HRH2 and Zollinger-Ellison syndrome: PPIs treatment is a major problem in the diagnosis of ZES because not only does its use induce hypergastrinemia in non-ZES patients, therefore mimicking ZES, but because of their potency/long-duration of action, in contrast to H2R antagonists (nizatidine, famotidine cimetidine, ranitidine); PPIs control symptoms in most ZES patients at conventional doses used in the treatment of idiopathic PUD/GERD or they are frequently used for UGI symptoms in non-ZES patients [9,59,88,92,217,218,219,220,221].