Ketoconazole in Cushing's Disease: Is It Worth a Try?
Ketoconazole in Cushing's Disease: Is It Worth a Try?
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DOI：
10.1210/jc.2013-3628
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发表时间：
2014-05-01
影响因子：
5.8
通讯作者：
Brue, Thierry
中科院分区：
文献类型：
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作者：
Castinetti, Frederic;Guignat, Laurence;Brue, Thierry
背景资料：由于潜在的肝毒性，欧洲药品管理局和食品药品监督管理局最近警告酮康唑的使用受到质疑。然而，酮康唑经常被用作降低循环皮质醇水平的药物。尽管功效有限或副作用明显，但最近几种药物已被批准用于治疗库欣病（CD）。酮康唑已在全球范围内使用了30多年的CD，但在缺乏大规模的研究，其疗效和耐受性仍在辩论中Patients and methods：我们进行了一项法国回顾性多中心研究审查数据从患者的酮康唑作为单一药物治疗CD，目的是澄清疗效和耐受性，以更好地确定效益/风险平衡。本研究纳入了200例患者的数据。在最后一次随访时，49.3%的患者尿游离皮质醇（UFC）水平正常，25.6%的患者至少下降50%，25.4%的患者UFC水平不变。酮康唑的中位最终剂量为600 mg/d。40例患者（20%）接受酮康唑作为术前治疗;这些患者中有40%-50%的患者显示高血压、低钾血症和糖尿病改善，48.7%的患者术前UFC正常。总体而言，41例患者（20.5%）因耐受性差而停止治疗。分别在13.5%和2.5%的患者中观察到肝酶轻度（5 N，上级至5倍正常值）升高。结论：酮康唑是一种有效的药物，副作用可以接受。应在密切的肝酶监测下使用。肝毒性通常是轻度的，停药后即可消退。
Background: The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However, ketoconazole is frequently used as a drug to lower circulating cortisol levels. Several pharmacological agents have recently been approved for the treatment of Cushing's disease(CD) despite limited efficacy or significant side effects. Ketoconazole has been used worldwide for more than 30 years in CD, but in the absence of a large-scale study, its efficacy and tolerance are still under debate.Patients and methods: We conducted a French retrospective multicenter study reviewing data from patients treated by ketoconazole as a single agent for CD, with the aim of clarifying efficacy and tolerance to better determine the benefit/risk balance.Results: Data from 200 patients were included in this study. At the last follow-up, 49.3% of patients had normal urinary free cortisol (UFC) levels, 25.6% had at least a 50% decrease, and 25.4% had unchanged UFC levels. The median final dose of ketoconazole was 600 mg/d. Forty patients (20%) received ketoconazole as a presurgical treatment; 40% to 50% of these patients showed improvement of hypertension, hypokalemia, and diabetes, and 48.7% had normal UFC before surgery. Overall, 41 patients (20.5%) stopped the treatment due to poor tolerance. Mild (5N, superior to 5-fold normal values) increases in liver enzymes were observed in 13.5% and 2.5% of patients, respectively. No fatal hepatitis was observed.Conclusions: Ketoconazole is an effective drug with acceptable side effects. It should be used under close liver enzyme monitoring. Hepatotoxicity is usually mild and resolves after drug withdrawal.