The Role of Renin and Angiotensin in Salt-Losing, 21- Hydroxylase-Deficient Congenital Adrenal Hyperplasia*

Abstract

Seven children with salt-losing, 21-hydroxylasedeficient congenital adrenal hyperplasia (CAH) who had been off mineralocorticoids for several years were studied before and after reinstitution of mineralocorticoid therapy. Ten children with nonsalt-losing CAH were controls. Initially, the seven subjects showed clinical evidence of poor control despite suppressive doses of hydrocortisone; five exhibited coincidental signs of glucocorticoid excess. After treatment with Florinef (0.1 mg orally twice daily) for 3 months, they reported decreased fatigue and salt craving, and four had decreased hydrocortisone requirements. There was no hypertension. Reinstitution of mineralocorticoid therapy resulted in a marked improvement in all chemical parameters measured. Serum 17-hydroxyprogesterone fell from 19,134 ± 1134 ng/dl (mean ± SEM) before treatment to 239 ± 49 ng/dl at 3 months of therapy; the control group had a level of 902 ± 318 ng/dl. PRA fell from 21.7 ± 1.9 to 2.5 ± 0.8 ng/mlh, indistinguishable from that of the control group (2.2 ± 0.7 ng/ml'h) and within normal limits. Twenty-four-hour urinary 17- ketosteroids and pregnanetriol also showed marked drops and approached normal at 3 months. Plasma ACTH levels were not elevated before or after therapy. Plasma aldosterone levels were markedly elevated initially (mean value, 55.3 ng/dl) and normalized with therapy (mean value, 17.3 ng/dl). There was a positive correlation between PRA and serum 17-hydroxyprogesterone (P < 0.001), and plasma aldosterone and serum 17-hydroxyprogesterone (P < 0.01). We thus conclude that: 1) children with 21-hydroxylase-deficient CAH can produce large amounts of aldosterone, the effects of-which are antagonized by high levels of substances such as 17-hydroxyprogesterone; 2) the renin-antiotensin system can stimulate all zones of the adrenal cortex, and elevated PRA can lead to poor control in salt-losing CAH just as can inadequate suppression of ACTH; 3) salt-losers need mineralocorticoid as well as glucocorticoid replacement for optimal control; and 4) salt losers should be maintained on mineralocorticoids for life.