Diagnosis of Zollinger–Ellison Syndrome in the Era of Ppis, Faulty Gastrin Assays, Sensitive Imaging and Limited Access to Acid Secretory Testing

Abstract

In recent years the diagnosis of Zollinger-Ellison syndrome (ZES) has become increasingly controversial with several new approaches and criteria proposed, differing from the classical biochemical criterion of inappropriate hypergastrinemia (i.e., hypergastrinemia in the presence of hyperchlorhydria) (Table 1). These changes have come about because of the difficulty and potential dangers of stopping proton pump inhibitors (PPIs) for gastric acid analysis; the recognition than many of the current assays used to assess gastrin concentrations are unreliable; the development of sensitive imaging modalities that detect neuroendocrine tumors (NETs) including an increasing number of the primary gastrinomas; the increased use of percutaneous or endoscopic ultrasound (EUS)-directed biopsies/cytology and the general lack of availability of acid secretory testing. In this article we will discuss the basis for these controversies, review the proposed changes in diagnostic approaches and make recommendations for supporting the diagnosis of ZES in the modern era.

Prognostic factors and survival in MEN1 patients with gastrinomas: Results from the DutchMEN study group (DMSG)

“…14,15 Gastrinoma diagnosis frequently differs from these criteria, because of the lack of gastric pH measurement, the unavailability of secretin testing and the use of immunohistochemistry and imaging as alternatives. 26 In daily clinical practice of the 14,15 Although 52% had a pNET at the moment of gastrinoma diagnosis, only 19% of all patients in this cohort had pNETs >2.0 cm on cross-sectional imaging. Especially, in the coexistence of hypergastrinemia and pNETs ≥2.0 cm, the optimal surgical strategy is hard to establish.…”

“…Current guidelines recommend the combination of hypergastrinemia and basal gastric acid hypersecretion (pH < 2) . Gastrinoma diagnosis frequently differs from these criteria, because of the lack of gastric pH measurement, the unavailability of secretin testing and the use of immunohistochemistry and imaging as alternatives . In daily clinical practice of the DMSG, gastrinoma diagnosis was complicated by the unavailability of stimulation tests, no routine measurements of gastric pH and widespread use of PPI.…”

De novo Gastrinoma: A Case Report

“…The most interesting aspect of this case is related to the appearance of a de novo gastrinoma 25 years after the first episode. Although frequent, as more than 50% of all surgically treated patients relapse, it occurs mostly within the first 2 years [7]. The risk factors are not well known, but size, histological grade, and neural invasion seem to be implicated.…”

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d’étude des Tumeurs Endocrines) Study

“…The diagnosis of insulinoma was based on the presence of hypoglycemic symptoms associated with low plasma glucose concentrations and abnormally high serum insulin or C-peptide [ 14 ]. Zollinger–Ellison syndrome criteria were the presence of continuous specific clinical symptoms associated with ZES features found on endoscopy, an inability to discontinue high-dose proton pump inhibitors, and at least 2 out of the 4 National Institute of Health (NIH) criteria and a histological confirmation of gastrinoma [ 15 , 16 ]. A diagnosis of VIPoma was confirmed in patients with the association of watery diarrhea and a high serum vasoactive intestinal peptide level.…”