Glucose and lipid metabolism abnormalities in Cushing's syndrome

Prolonged excess of glucocorticoids (GCs) has adverse systemic effects leading to significant morbidities and an increase in mortality. Metabolic alterations associated with the high level of the GCs are key risk factors for the poor outcome. These include GCs causing excess gluconeogenesis via upregulation of key enzymes in the liver, a reduction of insulin sensitivity in skeletal muscle, liver and adipose tissue by inhibiting the insulin receptor signalling pathway, and inhibition of insulin secretion in beta cells leading to dysregulated glucose metabolism. In addition, chronic GC exposure leads to an increase in visceral adipose tissue, as well as an increase in lipolysis resulting in higher circulating free fatty acid levels and in ectopic fat deposition. Remission of hypercortisolism improves these metabolic changes, but very often does not result in full resolution of the abnormalities. Therefore, long-term monitoring of metabolic variables is needed even after the resolution of the excess GC levels.