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Last reviewed: 28 Oct 2023
Last updated: 29 Dec 2022



History and exam

Other diagnostic factors

  • age >60 years
  • female sex
  • autoimmune disorders
  • weakness
  • lethargy
  • decreased exercise tolerance
  • skin and conjunctival pallor
  • paresthesias and difficulty ambulating
  • nutritional deficiency (cobalamin, iron, calcium, vitamin D)
  • enteric infection
  • memory loss, irritability, depression, and dementia
  • ataxia, shuffling gait, decreased position sense, decreased vibration sense
  • pale, smooth, and glossy tongue
  • koilonychia
Other diagnostic factors

Risk factors

  • autoimmune disorders
  • age >60 years
  • Helicobacter pylori infection
  • prior gastric surgery
  • hypergastrinemia
  • gastric carcinoid
More risk factors

Diagnostic investigations

1st investigations to order

  • hemoglobin
  • biopsy of corpus and/or fundus of stomach
  • intragastric pH
More 1st investigations to order

Investigations to consider

  • serum gastrin
  • gastric acid secretory test (gastric analysis)
  • parietal cell antibodies
  • intrinsic factor antibodies
  • diagnostic tests for Helicobacter pylori infection
More investigations to consider

Emerging tests

  • serum pepsinogen I and II (PGI and PGII)

Treatment algorithm


all patients



Mitchell L. Schubert, MD
Mitchell L. Schubert

Professor of Medicine and Physiology

Virginia Commonwealth University Health System

Chief of Gastroenterology

McGuire VAMC




MLS is an author of several studies referenced in this topic.

Joseph Spataro, MD
Joseph Spataro

Academic Fellow

Division of Gastroenterology, Hepatology, and Nutrition

Virginia Commonwealth University Health System




JS declares that he has no competing interests.

Hamzeh Saraireh, MD
Hamzeh Saraireh

Academic Fellow

Division of Gastroenterology, Hepatology, and Nutrition

Virginia Commonwealth University Health System




HS declares that he is the author of one study referenced in this topic.


Dr Mitchell L. Schubert, Dr Joseph Spataro, and Dr Hamzeh Saraireh would like to gratefully acknowledge Dr Juan Diego Baltodano, a previous contributor to this topic.


JDB declares that he has no competing interests.

Peer reviewers

Joseph Pisegna, MD

Professor of Medicine

David Geffen School of Medicine at UCLA

Los Angeles



JP declares that he has no competing interests.

Heinz F. Hammer, MD

Associate Professor of Gastroenterology and Internal Medicine

Medical University of Graz

Attending Gastroenterologist

University Hospitals Graz



HFH has been reimbursed by AstraZeneca, Nycomed, and Janssen, the manufacturers of proton-pump inhibitors, for attending several conferences and speaking, and has been paid by AstraZeneca for running educational programs.

  • Differentials

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  • Guidelines

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