker, did Synacthen fail to affect serum aldosterone. These data support the view that glucocorticoid deficiency in this disorder results from unresponsiveness to ACTH and that development of the zona glomerulosa and normal aldosterone secretion is achieved by action of the renin-angiotensin system.