Tschaidse Lea, Reisch Nicole, Arlt Wiebke, Brac de la Perriere Aude, Linden Hirschberg Angelica, Juul Anders, Mallappa Ashwini, Merke Deborah P, Newell-Price John D C, Perry Colin G, Prete Alessandro, Rees D Aled, Stikkelbroeck Nike M M L, Touraine Philippe A, Coope Helen, Porter John, Ross Richard John M, Quinkler Marcus
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, United Kingdom.
Eur J Endocrinol. 2023 Jan 10;188(1). doi: 10.1093/ejendo/lvac006.
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.
We investigated the renin-angiotensin-aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy.
Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus 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.
The median serum 17OHP in the morning was significantly lower on MR-HC compared with standard GC at 24 weeks (2.5 nmol L-1 (IQR 8.3) versus 10.5 nmol L-1 (IQR 55.2), P = .001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 ng L-1 s-1 (IQR 1.0) to 0.48 ng L-1 s-1 (IQR 0.61), P = .012) but not in patients on standard GC (0.53 ng L-1 s-1 (IQR 0.66) to 0.52 ng L-1 s-1 (IQR 0.78), P = .613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol L-1 to 139.3 ± 1.8 mmol L-1, P = .047), but remained unchanged on standard GC (139.8 ± 1.6 mmol L-1 to 139.3 ± 1.9 mmol L-1, P = .135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels.
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.
盐耗失型（SW）先天性肾上腺皮质增生症（CAH）患者若病情控制不佳，往往需要高剂量的9α-氟皮质醇，因为他们的17-羟孕酮（17OHP）水平较高，而17OHP是一种盐皮质激素（MC）受体拮抗剂。
我们对接受每日两次缓释氢化可的松（MR-HC，商品名Efmody）治疗的SW-CAH患者与接受标准糖皮质激素（GC）治疗的患者的肾素-血管紧张素-醛固酮系统进行了研究。
分析了MR-HC（n = 42）与标准GC治疗（n = 41）的6个月3期研究数据。在整个研究过程中，MC替代疗法保持不变。在基线、4周、12周和24周时分析血压、血清钾、血清钠、血浆肾素活性（PRA）以及血清17OHP和雄烯二酮浓度。
在24周时，与标准GC相比，接受MR-HC治疗的患者早晨血清17OHP中位数显著降低（2.5 nmol L-1（四分位间距8.3）对10.5 nmol L-1（四分位间距55.2），P = .001）。接受MR-HC治疗的患者PRA从基线到24周显著降低（0.83 ng L-1 s-1（四分位间距1.0）降至0.48 ng L-1 s-1（四分位间距0.61），P = .012），而接受标准GC治疗的患者则无显著变化（0.53 ng L-1 s-1（四分位间距0.66）至0.52 ng L-1 s-1（四分位间距0.78），P = .613）。接受MR-HC治疗的患者血清钠浓度从基线到24周升高（138.8 ± 1.9 mmol L-1至139.3 ± 1.8 mmol L-1，P = .047），而接受标准GC治疗的患者保持不变（139.8 ± 1.6 mmol L-1至139.3 ± 1.9 mmol L-1，P = .135）。收缩压、舒张压和血清钾水平未见显著变化。
6个月的MR-HC治疗降低了PRA并提高了钠水平，表明9α-氟皮质醇剂量的激动作用更强，这可能是由于MC受体拮抗剂17OHP水平降低所致。
