Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
Medicover Oldenburg MVZ, Oldenburg, Germany.
Front Endocrinol (Lausanne). 2022 Jun 13;13:903545. doi: 10.3389/fendo.2022.903545. eCollection 2022.
Although surgery is considered the first-line treatment for patients with endogenous Cushing's syndrome (CS), medical therapy is often required to control severe hypercortisolism. Metyrapone and osilodrostat are both steroidogenic inhibitors targeting the 11β-hydroxylase, however, their therapeutic effectiveness has not yet been directly compared. This study aimed to evaluate metyrapone and osilodrostat in the short-term therapy of CS.
Retrospective analysis of patients with endogenous CS treated with metyrapone or osilodrostat as monotherapy for at least 4 weeks. Main outcome measures were serum cortisol and 24h urinary free cortisol (UFC) at baseline (T0) and after 2 (T1), 4 (T2), and 12 weeks (T3) of therapy.
16 patients with endogenous CS were identified (pituitary n=7, adrenal n=4, ectopic CS n=5). Each 8 patients were treated with metyrapone and osilodrostat. Despite heterogeneity, both groups showed comparable mean UFC levels at T0 (metyrapone: 758 µg/24h osilodrostat: 817 µg/24h; =0.93). From T0 to T1, the decrease of UFC was less pronounced under metyrapone than osilodrostat (-21.3% -68.4%; median daily drug dose: 1000 mg vs 4 mg). This tendency persisted at T2 (-37.3% vs -50.1%; median drug dose: 1250 mg 6 mg) while at T3 a decrease in UFC from T0 was more pronounced in the metyrapone group (-71.5% -51.5%; median dose 1250 mg 7 mg). Under osilodrostat, a QTc-interval prolongation was identified at T3 (mean 432 ms vs 455 ms). From T0 to T2, the number of antihypertensive drugs remained comparable under metyrapone and decreased under osilodrostat (n= -0.3 n= -1.0).
Although both drugs show comparable therapeutic efficacy, osilodrostat seems to reduce cortisol levels and to control blood pressure faster.
尽管手术被认为是治疗内源性库欣综合征(CS)患者的一线治疗方法,但通常需要药物治疗来控制严重的皮质醇增多症。美替拉酮和奥昔拉酮都是针对 11β-羟化酶的甾体生成抑制剂,然而,它们的治疗效果尚未进行直接比较。本研究旨在评估美替拉酮和奥昔拉酮在 CS 的短期治疗中的作用。
回顾性分析了至少接受美替拉酮或奥昔拉酮单药治疗 4 周以上的内源性 CS 患者。主要观察指标为治疗前(T0)、治疗后 2 周(T1)、4 周(T2)和 12 周(T3)时的血清皮质醇和 24 小时尿游离皮质醇(UFC)。
共确定了 16 例内源性 CS 患者(垂体 n=7,肾上腺 n=4,异位 CS n=5)。每组 8 例患者分别接受美替拉酮和奥昔拉酮治疗。尽管存在异质性,但两组患者在 T0 时的 UFC 平均水平相似(美替拉酮:758μg/24h,奥昔拉酮:817μg/24h;=0.93)。从 T0 到 T1,美替拉酮组 UFC 的下降幅度小于奥昔拉酮组(-21.3%至-68.4%;中位数日剂量:1000mg 比 4mg)。这种趋势在 T2 时仍然存在(-37.3%至-50.1%;中位数药物剂量:1250mg 比 6mg),而在 T3 时,美替拉酮组从 T0 开始 UFC 的下降幅度更为明显(-71.5%至-51.5%;中位数剂量 1250mg 比 7mg)。在奥昔拉酮组中,T3 时 QTc 间期延长(平均 432ms 比 455ms)。从 T0 到 T2,美替拉酮组的降压药物数量保持不变,而奥昔拉酮组减少(n=-0.3 比 n=-1.0)。
尽管两种药物的治疗效果相似,但奥昔拉酮似乎能更快地降低皮质醇水平并控制血压。