The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin

Helgadóttir, Hólmfríður; Metz, David C.; Yu, Yang; Rhim, Andrew D.; Bjõrnsson, Einar

doi:10.1016/j.dld.2013.09.021

Cited by 20 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our cases, pathological gastrin levels were reported only in Patient 1, mild hypergastrinemia was observed in Patient 3, while the Patient 2 was normogastrinemic. In our patients only fasting gastrin assays were obtained; however, as recently reported by Helgadottir et al [44], elevated mealstimulated circulating gastrin levels were observed in patients taking PPIs compared to controls, giving reason for an overall greater gastrin stimulation in patients taking PPI, regardless of fasting gastrin levels. Thus, one can postulate that gastrin, even when fasting levels are within the normal range, can play an important role in the proliferation of ECL-cells during PPI therapy.…”

Section: Discussionsupporting

confidence: 48%

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

Cavalcoli

Zilli

Conte

et al. 2015

Scandinavian Journal of Gastroenterology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 48%

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

Cavalcoli

Zilli

Conte

et al. 2015

Scandinavian Journal of Gastroenterology

View full text Add to dashboard Cite

show abstract

“…These results are in line with and expand on our earlier study that showed that female PPI users had significantly higher gastrin levels than did male patients both before and after meal stimulation. 10 Results from studies examining gender differences in gastrin levels in patients on PPIs have been conflicting. Wang et al 16 found among GERD patients on PPIs a nonsignificant trend for higher gastrin levels in female patients than in male patients (47 vs. 40 pM).…”

Section: Discussionmentioning

confidence: 99%

“…10 The reason for this exaggerated gastrin response in women on PPI therapy is unclear. We wanted to test the hypothesis that women with GERD on long-term PPIs are more likely than men to have a successful step-down of PPI dose due to increased sensitivity to PPIs by decreasing the dose by half.…”

mentioning

confidence: 99%

Study of Gender Differences in Proton Pump Inhibitor Dose Requirements for GERD

Helgadóttir

Metz

Lund

et al. 2017

Journal of Clinical Gastroenterology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Higher levels are seen in females and in those with atrophy of the gastric corpus due to CAG, whether auto-immune or due to Helicobacter pylori [27]. Recent studies, however, have shown that FSG levels in PPI users do not reflect the 4-or 5-fold elevations in mean serum gastrin concentrations that occur and persist after meals, particularly in females [28]. These results indicate that studies to date may have seriously underestimated ECL-cell exposure to gastrin in PPI users.…”

Section: Observations In Humansmentioning

confidence: 96%

Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?

McCarthy

2020

IJMS

View full text Add to dashboard Cite

Neuroendocrine tumors (NETs) throughout the body are the focus of much current interest. Most occur in the gastrointestinal tract and have shown a major increase in incidence over the past 30 years, roughly paralleling the world-wide increase in the use of proton pump inhibitor (PPI) drugs. The greatest rise has occurred in gastric carcinoids (g-NETs) arising from enterochromaffin-like (ECL) cells. These tumors are long known to occur in auto-immune chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome (ZES), with or without multiple endocrine neoplasia type-1 (MEN-1), but the incidences of these conditions do not appear to have increased over the same time period. Common to these disease states is persistent hypergastrinemia, generally accepted as causing g-NETs in CAG and ZES, and postulated as having similar tumorigenic effects in PPI users. In efforts to study the increase in their occurrence, g-NETs have been classified in a number of discussed ways into different grades that differ in their incidence and apparent pathogenesis. Based on a large amount of experimental data, tumorigenesis is mediated by gastrin’s effects on the CCK2R-receptor on ECL-cells that in turn leads to hyperplasia, dysplasia, and finally neoplasia. However, in all three conditions, the extent of response of ECL-cells to gastrin is modified by a number of genetic influences and other underlying risk factors, and by the duration of exposure to the hormonal influence. Data relating to trophic effects of hypergastrinemia due to PPI use in humans are reviewed and, in an attached Appendix A, all 11 reports of g-NETs that occurred in long-term PPI users in the absence of CAG or ZES are summarized. Mention of additional suspected cases reported elsewhere are also listed. Furthermore, the risk in humans may be affected by the presence of underlying conditions or genetic factors, including their PPI-metabolizer phenotype, with slow metabolizers likely at increased risk. Other problems in estimating the true incidence of g-NETs are discussed, relating to non-reporting of small tumors and failure of the Surveillance, Epidemiology, and End Results Program (SEER) and other databases, to capture small tumors or those not accorded a T1 rating. Overall, it appears likely that the true incidence of g-NETs may be seriously underestimated: the possibility that hypergastrinemia also affects tumorigenesis in additional gastrointestinal sites or in tumors in other organ systems is briefly examined. Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects.

show abstract

The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin

Cited by 20 publications

References 28 publications

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

Study of Gender Differences in Proton Pump Inhibitor Dose Requirements for GERD

Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?

Contact Info

Product

Resources

About