How do I manage a patient with normal serum iron, low ferritin, and normal hemoglobin?

Management of Low Ferritin (14 ng/mL) with Normal Serum Iron (115 μg/dL)

This patient has absolute iron deficiency confirmed by ferritin <15 ng/mL and requires immediate oral iron supplementation plus investigation for the underlying cause of iron loss. 1

Understanding the Laboratory Pattern

Your patient presents with a classic early-stage absolute iron deficiency where:

• Ferritin 14 ng/mL is below the diagnostic threshold of <15 ng/mL, which has 99% specificity for absolute iron deficiency 2, 1
• The normal serum iron (115 μg/dL) does not exclude iron deficiency because serum iron shows diurnal variation and reflects only circulating iron in transit, not total body stores 2
• Ferritin is the earliest and most specific marker of depleted iron stores, becoming abnormal before other iron parameters 2
• This pattern represents Stage 1 iron deficiency: depleted iron stores with normal hemoglobin (not yet anemic) 2

Critical point: Even without anemia, this patient likely experiences symptoms including fatigue, reduced exercise tolerance, difficulty concentrating, and possibly restless legs syndrome 3

Immediate Treatment Protocol

Start oral iron supplementation immediately—do not wait for completion of diagnostic workup: 1, 3

• Ferrous sulfate 325 mg daily (65 mg elemental iron) OR 60-65 mg elemental iron every other day 1, 3
• Alternate-day dosing improves absorption by 30-50% and reduces gastrointestinal side effects (constipation, nausea, diarrhea) 4
• Take on empty stomach for optimal absorption; if gastrointestinal symptoms occur, take with meals 4
• Expected response: hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the sole cause 1

Mandatory Investigation for Iron Loss

The diagnostic algorithm depends on patient demographics:

For Adult Men or Postmenopausal Women:

Urgent bidirectional endoscopy (upper GI gastroscopy + colonoscopy) is mandatory because iron deficiency may be the sole manifestation of gastrointestinal malignancy 1

For Premenopausal Women:

1. Screen for celiac disease with tissue transglutaminase IgA antibodies—celiac disease accounts for 3-5% of iron deficiency cases and causes treatment failure if missed 1, 3
2. Test for Helicobacter pylori (stool antigen or urea breath test) because it impairs iron absorption 1
3. Assess menstrual blood loss history—the most common cause in this population 1

Reserve bidirectional endoscopy for premenopausal women only if: 1

• Age ≥50 years (higher malignancy risk)
• Gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood)
• Positive celiac or H. pylori testing requiring confirmation
• Lack of response to adequate oral iron after 8-10 weeks
• Strong family history of colorectal cancer

Calculate Transferrin Saturation

You must calculate TSAT to complete the iron assessment: 2, 1

TSAT = (Serum iron × 100) ÷ Total iron-binding capacity (TIBC)

• TSAT <16-20% confirms iron deficiency and indicates insufficient iron for red blood cell production 2, 1
• If TIBC is not available, order it along with a complete blood count to assess for microcytic anemia (low MCV, low MCH) 1

Follow-Up and Monitoring

• Repeat CBC and ferritin at 8-10 weeks to assess therapeutic response 1, 3
• Target ferritin >100 ng/mL to fully restore iron stores and prevent recurrence 4, 1
• Continue oral iron for 3 months after hemoglobin normalizes to achieve target ferritin 1
• If no improvement after 8-10 weeks, consider malabsorption, non-compliance, ongoing blood loss, or need for IV iron 1

Indications for Intravenous Iron

Switch to intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) if any of the following apply: 1, 3

• Oral iron intolerance (severe nausea, constipation, diarrhea)
• Confirmed malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss exceeding oral replacement capacity
• Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer)
• Pregnancy in second/third trimester
• Lack of hemoglobin response after 8-10 weeks of adequate oral iron

IV iron produces reticulocytosis within 3-5 days and yields mean hemoglobin increase of ≈8 g/L over 8 days 1

Long-Term Prevention

For patients at risk of recurrent iron deficiency: 1

• Menstruating females: screen ferritin every 6 months 1
• Males, vegetarians, athletes: screen ferritin annually 1
• Do not continue daily iron supplementation once ferritin normalizes—this is potentially harmful 1

Critical Pitfalls to Avoid

• Do not assume normal serum iron excludes iron deficiency—ferritin is the definitive test for iron stores 2, 1
• Do not overlook celiac disease screening (3-5% prevalence in iron deficiency)—missing this diagnosis leads to treatment failure 1, 3
• Do not delay endoscopic evaluation in high-risk patients (men, postmenopausal women, age ≥50, alarm symptoms)—GI malignancy can present solely with iron deficiency 1
• Do not discontinue iron therapy once hemoglobin normalizes—continue for 3 additional months to restore ferritin >100 ng/mL 1