On the other hand, non-cancer-related Cushing syndrome involves positive adenomas for various somatic mutations of PRKACA, PRKAR1A, PRKACB, GNAS, PDE11A and PDE8B (cyclic AMP signalling pathways) genes and primary bilateral macronodular adrenal hyperplasia (PBMAH) underlying inactivating mutations of thegermline ARMC5 gene (20–25% of all PBMAH cases), menin, GNAS, as well as the somatic KDM1A gene (identified in >90% of PBMAH with food-dependent Cushing syndrome) [138,139,140,141,142]. This evidence concerns the gene PDE8B and Cushing syndrome due to macronodular adrenal hyperplasia.