Glucose metabolism abnormalities in Cushing's syndrome: from molecular basis to clinical management

An impaired glucose metabolism, which often leads to the onset of diabetes mellitus (DM), is a common complication of chronic exposure to exogenous and endogenous glucocorticoid (GC) excess, and plays an important part in contributing to morbidity and mortality in patients with Cushing's syndrome (CS).This article reviews the pathogenesis, epidemiology, diagnosis and management of changes in glucose metabolism associated with hypercortisolism, addressing both the pathophysiological aspects and the clinical and therapeutic implications. Chronic hypercortisolism may have pleiotropic effects on all major peripheral tissues governing glucose homeostasis. Adding further complexity, both genomic and non-genomic mechanisms are directly induced by glucocorticoids (GCs) in a context-specific and cell/organ-dependent manner. In this paper, the discussion focuses on the established and potential pathological molecular mechanisms induced by chronically excessive circulating levels of GCs, affecting glucose homeostasis in various tissues.The management of patients with CS and DM includes treating their hyperglycemia and correcting their GC excess. The effects on glycemic control of various medical therapies for CS are reviewed in this paper. The association between DM and subclinical CS, and the role of screening for CS in diabetic patients are also discussed.