Abstract and Introduction
Cushing's syndrome is a debilitating endocrine disorder which results from hypercortisolemia. While endogenous Cushing's syndrome can be caused by an adrenocorticotrophic hormone (ACTH)-dependent or ACTH-independent mechanism, it is most often a result of excess secretion of ACTH by a corticotroph adenoma (Cushing's disease). Untreated hypercortisolemia causes significant morbidity and increased mortality due to its metabolic effects including hypertension, osteoporosis, obesity, dyslipidemia, osteoporosis and glucose intolerance. Although primary therapy is surgical, a substantial portion of patients will go on to require second-line therapies including repeat surgery, radiotherapy or drug therapy. While medical therapy for Cushing's syndrome has been limited, several new agents are being investigated. This aim of this review is to analyze and present the available options for medical management of Cushing's syndrome as well as review potential new therapies and their role in the treatment of this disorder.
Endogenous Cushing's syndrome is a debilitating endocrine disorder which results from excess circulating cortisol. Eighty percent of the cases are a result of excess adrenocorticotrophic hormone (ACTH) secretion, usually by a corticotroph pituitary adenoma, also called Cushing's disease. Other causes of ACTH-dependent Cushing's syndrome include extrapituitary tumors that secrete ACTH (ectopic Cushing's syndrome) and, rarely, corticotroph-releasing hormone-secreting tumors. Twenty percent of the patients with endogenous Cushing's syndrome will have ACTH-independent Cushing's syndrome caused by an adrenocortical tumor or adrenal hyperplasia. While a rare disease with an estimated incidence of two to three cases per million population per year, the metabolic effects of hypercortisolemia may result in hyperglycemia, osteoporosis, hypertension, dyslipidemia, obesity, muscle weakness, depression, hirsutism, acne, cognitive impairment, menstrual disturbances and fatigue. These effects cause significant morbidity and decreased quality of life. The overall mortality in patients with active Cushing's syndrome may be up to four-times higher than the general population.