What is the best course of treatment for an adult patient with low ferritin (iron) levels and no significant medical history?

Management of Low Ferritin in Adults Without Significant Medical History

Start oral iron supplementation immediately with ferrous sulfate 325 mg daily (or every other day for better absorption and tolerability) and continue for 3 months after hemoglobin normalizes to replenish iron stores. 1, 2

Diagnostic Confirmation and Workup

Serum ferritin <30 μg/L confirms iron deficiency in healthy adults without inflammation and warrants treatment. 3, 4 The British Society of Gastroenterology establishes that ferritin <15 μg/L is highly specific (99% specificity) for absent iron stores, while levels <30 μg/L indicate low body iron stores. 3

Essential Initial Testing

• Check transferrin saturation if ferritin is 15-45 μg/L to distinguish early absolute iron deficiency (transferrin saturation <20%) from other causes 1
• Measure inflammatory markers (CRP/ESR) because ferritin is an acute-phase protein that can appear falsely normal during inflammation 3, 1, 4
• Screen for celiac disease with tissue transglutaminase (TTG) antibodies, as 2-3% of iron deficiency cases are due to celiac disease 3
• Perform urinalysis to exclude urinary tract blood loss 3

Investigation for Underlying Cause

The threshold for gastrointestinal investigation depends critically on patient demographics:

Men and Postmenopausal Women

• Bidirectional endoscopy (gastroscopy and colonoscopy) is mandatory even without anemia, as the risk of GI malignancy is significant 3, 5
• Investigation should occur at any level of ferritin <45 μg/L, particularly if accompanied by anemia 3
• Small bowel biopsies should be obtained during gastroscopy to detect celiac disease 3

Premenopausal Women

• GI investigation is generally not warranted if there is a clear history of menorrhagia or recent pregnancy without other concerning features 3
• However, maintain a low threshold for investigation if GI symptoms are present, family history of GI pathology exists, or iron deficiency persists despite treatment 3

Key Investigation Pitfalls to Avoid

• Do not perform fecal occult blood testing—it is insensitive and non-specific 3, 1
• Do not accept upper GI findings alone (esophagitis, gastritis, peptic ulcer) as the definitive cause without also examining the lower GI tract, as dual pathology occurs in 10-15% of cases 3
• Hemoglobin electrophoresis is recommended in patients with microcytosis and normal iron studies, particularly in appropriate ethnic backgrounds, to exclude thalassemia 3

Treatment Protocol

Oral Iron Therapy (First-Line)

• Ferrous sulfate 325 mg (65 mg elemental iron) daily is the standard dose 2, 6
• Every-other-day dosing improves absorption and reduces gastrointestinal side effects, which affect approximately 50% of patients 5, 6
• Co-administer with vitamin C to enhance absorption; avoid tea/coffee around dosing 1
• Continue for 3 months after hemoglobin normalizes to replenish iron stores 3, 1

Monitoring Response

• Recheck hemoglobin at 2-4 weeks—expect a rise of 1-2 g/dL 1, 5
• If no response occurs, consider malabsorption, ongoing bleeding, non-compliance, or misdiagnosis 1
• After normalization, monitor every 3 months for 1 year, then annually 3, 1

When to Use Intravenous Iron

Intravenous iron is indicated for: 5, 6

• Oral iron intolerance or poor absorption (celiac disease, post-bariatric surgery)
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Ongoing blood loss requiring urgent correction
• Second and third trimesters of pregnancy
• Failure to respond to adequate oral iron trial

Critical Clinical Pearls

Never dismiss iron deficiency based solely on ferritin 30-100 μg/L—always check transferrin saturation and inflammatory markers, as ferritin can be falsely elevated by inflammation. 1 In inflammatory conditions, ferritin up to 100 μg/L can still represent iron deficiency if transferrin saturation is <20%. 1

Ferritin >150 μg/L makes absolute iron deficiency unlikely even in the presence of inflammation, though functional iron deficiency may still exist in chronic disease states. 3, 1

Iron deficiency commonly causes non-hematologic symptoms including fatigue, restless legs syndrome (32-40% of cases), pica (40-50%), difficulty concentrating, irritability, and depression—these symptoms may occur even without anemia. 6 In fact, pruritus (generalized itching) can be an unusual presenting symptom that responds rapidly to iron replacement. 3