LAUSR

OBJECTIVE Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist. DESIGN We investigated the renin-angiotensin-aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody®) compared to standard glucocorticoid (GC) therapy. METHODS Data was analyzed from the 6-month, phase 3 study of MR-HC (n = 42) vs standard GC therapy (n = 41). MC replacement therapy remained unchanged throughout the study. Blood pressure, serum potassium, serum sodium, plasma-renin-activity (PRA) and serum 17OHP and androstenedione concentrations were analyzed at baseline, 4, 12 and 24 weeks. RESULTS The median serum 17OHP in the morning was significantly lower on MR-HC compared to standard GC at 24 weeks (2.5 (IQR 8.3) nmol/l vs 10.5 (IQR 55.2) nmol/l, p = 0.001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 (IQR 1.0) ng/l/s to 0.48 (IQR 0.61) ng/l/s, p = 0.012) but not in patients on standard GC (0.53 (IQR 0.66) ng/l/s to 0.52 (IQR 0.78) ng/l/s, p = 0.613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol/l to 139.3 ± 1.8 mmol/l, p = 0.047), but remained unchanged on standard GC (139.8 ± 1.6 mmol/l to 139.3 ± 1.9 mmol/l, p = 0.135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels. CONCLUSION 6 months of MR-HC therapy decreased PRA and increased sodium levels indicating a greater agonist action of the 9α-fluorocortisol dose, which may be due to the decreased levels of the MC-receptor antagonist 17OHP.