Neuropsychiatric disorders in Cushing's syndrome

Glucocorticoids are crucial in the initiation and consolidation of the stress response. Patients with active Cushing's syndrome (CS) are exposed to excessive endogenous glucocorticoid levels. In these patients, psychopathology is often being observed. The most common co-morbid disorder is major depression, but to a lesser extent mania and anxiety disorders have also been reported. A severe clinical presentation of CS often also includes depression. Reduction of glucocorticoid synthesis or action, either with metyrapone, ketoconazole, or mifepristone, rather than treatment with antidepressant drugs, is generally successful in relieving depressive symptoms, as well as other disabling symptoms. Following successful surgical treatment of hypercortisolism, both physical and psychiatric signs and symptoms improve substantially. However, it appears that patients do not completely return to their premorbid level of functioning and persistent impairment of quality of life and cognitive function has been reported despite long-term cure. At present, it is not clear whether, and to which extent, psychopathology still affects general well-being after long-term cure of CS.