Potential differences between males and females could for example be based on: (1) Different concentrations of corticosteroid binding globulin (CBG) (19), (2) Different ACTH secretion and cortisol production rate (20, 21), (3) Different interaction between corticosteroids and the gonadotroph axis, and (4) Different disease entity of Cushing's syndrome. This evidence concerns the gene POMC and Cushing syndrome due to macronodular adrenal hyperplasia.