Medical management of Cushing's disease

Cushing's disease (CD), caused by excess adrenocorticotropin secretion from tumorous pituitary corticotrophs, is associated with substantial morbidity and mortality. The primary, definitive therapy for patients with CD is selective pituitary adenomectomy, generally performed via a transsphenoidal approach. Medical therapy has an important adjunctive role in the management of patients with CD, including preoperative patient preparation in patients with severe disease, and temporizing management of hypercortisolism while awaiting the effects of radiation therapy to occur in patients who are not in remission postoperatively. Medical therapy can also be used in patients with hypercortisolism of unclear origin or in the few patients who decline or are unfit for surgery. Available medical options for patients with CD include centrally acting agents (cabergoline and pasireotide), steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane and etomidate) and a glucocorticoid receptor antagonist (mifepristone). Pasireotide and mifepristone have been recently granted regulatory approval in some countries for use in patients with CD, whereas other medications are used off label in this patient population. As clinical trials using comparator agents have not been reported, the choice between different medications is based on patient characteristics and preference. Despite impressive advances in pharmacotherapy for patients with CD, much remains to be done. The long term efficacy and safety of medical therapies for hypercortisolism need to be evaluated and the role of combination therapy must be further characterized. As the pathogenesis of CD becomes better understood at the molecular level, it is likely that novel, targeted medical therapies will be developed to treat CD.