Should a gastrointestinal workup be performed in a young (<40 years) patient with iron‑deficiency anemia of unknown cause?

GI Workup in Young Patients with Iron Deficiency Anemia

Yes, young patients with unexplained iron deficiency anemia require gastrointestinal evaluation, though the approach differs based on sex and specific risk factors.

Risk Stratification by Age and Sex

Premenopausal Women (<40 years)

• The AGA suggests bidirectional endoscopy over iron replacement alone (conditional recommendation, moderate evidence), though this is less urgent than in older patients 1
• Young women without alarm features may reasonably defer endoscopy if menorrhagia or dietary deficiency adequately explains the anemia, particularly if they place high value on avoiding procedural risks 1
• However, 2-3% of IDA patients have celiac disease, making serologic screening (anti-tissue transglutaminase or anti-endomysial antibodies) essential even in young women 1, 2

Young Men (<40 years)

• Young men require more aggressive evaluation because menstrual loss cannot explain their anemia 3
• In a cohort of 2,061 young men (18-30 years) with iron deficiency, significant GI pathology was found in only 1.7% overall, but included inflammatory bowel disease (1.2%), celiac disease (0.4%), and peptic disease (0.1%) 4
• No GI malignancies were detected in this young male cohort during 3,150 person-years of follow-up 4

Initial Non-Invasive Workup

Before proceeding to endoscopy, obtain:

• Celiac serology (anti-tissue transglutaminase antibodies) – positive in 2-6% of IDA patients across all ages 2, 5
• H. pylori testing (urea breath test or stool antigen) – H. pylori gastritis was significantly more prevalent (57%) in patients whose bleeding source remained unidentified 6
• Inflammatory markers (C-reactive protein or fecal calprotectin) to screen for inflammatory bowel disease 4
• Urinalysis to exclude renal pathology as a chronic blood loss source 2, 5

When to Proceed with Endoscopy in Young Patients

High-Risk Features Mandating Bidirectional Endoscopy:

• Male sex (positive predictive value for GI lesions, p=0.004) 3
• Weight loss >20% of body weight in 6 months (p=0.012) 3
• Chronic diarrhea or change in bowel habits (p=0.006 and p=0.043 respectively) 3
• Hemoglobin <10 g/dL (p=0.054) 3
• Elevated CEA (p=0.039) 3
• Failure to respond to iron therapy after 3 months 1
• Transfusion-dependent anemia 1

Lower-Risk Young Women:

• In one study, **23% of women <51 years had zero risk factors** (male sex, age >50, weight loss, diarrhea, bowel habit change, epigastric tenderness, elevated CEA, Hb <10 g/dL), and none had significant GI lesions (negative predictive value 100%) 3
• These patients may reasonably trial iron supplementation with close monitoring rather than immediate endoscopy 1, 4

The Bidirectional Endoscopy Approach

When endoscopy is indicated:

• Perform both upper endoscopy and colonoscopy, as dual pathology occurs in 10-15% of patients 1, 2
• Obtain duodenal biopsies during upper endoscopy regardless of celiac serology results, as serologic sensitivity is imperfect 2, 5
• Do not accept esophagitis, erosions, or peptic ulcer as the sole explanation until colonoscopy excludes lower GI pathology 1, 2
• Upper endoscopy identifies a bleeding source in 30-50% of cases 1

Critical Pitfalls to Avoid

• Do not attribute IDA solely to menstruation without excluding GI pathology in premenopausal women with risk factors 3
• Do not skip colonoscopy even if upper endoscopy reveals a lesion, as 10-15% have concurrent upper and lower tract pathology 1, 2
• Do not accept dietary deficiency alone as the explanation without completing GI evaluation in patients with persistent anemia 1
• Do not delay celiac testing – it is present in 2-6% of IDA patients and is easily missed without systematic screening 2, 5

Follow-Up Strategy

• Iron supplementation should continue for 3 months after hemoglobin normalization to replenish stores 1
• Monitor hemoglobin and MCV at 3-month intervals for 1 year, then annually 1
• In young men with iron deficiency but no anemia, 9.8% developed overt anemia during follow-up, and anemia development increased GI pathology risk 3.6-fold (95% CI 1.34-8.32) 4
• Further investigation is warranted only if anemia recurs despite adequate iron replacement 1

Prognosis in Young Patients

• Among patients with negative initial endoscopy, 69% had resolved anemia at 48-month follow-up without identifying a bleeding source 6
• The prognosis of IDA with negative endoscopy is generally favorable in young patients 6
• No GI malignancies were detected in the young male cohort (18-30 years) during extended follow-up 4