Neuman O, Bruckert E, Chadarevian R, Jacob N, Turpin G
Service d'Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, 83 boulevard de l'Hôpital, 75013 Paris, France.
Therapie. 2001 Nov-Dec;56(6):793-7.
The adrenolytic agent, Op'DDD (Mitotane) has been employed for almost 50 years for treatment of Cushing's syndrome. Despite clinical observations of elevation of hepatic enzymes encountered in patients taking the drug, there are few published data regarding the frequency, time course and factors that might influence hepatic toxicity of Mitotane. We analysed 10 patients consecutively treated with Mitotane for Cushing's syndrome. We measured hepatic transaminase and gamma glutamyl transferase before, during and after treatment. The study population included 6 women and 4 males, with a mean age of 41 years. Seven patients presented Cushing's disease while two had adrenal tumours and one had an undetermined origin of Cushing's syndrome. After a progressive increase, patients were being treated with a mean dosage of 9 g per day. All patients had elevation of either GGT or ALAT and all but one had elevation of transaminase (the maximum increase was sixfold the basal value). The only variable correlated with hepatic increase was the body mass index. In contrast, the severity of the disease, alcohol intake, and other biological characteristics were not correlated with transaminase elevations. We conclude that transaminase increase is encountered in the vast majority of patients treated with Mitotane. Levels at which the drug should be withdrawn remain to be established.
肾上腺溶解剂双氯苯二氯乙烷（米托坦）已用于治疗库欣综合征近50年。尽管临床观察到服用该药的患者肝酶升高，但关于米托坦肝毒性的发生频率、时间进程及可能影响因素的公开数据很少。我们分析了10例连续接受米托坦治疗库欣综合征的患者。我们在治疗前、治疗期间和治疗后测量了肝转氨酶和γ-谷氨酰转移酶。研究人群包括6名女性和4名男性，平均年龄41岁。7例患者患有库欣病，2例患有肾上腺肿瘤，1例库欣综合征病因不明。在逐步增加剂量后，患者平均每天接受9克的治疗。所有患者的γ-谷氨酰转移酶（GGT）或丙氨酸转氨酶（ALAT）均升高，除1例患者外，所有患者的转氨酶均升高（最大增幅为基础值的6倍）。与肝脏指标升高相关的唯一变量是体重指数。相比之下，疾病严重程度、酒精摄入量及其他生物学特征与转氨酶升高无关。我们得出结论，在绝大多数接受米托坦治疗的患者中都会出现转氨酶升高。停药的阈值仍有待确定。
