Managing Low Ferritin in Adult Men
In adult men with low ferritin, immediately initiate oral iron supplementation (ferrous sulfate 325 mg daily or 60 mg elemental iron on alternate days) while simultaneously investigating for the underlying cause, as approximately one-third of men with iron deficiency have underlying gastrointestinal pathology, including malignancy. 1, 2
Diagnostic Thresholds and Interpretation
Defining Low Ferritin
- Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and definitively confirms the diagnosis 1
- Ferritin 15-30 μg/L indicates depleted iron stores and generally warrants treatment 1
- Ferritin <45 μg/L provides optimal sensitivity-specificity balance (specificity 0.92) for clinical decision-making 1
- Normal reference range for adult men is 20-250 μg/L, though this represents population averages rather than individual thresholds 1, 3
Critical Caveat: Rule Out Inflammation
- Ferritin is an acute-phase protein that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency 1, 4
- In inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer), the diagnostic threshold shifts upward to ferritin <100 μg/L 4
- Check C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) if ferritin is 30-100 μg/L to determine if inflammation is falsely elevating ferritin 4
- Calculate transferrin saturation (TSAT): values <20% indicate iron deficiency even with higher ferritin levels 1, 4
Mandatory Investigation for Underlying Cause
Gastrointestinal Evaluation
Men with newly diagnosed iron deficiency require urgent bidirectional endoscopy (gastroscopy and colonoscopy) as the first-line investigation, as approximately 30% have significant upper GI pathology and gastrointestinal malignancies commonly present this way 1, 5
- Upper GI findings (malignancy, peptic ulcers, Helicobacter pylori gastritis, arteriovenous malformations) occur in 30% of cases 5
- Lower GI findings (adenomas, arteriovenous malformations, malignancy) occur in 6.7% of cases 5
- CT colonography is a reasonable alternative if colonoscopy is not suitable 1
Additional Screening Tests
- Screen for celiac disease with tissue transglutaminase antibodies (tTG-IgA), as it is found in 3-5% of iron deficiency cases 1
- Perform urinalysis or urine microscopy to exclude urinary blood loss 1
- Test for H. pylori non-invasively (stool antigen or urea breath test) 1
- Consider complete blood count to assess for anemia and mean cell volume 1, 2
Iron Supplementation Protocol
First-Line Oral Iron Therapy
- Start ferrous sulfate 325 mg daily (65 mg elemental iron) or 60 mg elemental iron on alternate days 6, 2
- Alternate-day dosing may improve absorption and reduce gastrointestinal side effects compared to daily dosing 2
- Take on empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur 2
- Expected side effects include constipation, nausea, or diarrhea 2
When to Use Intravenous Iron
Intravenous iron is indicated for: 2
- Oral iron intolerance or poor absorption (celiac disease, post-bariatric surgery)
- Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)
- Ongoing blood loss that cannot be controlled
- Failure to respond to adequate oral iron therapy after 8-10 weeks
Follow-Up and Monitoring
Response Assessment
- Repeat complete blood count and ferritin in 8-10 weeks to assess response 2
- A hemoglobin rise ≥10 g/L within 2 weeks is highly suggestive of absolute iron deficiency, even if initial iron studies were equivocal 1
- Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 2
If No Improvement After 8-10 Weeks
Consider: 2
- Malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
- Non-compliance with therapy
- Ongoing occult blood loss requiring further investigation
- Need for intravenous iron supplementation
- Urgent gastrointestinal evaluation if not already performed 1
Long-Term Surveillance
- For men with recurrent low ferritin, screen every 6-12 months depending on risk factors 2
- Do not continue daily iron supplementation once ferritin normalizes, as this is potentially harmful 2
Common Pitfalls to Avoid
Never assume normal ferritin excludes iron deficiency in inflammatory conditions—always check transferrin saturation, as ferritin can be falsely elevated 4
Do not delay gastrointestinal investigation in men, even if symptoms are absent—malignancy can present with iron deficiency alone 1, 5
Do not overlook celiac disease—it is present in 3-5% of iron deficiency cases and easily missed without serologic screening 1
Recognize that ferritin 40-100 μg/L in men still warrants GI endoscopy, as 30% have significant upper GI pathology even in this "low-normal" range 5
In chronic kidney disease patients, use different thresholds: absolute iron deficiency is defined as ferritin <100 ng/mL combined with TSAT <20% 4