In ACTH-dependent CS, when other treatment modalities are not suitable, available or effective [66, 67] bilateral adrenalectomy provides an immediate resolution of hypercortisolism, but it also leads to iatrogenic, chronic adrenal insufficiency, which is associated with higher morbidity and mortality compared to healthy subjects, due to the high risk of infections [72–74]. This evidence concerns the gene POMC and Cowden syndrome 1.