What are the likely causes of mild iron deficiency in an adult male?

Causes of Mild Iron Deficiency in Adult Males

Primary Cause: Gastrointestinal Blood Loss

In adult males with mild iron deficiency, gastrointestinal blood loss is the predominant mechanism and requires urgent investigation to exclude malignancy, even in the complete absence of GI symptoms. 1, 2

• Approximately one-third of men presenting with iron deficiency have an underlying pathological GI abnormality, and roughly one-third of these prove to be malignancies. 3
• The most common bleeding sources include colon cancer, gastric cancer, peptic ulcer disease, hiatal hernia with linear erosions, colonic vascular ectasia, and colonic polyps. 4
• Bidirectional endoscopy (gastroscopy and colonoscopy) should be performed as first-line investigation in all adult males with newly diagnosed iron deficiency, regardless of symptom absence. 1, 3

Critical Non-Bleeding Causes

Celiac Disease

• Celiac disease accounts for 3-5% of all iron deficiency cases and must be screened for in every male patient with unexplained iron deficiency. 1, 2, 3
• Screen with tissue transglutaminase antibody, and obtain duodenal biopsies during upper endoscopy even if serology is negative but clinical suspicion remains. 2, 3

NSAID-Induced Mucosal Damage

• Chronic NSAID use causes occult gastrointestinal blood loss even without overt bleeding symptoms or ulceration. 2
• Explicitly ask about all NSAID use, including over-the-counter ibuprofen, naproxen, and aspirin, as patients frequently fail to report these medications. 2, 3
• Anticoagulants and antiplatelet agents can unmask underlying vascular lesions like angiodysplasia. 2

Malabsorption Disorders

• Atrophic gastritis is found in a substantial proportion of iron deficiency cases and impairs iron absorption without causing bleeding. 4
• Helicobacter pylori gastritis can contribute to iron deficiency through altered gastric acid production and direct iron sequestration. 4

Nutritional Deficiency

• Poor dietary iron intake occurs particularly in men of lower socioeconomic status with limited access to iron-rich foods. 2
• Vegetarian diets are inherently low in heme iron (the most bioavailable form), though this can be partially compensated by consuming iron with vitamin C. 1

Less Common But Important Causes

Urinary Tract Blood Loss

• Urinalysis or urine microscopy should be performed in all cases to exclude urinary tract bleeding. 1, 2

Frequent Blood Donation

• Regular blood donation depletes iron stores over time and represents a common overlooked cause. 2

Chronic Disease States

• Chronic kidney disease impairs erythropoietin production and iron utilization. 2
• Chronic inflammatory conditions can cause functional iron deficiency where ferritin appears normal despite depleted stores. 1
• Androgen deprivation therapy in prostate cancer survivors suppresses erythropoiesis. 2

Diagnostic Algorithm

Initial Laboratory Confirmation

• Serum ferritin <15 μg/L is highly specific for iron deficiency (specificity 0.99). 1
• Ferritin <45 μg/L warrants consideration of GI investigation, especially with chronic inflammation. 1
• A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy strongly suggests absolute iron deficiency even with equivocal iron studies. 1, 3

Mandatory Initial Workup

1. Celiac disease screening with tissue transglutaminase antibody 2, 3
2. Urinalysis or urine microscopy 1, 2
3. Comprehensive medication history focusing on NSAIDs and anticoagulants 2, 3
4. Upper endoscopy with duodenal biopsies 1, 3
5. Colonoscopy (preferred over CT colonography) 1, 3

When Initial Endoscopy is Negative

• In young men (18-30 years) with mild iron deficiency and negative bidirectional endoscopy, significant GI pathology is uncommon (found in only 1.7% in one study). 5
• However, do not stop investigating after finding one minor cause, as multiple etiologies coexist in 10-15% of patients. 2, 3
• If both endoscopies are normal and anemia is not severe, trial of oral iron with NSAID cessation is reasonable, but close monitoring is essential. 6
• Consider small bowel evaluation with capsule endoscopy if iron deficiency persists or recurs despite treatment. 1, 6

Common Pitfalls to Avoid

• Assuming dietary deficiency is the sole cause even with a positive dietary history—full GI investigation is still required in adult males. 2
• Failing to screen for celiac disease results in missed diagnoses in 3-5% of cases. 2, 3
• Not asking specifically about over-the-counter NSAID use leads to missed diagnoses. 2
• Accepting minor endoscopic findings (such as small hiatal hernia) as the sole explanation without completing lower GI investigation. 3
• Stopping investigation after finding one cause without considering dual pathology. 2, 3

Iron Physiology Context

• In adult men, approximately 95% of iron required for red blood cell production is recycled from breakdown of old red blood cells, with only 5% from dietary sources. 1
• Men normally lose approximately 1 mg of iron daily through feces and desquamated cells. 1
• Men store approximately 1.0-1.4 g of body iron, significantly more than women (0.2-0.4 g), making iron deficiency in men particularly concerning for pathological blood loss. 1