Cyclic Cushing syndrome: definitions and treatment implications

Endogenous Cushing syndrome (CS) results from hypercortisolemia caused by excess adrenocorticotropic hormone production in a pituitary adenoma or ectopic tumor, or by an adrenal tumor that directly produces excess cortisol. The diagnosis can usually be ascertained with a reasonable degree of certainty based on clinical and laboratory findings of hypercortisolism. There are patients, however, in whom the production of excess cortisol exhibits a cyclic or intermittent pattern, and, as a result, the clinical symptoms may be quite complex and varied. In these patients the hypothalamic-pituitary-adrenal axis may be normal between cycles, and dexamethasone suppression testing may produce a paradoxical response. In the present article, the authors provide a definition of cyclic Cushing syndrome, review the causes and its potential pathophysiological mechanisms, and discuss the treatment options based on a review of the available literature.