What is the appropriate diagnostic approach for a middle-aged to older adult patient presenting with anemia and weight loss without evidence of bleeding?

Anemia Workup with Weight Loss and No Bleeding

In a patient presenting with anemia and weight loss without overt bleeding, you must urgently pursue bidirectional endoscopy (gastroscopy and colonoscopy) as the first-line investigation, as approximately one-third of such patients harbor underlying gastrointestinal malignancy or other significant pathology. 1

Initial Laboratory Confirmation

Before proceeding with invasive testing, confirm iron deficiency with appropriate studies:

• Measure serum ferritin as the single most useful marker – a level <45 μg/dL in the setting of anemia confirms iron deficiency 1
• Check transferrin saturation if ferritin is equivocal or if inflammatory conditions may falsely elevate ferritin (ferritin 45-100 μg/dL with transferrin saturation <30% suggests iron deficiency) 1, 2
• The combination of anemia plus weight loss is a red flag that mandates urgent investigation regardless of ferritin level 3

Mandatory Endoscopic Evaluation

Perform both gastroscopy and colonoscopy as first-line investigations in all men and postmenopausal women with unexplained iron deficiency anemia, particularly when accompanied by weight loss: 1

Upper Endoscopy Must Include:

• Small bowel biopsies (duodenal) to screen for celiac disease, which accounts for 3-5% of iron deficiency anemia cases 1
• Careful examination for Cameron's erosions in hiatal hernias, gastric antral vascular ectasia (GAVE), angiodysplasias, and peptic ulcers 2
• Gastric body and antral biopsies to evaluate for atrophic gastritis and Helicobacter pylori, as non-bleeding causes account for 51% of cases 4

Lower Endoscopy:

• Colonoscopy is preferred over CT colonography as the initial test 1
• Colon cancer is 7 times more common than upper GI cancer in this population 3
• Look for colonic vascular ectasias, polyps, and inflammatory bowel disease 4

Critical Diagnostic Considerations

The weight loss component of this presentation significantly elevates concern for malignancy:

• Upper GI cancers (gastric) and colon cancers commonly present with iron deficiency anemia and weight loss before other symptoms develop 1
• Approximately 85% of patients without obvious bleeding sources will have an identifiable cause on bidirectional endoscopy 4
• Diseases not associated with bleeding (atrophic gastritis, celiac disease, H. pylori gastritis) account for over half of cases and are frequently overlooked 4

Additional Initial Testing

Perform these tests concurrently with endoscopy planning:

• Serological celiac screening with tissue transglutaminase antibody (IgA) plus total IgA level 1
• Urinalysis or urine microscopy to exclude urinary blood loss 1
• Review medications, particularly NSAIDs and anticoagulants 1

When Bidirectional Endoscopy Is Negative

If gastroscopy and colonoscopy reveal no source and weight loss persists:

• Proceed with capsule endoscopy to evaluate the small bowel, as angiectasias account for up to 80% of obscure bleeding 2
• Consider CT or MRI enterography when weight loss, abdominal pain, or elevated inflammatory markers suggest small bowel malignancy or Crohn's disease 3
• Deep enteroscopy with distal attachment should be performed if small bowel angioectasias are suspected 1

Common Pitfalls to Avoid

• Do not attribute anemia solely to "anemia of chronic disease" without excluding GI pathology – the weight loss demands investigation 1
• Do not delay endoscopy to trial iron supplementation first – this is an urgent indication for fast-track referral given malignancy risk 1
• Do not perform only colonoscopy – upper endoscopy reveals bleeding sources in 30-50% of cases and identifies celiac disease and atrophic gastritis 2, 4
• Do not assume normal ferritin excludes iron deficiency in the setting of inflammation or chronic disease; check transferrin saturation 1, 2

Iron Replacement Strategy

While pursuing diagnostic workup, initiate iron replacement:

• Start oral iron supplementation with 100-200 mg elemental iron daily 3
• Consider intravenous iron if malabsorption is identified (celiac disease, atrophic gastritis) or if oral iron is not tolerated 1, 3
• A hemoglobin rise ≥10 g/L within 2 weeks confirms absolute iron deficiency even if iron studies were equivocal 1