ISL1 that plays a crucial role in embryogenesis and differentiation of pancreatic beta cells and is frequently expressed in PanNETs [1] but also in duodenal NETs (83%), rectal NETs (75%) [58], and middle ear NETs (100%) [2] was found to be expressed in all non-functioning RenNETs, but not in the Cushing syndrome cases. This evidence concerns the gene ISL1 and Cushing syndrome due to macronodular adrenal hyperplasia.