Recent progress in pathophysiology of cortisol-producing adrenal tumor.

Abstract

This review summarizes recent basic and clinical advances in cortisol-producing adrenal tumors, including Cushing's syndrome (CS) and mild autonomous cortisol secretion (MACS). Recent clinical reports on the epidemiology and diagnostic challenges of CS and MACS are presented. The review highlights recent progress in understanding the molecular pathogenesis of adrenal cortisol-producing tumors. A major recent finding is the discovery of loss-of-function mutation in KDM1A as the underlying cause of the long-standing mystery of diet-dependent CS in primary bilateral macronodular adrenal hyperplasia (PBMAH). Furthermore, the recent clarification of the molecular basis of cortisol-producing adenomas (CPAs) has deepened our understanding of the functional differences in the autonomicity of CPAs between overt CS and MACS. These findings made us reconsider the categorization of adrenal tumors, including non-functioning adrenal tumors (NFATs). Finally, we reviewed the rarely discussed but critical condition of immune reconstitution inflammatory syndrome (IRIS) following CS treatment, including a case from our own experience. IRIS should be kept in mind when initiating treatment for CS patients with extremely high serum cortisol levels.