Cushing's disease is the most frequent aetiology of Cushing's syndrome, and the combination of clinical factors including reproductive age, female sex, slow onset of symptoms over several years, moderate increase in UFC (<4× ULN) and ACTH (plasma <100 pg/mL) have a high predictive value of Cushing's disease. The gene discussed is POMC; the disease is Cushing syndrome due to macronodular adrenal hyperplasia.