Oral agents with established efficacy in Cushing’s syndrome are metyrapone and ketoconazole.
Metyrapone inhibits cortisol synthesis at the level of 11 beta-hydroxylase , whereas the antimycotic drug ketoconazole inhibits the early steps of steroidogenesis. Typical starting doses are 500 mg/tid for metyrapone (maximum dose, 6 g) and 200 mg/tid for ketoconazole (maximum dose, 1200 mg).
Mitotane , a derivative of the insecticide o,p’DDD, is an adrenolytic agent that is also effective for reducing cortisol. Because of its side effect profile, it is most commonly used in the context of adrenocortical carcinoma, but low-dose treatment (500–1000 mg per day) has also been used in benign Cushing’s.
In severe cases of cortisol excess, etomidate can be used to lower cortisol. It is administered by continuous IV infusion in low, nonanesthetic doses.