Recent developments in drug therapy for Cushing's disease.

Cushing's disease (CD) is a rare endocrine disorder that is caused by an adrenocorticotropin (ACTH)-producing pituitary adenoma that chronically stimulates adrenocortical cortisol production. CD is primarily treated by transsphenoidal surgery, resulting in long-term biochemical remission in approximately 60-90% of the patients. Patients who are ineligible for surgery or have undergone unsuccessful surgery are candidates for drug therapy. Medical treatment can aim to inhibit the excess ACTH production at the level of the pituitary adenoma, to decrease adrenocortical steroidogenesis or to antagonize the effects of cortisol at the level of its receptor. In recent years, a number of studies have been published that evaluated the efficacy of medical therapy, either as monotherapy or combination therapy, in patients with CD. In particular, the effects of the somatostatin analog pasireotide and the glucocorticoid receptor antagonist mifepristone have been investigated in two large clinical trials. Moreover, the first clinical experiences with the novel steroidogenesis inhibitor LCI699 and the pituitary-directing retinoic acid have become available. Finally, an in vitro study with gefitinib, an epidermal growth factor receptor-antagonist, showed promising results that warrant further exploration. In this review, the efficacy and limitations of drugs that have been used in the treatment of CD will be discussed as well as recent developments with respect to new pituitary- and adrenal-targeting compounds.