Studies on the Deficiency of 21-Hydroxylation in Patients with Congenital Adrenal Hyperplasia1

Abstract

This study was designed to investigate the degree of 21-hydroxylase deficiency in the pathways leading to production of cortisol and aldosterone in the 2 clinical variants of 21-hydroxylase deficiency—salt-losers and non-salt-losers. Five patients with congenital adrenal hyperplasia resulting from deficiency of 21-hydroxylation were studied: 3 of these patients were salt-losers and the other 2 were non-salt-losers. Three normal volunteers were used as controls. All subjects were studied on an air-conditioned unit under strict metabolic conditions including constant diet and restricted activity, and each received each day 109–120 mEq of sodium. Sodium and potassium were measured in 24-hr urine pools and all sodium losses were replaced. The patients were studied off treatment and again after they had received ACTH intramuscularly, 20 U/m² of body surface every 12 hr. Plasma progesterone, 17-hydroxyprogesterone and renin activity, aldosterone secretion rate, and urinary 17-hydroxysteroids and 17-ketosteroids were measured in all patients “off” treatment and after completion of a period of ACTH administration. The plasma progesterone, 17-hydroxyprogesterone and renin activity were elevated in all patients “off” treatment and were lower after ACTH. The ASR was elevated in 2 non-salt-losers and high normal in the one salt-loser who had the highest plasma progesterone and plasma renin activity and was low in the other 2 salt-losers. Thus, the 2 clinical variants cannot be distinguished on the basis of aldosterone secretion rate alone. Apparently, salt-losers with defective 21-hydroxylase for progesterone can in part compensate for the defect with very high concentrations of substrate (progesterone) and stimulus (angiotensin).