Ketoconazole inhibits cortisol synthesis by a direct action on the P450 cytochrome enzymes. It is generally well tolerated (400ΓÇô800mg/d), although hepatotoxicity is an occasional problem. Disseminated adrenal carcinoma responds poorly to any therapy but can sometimes be controlled by large doses (4-l0g/d) of o,p-DDD: at these doses, unpleasant side effects, such as nausea and ataxia, are common. In Cushing's disease, lower doses (1ΓÇô3g/d) may be successfully used in the medical management without side effects. The drug takes six weeks to be fully effective and often raises circulating lipid levels.
