The Relationship of Gastrinoma in MEN 1 to Helicobacter pylori infection

Abstract

Context Helicobacter pylori (H. pylori) and Multiple Endocrine Neoplasia Type 1 (MEN 1) are risk factors for hypergastrinaemia. Gastrin-secreting neoplasms of the foregut mucosa are both a source of, and potentially stimulated by, hypergastrinaemia. Objective To determine the relationship between H. pylori exposure and the prevalence and severity of hypergastrinaemia in patients with MEN 1. Design setting & patients Cross-sectional analysis of patients with a common MEN1 gene mutation managed at a tertiary referral hospital that underwent fasting serum gastrin and H. pylori serum IgG measurement. Intervention H. pylori IgG and serum gastrin concentration, determined via immunoassay. Main outcome measures The prevalence and severity of hypergastrinaemia, and its relationship to past H. pylori exposure. Results Thirty four of 95 (36%) patients were H. pylori IgG seropositive. H. pylori seropositive patients were significantly more likely to exhibit hypergastrinaemia compared to seronegative patients (RR 1.72, p=0.023). H. pylori exposure also predicted severe hypergastrinaemia (RR 3.52, p=0.026 and RR 9.37, p=0.031 for patients with gastrin ≥x4 and ≥x8 the upper limit of normal [ULN], respectively). Gastrin concentrations ≥x10 ULN occurred exclusively in H. pylori seropositive patients (0/61 vs 6/34, p=0.001). Serum gastrin and alpha subunit were positively associated in H. pylori-exposed (β=0.69, p=0.001), but not in H. pylori-unexposed patients. Conclusion Past H. pylori exposure was associated with increased prevalence and severity of hypergastrinaemia in MEN 1 patients. Past H. pylori-related hypergastrinaemia may contribute to the pathogenesis of ongoing gastrin hypersecretion by susceptible foregut neuroendocrine tissues.