The effect of different treatment regimens on hormonal profiles in congenital adrenal hyperplasia.

Optimal steroid therapy for patients with congenital adrenal hyperplasia (CAH) is still controversial. While hydrocortisone suppression therapy (20–25 mg/m2·day) has received acceptance, the use of nocturnal synthetic glucocorticoids and the control of renin secretion by mineralocorticoids have recently been recommended. To determine the relative merits of these treatments, hormonal profiles have been obtained in six patients (aged 10–16 yr; three with salt wasting and three with simple virilizing 21-hydroxylase CAH) who were stabilized for at least 3 months on 1) nocturnal dexamethasone (0.25–0.75 mg/ day) and 2) twice daily hydrocortisone (25 mg/m2·day) therapy. The effect of changes in mineralocorticoid therapy was also studied. Profiles for cortisol, 17-hydroxyprogesterone (17OHP), and ACTH were determined by hourly venous sampling for 24 h. Nocturnal secretion of ACTH and renin (PRA) was assessed by half-hourly sampling from 0200–0800 h. GH secretion was assessed by sampling during slow wave sleep. Plasma ACTH was detectable at some time of the day in all patients on all regimes studied but was higher in the early morning in patients on hydrocortisone. Plasma 17OHP was detectable in all but one patient, and a clear reciprocal relationship with plasma cortisol levels was evident, although the pattern of secretion depended on the type of treatment regimen. PRA was lower on hydrocortisone therapy, but nocturnal fluctuations of PRA showed no correlation with plasma ACTH, plasma 17OHP, or urine pregnanetriol excretion. Changes in mineralocorticoid therapy had no consistent effect on ACTH, 17OHP, or urine pregnanetriol. GH secretion during sleep was normal on both glucocorticoid regimens and there was no consistent change in growth velocity. Plasma 17OHP correlated well with urine pregnanetriol, but the optimum sampling time depended on the treatment regimen. It is concluded that 1) neither regimen normalizes ACTH or adrenal precursor secretion; 2) mineralocorticoid therapy is not a major determinant of ACTH or glucocorticoid precursor secretion in CAH; and 3) plasma 17OHP accurately reflects pregnanetriol excretion provided treatment regimen and sampling time are considered, but plasma ACTH does not.