Possible, probable, and certain hypercortisolism: A continuum in the risk of comorbidity

Hypercortisolism may be considered as a continuum in terms of both hormonal and cardiometabolic abnormalities. It ranges from cases with "normal" hormonal profile and low to intermediate risk of comorbidity to florid cases with clear clinical and hormonal evidence of glucocorticoid excess and clearly increased cardiometabolic risk. Even in patients with nonfunctioning adrenal incidentaloma (NFAI), defined as adrenal incidentaloma with normal results on the currently available hormonal test for evaluation of hypercortisolism, cardiometabolic and mortality risk is higher than in the general population without adrenal lesions. Mild hypercortisolism or autonomous cortisol secretion (ACS) is a term used for patients with adrenal incidentaloma and pathological dexamethasone suppression test (DST) results, but without specific clinical signs of hypercortisolism. It is widely known that this condition is linked to higher prevalence of several cardiometabolic comorbidities, including diabetes, hypertension, osteoporosis and metabolic syndrome, than in patients with NFAI or without adrenal tumor. In case of overt Cushing's syndrome, cardiovascular risk is extremely high, and standard mortality ratio is high, cardiovascular disease being the leading cause of death. The present review summarizes the current evidence for a detrimental cardiometabolic profile in patients with possible (NFAI), probable (ACS) and certain hypercortisolism (overt Cushing's syndrome).