As expected, under long-term RU486 administration some clinical peripheral features of the Cushing’s syndrome are ameliorated such as hyperglycemia (15); as expected also, in the patients with Cushing’s disease, the hypothalamic–pituitary–adrenal axis is stimulated (by the “apparent” cortisol deprivation) and ACTH is acutely and/or chronically increased further with plasma levels raising up ca. three times above their baseline initial values (16, 17). The gene discussed is POMC; the disease is Cushing syndrome due to macronodular adrenal hyperplasia.