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Related Experiment Videos

The gastrin hypothesis. Implications for antisecretory drug selection.

W E Karnes1, J H Walsh

  • 1Division of Gastroenterology, UCLA.

Journal of Clinical Gastroenterology
|January 1, 1990
PubMed
Summary

New potent acid reducers like omeprazole offer effective acid-peptic disease control. While concerns exist about carcinoid tumors due to prolonged acid suppression, careful dosing may mitigate risks in humans.

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Area of Science:

  • Gastroenterology
  • Pharmacology
  • Oncology

Background:

  • Potent acid secretion inhibitors, like proton pump inhibitors (PPIs), are increasingly used for acid-peptic diseases.
  • Concerns regarding the long-term safety of profound acid suppression have been raised.
  • Rodent studies link lifelong acid inhibition to enterochromaffin-like (ECL) cell carcinoid tumors.

Purpose of the Study:

  • To evaluate the potential risk of ECL cell carcinoid tumors in humans with long-term use of potent acid inhibitors.
  • To explore the role of hypergastrinemia in the development of these tumors.
  • To assess strategies for minimizing risks associated with these medications.

Main Methods:

  • Review of existing literature on acid secretion inhibitors, gastrin, and ECL cell tumors.

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  • Analysis of animal models demonstrating carcinoid tumor development.
  • Examination of human hypergastrinemic states and their association with carcinoid tumors.

    • Main Results:

    • Profound, lifelong acid inhibition in rats is associated with ECL cell carcinoid tumors, linked to elevated gastrin levels.
    • Human conditions with hypergastrinemia (e.g., Zollinger-Ellison syndrome) show an increased risk of ECL cell carcinoid tumors.
    • No human cases of carcinoid tumors have been definitively linked to omeprazole use.

    Conclusions:

    • While animal data raise concerns, human susceptibility to PPI-induced carcinoid tumors remains unproven.
    • Avoiding achlorhydric doses can prevent significant hypergastrinemia while maintaining treatment efficacy.
    • Careful dosing strategies are recommended to minimize potential risks of ECL cell carcinoid tumors with long-term PPI use.