What is the recommended treatment for a 33-year-old woman with hypoferritinemia (low ferritin level) and normal Complete Blood Count (CBC)?

Treatment of Hypoferritinemia with Normal CBC in a 33-Year-Old Woman

This patient requires oral iron supplementation with ferrous sulfate 200 mg three times daily (providing approximately 65 mg elemental iron per dose) for at least 3 months to replenish depleted iron stores, even though she is not anemic. 1, 2

Diagnostic Interpretation

• A ferritin of 28 μg/L in a premenopausal woman indicates depleted iron stores requiring treatment, as ferritin ≤30 μg/L is the appropriate threshold for this population 2, 3
• The normal CBC indicates this is iron deficiency without anemia (also called latent iron deficiency or iron depletion) 3
• Iron deficiency at all levels—including non-anemic iron deficiency—should be treated because iron is essential for optimal cognitive function and physical performance beyond its role in hemoglobin production 3

Investigation for Underlying Cause

Before or concurrent with treatment, evaluate for the source of iron loss:

• Obtain a detailed menstrual history to assess for menorrhagia, though history alone is unreliable for quantifying blood loss 1, 2
• Consider gastrointestinal evaluation (upper endoscopy with small bowel biopsy and colonoscopy) as significant GI pathology can occur even in menstruating women 2
• Screen for celiac disease with serologic testing, as this commonly causes iron malabsorption 2
• Test for H. pylori infection, which can impair iron absorption 2
• Assess dietary intake and use of NSAIDs, which can cause occult GI blood loss 1

Important caveat: The combination of low ferritin and reproductive age mandates investigation for pathologic causes beyond menstruation, as premenopausal status does not exclude serious underlying conditions 2

Iron Replacement Protocol

Dosing Strategy

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily is the standard, most cost-effective regimen 1, 2
• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated 1
• Liquid preparations may be better tolerated when tablets cause side effects 1

Optimization of Absorption

• Take on an empty stomach when possible for optimal absorption 2
• Co-administer with 500 mg vitamin C (ascorbic acid) to enhance iron absorption 1, 2
• Avoid tea, coffee, and calcium supplements around dosing times as they inhibit absorption 2

Alternative approach: Recent evidence suggests alternate-day dosing (rather than daily) may provide better absorption with fewer adverse effects, though this is not yet standard practice 1

Duration of Treatment

• Continue iron supplementation for 3 months after correction of ferritin levels to adequately replenish body stores 1
• Treatment duration will typically be 3-6 months total in non-anemic iron deficiency 3

Monitoring Response

• Recheck ferritin and CBC at 8-10 weeks after starting therapy 1, 3
• Target ferritin goal is ≥50 ng/mL in the absence of inflammation 2
• Do not check ferritin earlier than 8 weeks, as levels may be falsely elevated immediately after starting supplementation 1
• After achieving target ferritin, monitor every 3 months for the first year, then annually 1

Managing Side Effects

• Gastrointestinal side effects (constipation, diarrhea, nausea) are common with oral iron 1
• If side effects occur, consider reducing to once or twice daily dosing, or switching formulations 1
• Using preparations with reasonable elemental iron content (28-50 mg per dose rather than higher amounts) may reduce side effects while maintaining efficacy 3

When to Consider IV Iron

Intravenous iron is not indicated for this patient initially but should be considered if: 1, 3

• Repeated failure of oral therapy despite adequate trial
• Severe gastrointestinal intolerance preventing oral use
• Concomitant disease requiring urgent iron repletion

Critical Safety Considerations

• Do not supplement iron if ferritin is normal or elevated, as this is potentially harmful and associated with increased lipid peroxidation 1, 3, 4
• Ensure no contraindications exist (hemochromatosis, thalassemia, chronic transfusions) before starting supplementation
• If C-reactive protein is elevated, ferritin may be falsely normal despite true iron deficiency, as ferritin is an acute phase reactant 1, 3

Long-Term Management

• If ferritin repeatedly drops after discontinuing supplementation, consider intermittent oral iron (1-2 times weekly) for maintenance 3
• Provide dietary counseling to integrate heme iron sources and avoid inhibitors of absorption 1
• Monitor ferritin every 6-12 months in patients with recurrent depletion 3