What is the most likely cause of iron deficiency anemia in a 20-year-old male with no significant medical history?

Iron Deficiency Anemia in a 20-Year-Old Male

In a 20-year-old male with iron deficiency anemia, gastrointestinal blood loss is the most likely cause and requires comprehensive investigation with bidirectional endoscopy (gastroscopy and colonoscopy), regardless of the absence of GI symptoms. 1, 2

Primary Mechanism in Young Men

• Occult gastrointestinal bleeding is the leading cause of iron deficiency anemia in males of any age, as iron loss through blood loss exceeds the body's conservation capacity 3, 4
• The most common GI sources in this age group include:
  • NSAID-induced mucosal damage (frequently unreported over-the-counter use) 1, 5
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 1
  • Celiac disease (found in 3-5% of all iron deficiency anemia cases) 2, 5
  • Peptic ulcer disease 1
  • Meckel's diverticulum 1

Critical Malabsorption Causes

• Celiac disease must be screened in every patient with unexplained iron deficiency anemia, as it accounts for 2-5% of cases and is easily missed 1, 5
• Small bowel biopsies should be obtained during upper endoscopy even without positive serology if clinical suspicion exists 1, 5
• Other malabsorption causes include bacterial overgrowth, Whipple's disease, and intestinal lymphangiectasia 1

Less Common but Important Causes

• Urinary tract bleeding should be excluded with urinalysis in all cases 5
• Frequent blood donation can cause iron deficiency 5
• Poor dietary iron intake, particularly in lower socioeconomic populations 5
• Hookworm infection in endemic areas 1

Diagnostic Approach Algorithm

Step 1: Confirm iron deficiency

• Serum ferritin <12 μg/dL is diagnostic; ferritin >100 μg/dL essentially excludes iron deficiency 1
• Note that ferritin may be falsely elevated with concurrent inflammation, malignancy, or hepatic disease 1, 6

Step 2: Obtain targeted history

• Explicitly ask about all NSAID use (including over-the-counter medications like ibuprofen, as patients often don't report these) 5
• Document aspirin, anticoagulant, and antiplatelet use 1, 5
• Assess dietary iron intake, though borderline deficient diets should not preclude full GI investigation 1
• Screen for GI symptoms (though these rarely correlate with findings) 1

Step 3: Mandatory investigations

• Upper GI endoscopy with small bowel biopsies (reveals cause in 30-50% of patients) 1
• Colonoscopy or barium enema (dual pathology occurs in 10-15% of patients) 1, 6
• Celiac serology (tissue transglutaminase antibody) 5, 7
• Urinalysis to exclude urinary tract bleeding 5

Step 4: Consider additional testing if initial workup negative

• Wireless capsule endoscopy for small bowel evaluation in refractory cases 2

Common Pitfalls to Avoid

• Do not stop investigating after finding one cause, as multiple etiologies coexist in 10-15% of patients 1, 6
• Do not accept minor findings (oesophagitis, erosions, aphthous ulceration, single peptic ulcer) as the sole cause without completing lower GI investigation 1
• Do not assume dietary deficiency is the cause even with a positive dietary history; full GI investigation is still required 1
• Do not miss celiac disease by failing to obtain small bowel biopsies during upper endoscopy 1, 5
• Do not overlook unreported NSAID use; patients frequently don't mention over-the-counter medications 5

Treatment Considerations

• Iron replacement with ferrous sulfate 200 mg three times daily (65 mg elemental iron per dose) should be initiated 6
• Continue iron for 3 months after hemoglobin normalizes to replenish stores 6
• Failure to respond to oral iron indicates poor compliance, misdiagnosis, continued blood loss, or malabsorption 6
• Approximately one-third of men with iron deficiency anemia have underlying GI pathology, making investigation essential 2, 6