Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The gene discussed is POMC; the disease is Cushing syndrome due to macronodular adrenal hyperplasia.