Exogenous (iatrogenic) CS is common, whereas endogenous causes of CS are rare and can be broadly divided into adrenocorticotropic hormone (ACTH)-dependent (approximately 80%; Cushing’s disease (CD), ectopic ACTH secreting tumors, corticotropin-releasing hormone (CRH)-secreting tumors) and ACTH-independent (20%; adrenal tumor, carcinoma, and macronodular hyperplasia (AIMAH)). The gene discussed is CRH; the disease is Cowden syndrome 1.