What is the recommended treatment for an adult patient with no significant medical history and low iron blood tests (hypoferritinemia)?

Treatment of Low Iron Blood Tests (Hypoferritinemia) in Adults

For an adult with no significant medical history and confirmed low iron stores (hypoferritinemia), start with oral iron therapy using ferrous sulfate 325 mg daily (or one tablet every other day if not tolerated), and monitor hemoglobin response within 2-4 weeks to confirm iron deficiency and guide further management. 1

Confirming Iron Deficiency

Before initiating treatment, confirm true iron deficiency with appropriate testing:

• Serum ferritin is the single most useful marker for diagnosing iron deficiency, with a threshold of <30 μg/L indicating deficiency in healthy adults over 15 years 1, 2
• Measure transferrin saturation (<20% suggests iron deficiency) if ferritin results are equivocal or if inflammation is suspected 1
• Exclude inflammatory conditions by checking C-reactive protein, as inflammation can falsely elevate ferritin levels despite true iron deficiency 3
• A hemoglobin rise ≥10 g/L within 2 weeks of starting iron therapy strongly confirms absolute iron deficiency, even if initial iron studies were equivocal 1

First-Line Treatment: Oral Iron

The initial treatment should be one tablet daily of ferrous sulfate (325 mg, containing 65 mg elemental iron), ferrous fumarate, or ferrous gluconate 1, 4:

• If gastrointestinal side effects occur (nausea, constipation, diarrhea), reduce to one tablet every other day rather than switching to different iron salts, as evidence does not support superiority of alternative formulations 1
• Preparations containing 28-50 mg elemental iron may improve compliance by reducing side effects 3
• Continue oral iron for 2-3 months after hemoglobin normalizes to replenish iron stores 1

Monitoring Response

Check hemoglobin every 4 weeks until normalized 1:

• If hemoglobin does not increase by ≥10 g/L after 2 weeks of daily oral iron, this predicts treatment failure with 90% sensitivity and 79% specificity 5
• After hemoglobin normalization, monitor every 3 months for 12 months, then every 6 months for 2-3 years to detect recurrent deficiency 1

When to Consider Intravenous Iron

Switch to intravenous iron if 1, 5, 2:

• Oral iron intolerance persists despite alternate-day dosing
• Failure to respond to adequate oral iron trial (no hemoglobin rise after 2 weeks)
• Malabsorption conditions are present (celiac disease, post-bariatric surgery, inflammatory bowel disease)
• Ongoing blood loss that cannot be controlled

Preferred IV formulations include ferric carboxymaltose or ferric derisomaltose, which allow single or two-dose regimens rather than multiple infusions 5

Investigating the Underlying Cause

Even in asymptomatic patients, identify the source of iron deficiency 1, 2:

• Dietary assessment: inadequate iron intake, vegetarian/vegan diet
• Menstrual history: heavy or prolonged bleeding in premenopausal women
• Gastrointestinal evaluation: Consider screening for celiac disease (affects 3-5% of iron deficiency cases) with serologic testing 1
• Medication review: NSAIDs, antiplatelet agents, anticoagulants that may cause occult bleeding 1

Important caveat: Men and postmenopausal women with confirmed iron deficiency warrant gastroscopy and colonoscopy to exclude gastrointestinal malignancy, as approximately one-third have underlying bleeding abnormalities and one-third of those prove to be cancer 1. However, this does not apply to your patient with no significant medical history if they are premenopausal or have an obvious non-GI cause.

Special Considerations for Non-Anemic Iron Deficiency

If your patient has low ferritin but normal hemoglobin (non-anemic iron deficiency):

• Treatment is reasonable if symptomatic (fatigue, restless legs syndrome, difficulty concentrating, exercise intolerance) 1, 3, 2
• Use the same oral iron regimen as for iron deficiency anemia 3
• Recheck ferritin after 8-10 weeks of treatment 3
• Do not supplement if ferritin is normal or high, as this is inefficient, causes side effects, and may be harmful 3

Common Pitfalls to Avoid

• Don't defer iron replacement while awaiting investigations unless colonoscopy is imminent 1
• Don't switch between different oral iron salts for intolerance—try alternate-day dosing or move to IV iron instead 1
• Don't continue long-term daily iron supplementation once stores are replenished, as this is potentially harmful 3
• Don't ignore treatment failure—if no response after 2 weeks, investigate for malabsorption, ongoing blood loss, or consider IV iron 5, 2