Vitamin B12 Deficiency with Dyspepsia
A 58-year-old woman has 3 months of epigastric pain with intermittent vomiting and 5 kg weight loss. Hemoglobin is 13.2 g/dL, MCV 92 fL, serum vitamin B12 is 90 pg/mL, and serum folate is normal. She has no diarrhea, takes no metformin, and drinks no alcohol. What is the most appropriate next investigation?
- A.Colonoscopy with terminal ileal biopsy
- B.Small bowel barium follow-through
- C.Upper endoscopy with gastric biopsyCorrect
- D.Serum anti-intrinsic factor antibody
Explanation
Low vitamin B12 with normal folate localises the problem to the stomach or the terminal ileum, and the accompanying epigastric pain, vomiting and 5 kg weight loss are alarm features that make structural gastric disease the priority. Upper endoscopy with biopsies of the body and antrum answers both questions at once: it explains the dyspepsia and it establishes the mechanism of the deficiency by demonstrating autoimmune atrophic gastritis, intestinal metaplasia, Helicobacter pylori infection or gastric carcinoma. Autoimmune atrophic gastritis destroys parietal cells, removing intrinsic factor and gastric acid, and carries an increased risk of gastric neuroendocrine tumours and adenocarcinoma, so American Gastroenterological Association guidance recommends a baseline endoscopy with mapped biopsies whenever it is suspected. A normal hemoglobin and a normal MCV do not exclude B12 deficiency, because megaloblastic change appears late and can be masked by coexisting iron deficiency. Colonoscopy, even with ileal intubation, is directed at lower gastrointestinal bleeding or iron deficiency and does not address alarm dyspepsia. Barium follow-through is reserved for suspected Crohn disease or a previous ileal resection, neither of which is suggested in a patient with no diarrhea. Anti-intrinsic factor antibody is highly specific but only about half sensitive, so a negative result would not exclude pernicious anemia and a positive result would not exclude gastric cancer. Serology may follow endoscopy, but it never substitutes for histology in a symptomatic patient with weight loss.
Why each option
- A.
- Colonoscopy with ileal biopsy targets lower gastrointestinal bleeding or Crohn disease and does not address epigastric pain, vomiting and weight loss.
- B.
- Small bowel imaging is reserved for suspected terminal ileal disease such as Crohn disease, which this presentation does not suggest.
- C.
- Correct. Endoscopy with gastric biopsy explains the dyspepsia and identifies atrophic gastritis, Helicobacter pylori or gastric malignancy as the cause of B12 deficiency.
- D.
- Anti-intrinsic factor antibody is specific but insensitive, and a result either way leaves gastric malignancy unexcluded in a patient with alarm features.
Reference: AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis, Gastroenterology, 2021; UpToDate 2025, Clinical manifestations and diagnosis of vitamin B12 and folate deficiency
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