Therapeutic strategies for Cushing's syndrome: An update

ntroduction: Endogenous Cushing's syndrome (CS) is a severe clinical condition caused by excess cortisol secretion. The treatment goals (with surgery, radiotherapy or medical therapy) are to normalize cortisol levels, reverse the clinical symptoms and remove the secreting neoplasm. Areas covered: Medical treatments are increasingly used in CS, especially when surgery fails or is not indicated, or while waiting for radiotherapy to take effect. This review summarizes the different medical approaches for treating CS (adrenal- or pituitary-directed drugs, glucocorticoid receptor antagonist), alone or in combination. Expert opinion: Adrenal steroidogenesis inhibitors have been the mainstay of medical treatment for CS: the most used are ketoconazole (or fluconazole), which inhibits adrenal steroidogenic enzymatic activities; metyrapone and LCI699 that inhibit 11 beta-hydroxylase (the latter is still an experimental compound); mitotane, used in adrenocortical carcinoma. The available glucocorticoid receptor antagonist is mifepristone, recently approved for use in controlling hyperglycemia secondary to hypercortisolism. There has recently been a lot of interest in using agents directly targeting the pituitary corticotroph cells to reduce Adreno Cortico Tropic Hormone secretion and, if possible, control the volume of pituitary adenomas. This is because corticotroph cells contain dopamine receptors (targets of bromocriptine and cabergoline), retinoic acid receptors, PPAR-gamma or somatostatin receptors, the target of the first drug developed and approved for Cushing's disease (pasireotide).