Abstract
Cushing’s Syndrome (CS) is a rare disease due to chronic endogenous cortisol
secretion. In recent years, new developments have broadened the spectrum of
differential diagnosis, traditionally categorized as adrenocorticotropic hormone
(ACTH)-dependent and ACTH-independent forms. Moreover, increased awareness of
the detrimental effects of cortisol on cardiometabolic health and the risk of
cardiovascular events lead to increased diagnosis of mild forms, especially in
the context of adrenal incidentalomas.
This review provides an up-to-date narrative of the most recent literature
regarding the challenges of CS diagnosis. After the description of the
diagnostic tools available, the functional non-neoplastic hypercortisolism
(formerly known as pseudo-Cushing state) is characterized, followed by the
subtyping of the different conditions of hypercortisolism, including the
differential diagnosis of ACTH-dependent forms and the management of adrenal
hypercortisolism, with peculiar attention to the new genetic classification of
adrenal CS, mild autonomous cortisol secretion, and bilateral adrenal
adenomas.
Keywords
Cushing’s Syndrome - Cushing’s disease - ectopic ACTH secretion - diagnosis - non-neoplastic
hypercortisolism
