The interrelationship of sodium balance, plasma renin activity and acth in congenital adrenal hyperplasia

Metabolic studies in seven children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency revealed that all subjects displayed abnormalities in sodium balance which ranged from borderline depletion in the simple virilizers detectable only by high levels of plasma renin activity to overt salt-loss and hypovolemia in the salt-losers. These abnormalities suggested that aldosterone biosynthesis was relatively impaired in all subjects, but more in the saltlosers. Sodium depletion, while on constant glucocorticoid replacement therapy, induced marked elevations of plasma renin activity which was associated with a hypersecretion of ACTH, with levels often over 1000 pg/ml. However, individuals whose hypothalamic-pituitary axis was completely suppressed with dexamethasone did not show a rise in ACTH levels. The degree of ACTH stimulation was significantly correlated with the levels of plasma renin activity (r = 0.811, P < 0.001) and was proportional to the degree of sodium loss, thus representing an indirect index of the severity of the enzymatic deficiency. A significant percentage of the total plasma ACTH immunoreactivity was biologically active in stimulating steroidogenesis since the rise in ACTH resulted in hypersecretion of adrenal androgens and glucocorticoid precursors. Sodium repletion and long term mineralocorticoid therapy normalized the sodium balance, plasma renin activity and ACTH levels inducing almost complete suppression of adrenal secretion. The metabolic effects of sodium balance observed revealed the existence of an interrelationship between the renin-angiotensin system and the pituitary-adrenal axis. These studies suggest that all patients with CAH and elevated levels of plasma renin activity, both salt-losers and simple virilizers, would benefit from treatment with mineralocorticoids for optimal hormonal control of the disease.