A prospective study of gastric carcinoids and enterochromaffin-like cell changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors

J Clin Endocrinol Metab. 2008 May;93(5):1582-91. doi: 10.1210/jc.2007-2279. Epub 2008 Feb 12.

Abstract

Context: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (ZES). These patients can develop proliferative changes of gastric enterochromaffin-like (ECL) cells and gastric carcinoids (ECL-cell tumors). ECL-cell changes have been extensively studied in sporadic ZES patients and can be precursor lesions of gastric carcinoids, but little is known about factors influencing their severity or development of carcinoids in MEN1/ZES patients.

Objectives: Our objective was to prospectively analyze ECL-cell changes and gastric carcinoids (ECL-cell tumors) in a large series of MEN1/ZES patients to detect risk factors and deduct clinical guidelines.

Setting and patients: Fifty-seven consecutive MEN1/ZES patients participated in this prospective study at two tertiary-care research centers.

Interventions and outcome measures: Assessment of MEN1, gastric hypersecretion, and gastroscopy with multiple biopsies was done according to a fixed protocol and tumor status. ECL-cell changes and alpha-human chorionic gonadotropin staining were assessed in each biopsy and correlated with clinical, laboratory, and MEN1 features.

Results: ECL-cell proliferative changes were universally present, advanced changes in 53% and carcinoids in 23%. Gastric nodules are common and are frequently associated with carcinoids. Patients with high fasting serum gastrin levels, long disease duration, or a strong alpha-human chorionic gonadotropin staining in a biopsy are at higher risk for an advanced ECL-cell lesion and/or gastric carcinoid.

Conclusions: Gastric carcinoids and/or advanced ECL-cell changes are frequent in MEN1/ZES patients, and therefore, regular surveillance gastroscopy with multiple routine biopsies and biopsies of all mucosal lesions are essential. Clinical/laboratory data and biopsy results can be used to identify a subgroup of MEN1/ZES patients with a significantly increased risk for developing gastric carcinoids, allowing development of better surveillance strategies.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoid Tumor / blood
  • Carcinoid Tumor / etiology*
  • Carcinoid Tumor / pathology
  • Enterochromaffin-like Cells / pathology*
  • Female
  • Gastrins / blood
  • Humans
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1 / pathology*
  • Prospective Studies
  • Risk Factors
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / pathology
  • Zollinger-Ellison Syndrome / pathology*

Substances

  • Gastrins