Recent advances in the medical treatment of Cushing’s disease

Cushing’s disease is a condition of hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. While rare, it is associated with significant morbidity and mortality, which suggests that early and aggressive intervention is required. The primary, definitive therapy for patients with Cushing’s disease in the majority of patients is pituitary surgery, generally performed via a transsphenoidal approach. However, many patients will not achieve remission or they will have recurrences. The consequences of persistent hypercortisolism are severe and, as such, early identification of those patients at risk of treatment failure is exigent. Medical management of Cushing’s disease patients plays an important role in achieving long-term remission after failed transsphenoidal surgery, while awaiting effects of radiation or before surgery to decrease the hypercortisolemia and potentially reducing perioperative complications and improving outcome. Medical therapies include centrally acting agents, adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers. Furthermore, several new agents are in clinical trials. To normalize the devastating disease effects of hypercortisolemia, it is paramount that successful patient disease management includes individualized, multidisciplinary care, with close collaboration between endocrinologists, neurosurgeons, radiation oncologists, and general surgeons. This commentary will focus on recent advances in the medical treatment of Cushing’s, with a focus on newly approved ACTH modulators and glucocorticoid receptor blockers.