The effect of ketoconazole in pre-operative treatment in Cushing's syndrome: Three cases report

Ketoconazole is an orally active imidazole derivative that is an effective therapeutic drug in the treatment of mycotic infection. The development of gynecomastia in male patients treated with ketoconazole has led to investigation of its potent inhibitory effect on adrenal steroidogenesis. In this study, we present our preliminary experience using high dose ketoconazole, which was used safely as a palliative treatment in 3 patients with Cushing's syndrome prior to surgery. The 24-hour urinary free cortisol excretion was decreased by more than 52% in 1 to 2 days and fell to within normal limits of less than 120 μg by the 1st day, 2nd day or 15th day in these 3 patients. Cushing's syndrome was either adrenocorticotropin-dependent or -independent during treatment. In case 3, the plasma adrenocorticotropin level was unchanged during treatment in the first week, despite marked reductions in plasma and 24-hour urinary free cortisol levels. The most significant improvement of clinical symptoms was that the patients could sleep much more comfortably at night following the suppression of hypercortisolism by ketoconazole. Monitoring of liver function and addition of dexamethasone are recommended to prevent the possibility of reversible adverse effects such as severe hepatic injury and adrenal insufficiency or even crisis.