What is the role of medical therapy in adrenal-dependent Cushing's syndrome?

Medical therapy to control hypercortisolism in adrenal Cushing's syndrome is currently not the first-line therapy. However, in many clinical scenarios like pre-surgical treatment, in patients who are not suitable candidates for surgery or in patients with bilateral hyperplasia, medical therapy can be important representing the only viable treatment option. Adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers have been used for many years: metyrapone, ketoconazole and mifepristone are in current use and effective. Mitotane can be used as well but is considered second-line therapy because of its high toxicity. Etomidate has a special position as emergency medication in severe hypercortisolism. New drugs are tested in prospective trials (levoketoconazole, osilidrostat and relacorilant) and might become effective alternatives to common drugs. Oher drugs - adrenal steroidogenesis inhibitors as well as glucocorticoid receptor antagonists - are currently tested in vitro.