Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients.
Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients.
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DOI：
10.1210/jc.2015-2616
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发表时间：
2015-11
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通讯作者：
Newell-Price J
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作者：
Daniel E;Aylwin S;Mustafa O;Ball S;Munir A;Boelaert K;Chortis V;Cuthbertson DJ;Daousi C;Rajeev SP;Davis J;Cheer K;Drake W;Gunganah K;Grossman A;Gurnell M;Powlson AS;Karavitaki N;Huguet I;Kearney T;Mohit K;Meeran K;Hill N;Rees A;Lansdown AJ;Trainer PJ;Minder AE;Newell-Price J
库欣综合征(CS)是一种严重的疾病，死亡率高，发病率高，需要控制高皮质醇血症。很少有资料记载类固醇生成抑制剂甲替拉酮用于这一目的。该研究的目的是评估美替拉酮在控制同期一系列CS患者皮质醇过量方面的有效性。这项研究是一项多中心的回溯性研究。对13所大学医院进行了研究。我们研究了195例确诊为CS的患者：115例库欣病，37例异位ACTH综合征，43例ACTH非依赖性疾病(肾上腺皮质癌10例，肾上腺腺瘤30例，ACTH非依赖性肾上腺增生3例)。测定CS活性的生化参数：平均血清皮质醇“日曲线”(目标150~300nmol/L)；上午9点血清皮质醇；24小时尿游离皮质醇(UFC)。共有164/195人接受了甲孕酮单药治疗。平均年龄49.6±15.7岁，平均疗程8个月(中位数3个月，3d~11.6年)。美曲酮有显著改善，首次评估至上次复习：疾控中心(91例患者，722.9 nmo1/L[26.2ug/dL]vs 348.6 nmo1/L[12.6ug/dL]；P<；0.0001)；9 AM皮质醇(123例患者，882.9 nmo1/L[32.0ug/dL]vs491.1 nmol/L[17.8ug/dL]；P<；0.0001)；和UFC(37例患者，1483nmol/24小时[537微克/24小时]对452.6 nmol/24小时[164微克/24小时]；P=0.003)。总体而言，最后一次回顾的对照：CDC、UFC、上午9点皮质醇低于331nmol/L(12.0µg/dL)、上午9点皮质醇低于正常/600nmol/L上限(21.7ug/dL)的患者分别为55%、43%、46%和76%。最终剂量的中位数：库欣病1375毫克；异位ACTH综合征1500毫克；良性肾上腺疾病750毫克；肾上腺皮质癌1250毫克。25%的患者出现不良事件，大多为轻度胃肠道不适和头晕，通常在开始或剂量增加后2周内，均可逆转。美曲拉酮是控制CS患者高皮质醇血症的短期和长期有效的治疗方法。
Cushing’s syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. This was designed as a retrospective, multicenter study. Thirteen University hospitals were studied. We studied a total of 195 patients with proven CS: 115 Cushing’s disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3). Measurements included biochemical parameters of activity of CS: mean serum cortisol “day-curve” (CDC) (target 150 –300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 µg/dL] vs 348.6 nmol/L [12.6 µg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 µg/dL] vs 491.1 nmol/L [17.8 µg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 µg/24 h] vs 452.6 nmol/24 h [164 µg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 µg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 µg/dL). Median final dose: Cushing’s disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS.