[Hepatotoxicity of a synthetic cortisol antagonist: OP'DDD (mitotane)]

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 Levels at which the drug should be withdrawn remain to be established.