Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France.
Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France
Eur J Endocrinol. 2015 Apr;172(4):473-81. doi: 10.1530/EJE-14-0913. Epub 2015 Jan 26.
Severe Cushing's syndrome elicited by ectopic ACTH syndrome (EAS) or adrenal carcinoma (ACC) can threaten life in the short term. The effectiveness of oral administration of the inhibitors of steroidogenesis ketoconazole and metyrapone in this situation is poorly described.
To report the short-term effectiveness and tolerability of metyrapone and ketoconazole elicited either by EAS or by ACC in patients exhibiting severe hypercortisolism.
Retrospective analysis of data obtained for patients with urinary free cortisol (UFC) level estimated to be fivefold the upper limit of the normal range (ULN).
A total of 14 patients with EAS and eight with ACC treated in two tertiary-care university hospitals.
Metyrapone and ketoconazole treatment in combination (along with symptomatic treatments for co-morbidities).
Evolution of clinically relevant endpoints (blood pressure, kalaemia and glycaemia) and biological intensity of hypercortisolism 1 week and 1 month after starting steroidogenesis inhibition.
After 1 week of treatment, median UFC fell from 40.0 to 3.2 ULN and from 16.0 to 1.0 ULN in patients with EAS and ACC respectively. Median UFC after 1 month of treatment was 0.5 and 1.0 ULN in patients with EAS and ACC respectively and UFC values were normal in 73 and 86% of patients respectively. Clinical status improved dramatically along with kalaemia, glycaemia and blood pressure, allowing a decrease in the relevant treatments.Side effects were minimal and only two patients (one EAS and one ACC) experienced plasma transaminase elevations necessitating ketoconazole withdrawal.
Metyrapone-ketoconazole combination therapy is well tolerated and provides rapid control of endocrine cancer-related life-threatening hypercortisolism.
异位 ACTH 综合征（EAS）或肾上腺皮质癌（ACC）引起的严重库欣综合征短期内可能危及生命。目前对口服甾体生成抑制剂酮康唑和米托坦在这种情况下的疗效描述甚少。
报告米托坦和酮康唑治疗 EAS 或 ACC 引起的严重皮质醇增多症患者的短期疗效和耐受性。
对尿游离皮质醇（UFC）水平估计为正常范围上限（ULN）的 5 倍的患者数据进行回顾性分析。
在两家三级大学医院共治疗了 14 例 EAS 患者和 8 例 ACC 患者。
米托坦和酮康唑联合治疗（同时进行合并症的对症治疗）。
开始抑制甾体生成后 1 周和 1 个月时与临床相关的终点（血压、血钾和血糖）和皮质醇增多症的生物学强度的变化。
治疗 1 周后，EAS 和 ACC 患者的 UFC 中位数分别从 40.0 降至 3.2 ULN 和从 16.0 降至 1.0 ULN。治疗 1 个月后的 UFC 中位数分别为 0.5 和 1.0 ULN，分别有 73%和 86%的患者 UFC 值正常。临床状况显著改善，同时血钾、血糖和血压也得到改善，相关治疗得以减少。副作用极小，只有 2 名患者（1 例 EAS 和 1 例 ACC）出现血浆转氨酶升高，需要停用酮康唑。
米托坦-酮康唑联合治疗耐受性良好，可迅速控制与内分泌肿瘤相关的危及生命的皮质醇增多症。
