In an adult with low serum iron, low ferritin, and normal TIBC (total iron‑binding capacity), what is the most likely diagnosis and recommended management?

Low Iron, Low Ferritin, Normal TIBC: Diagnosis and Management

This laboratory pattern is atypical and suggests either early-stage absolute iron deficiency before compensatory TIBC elevation occurs, or a mixed picture where inflammation is suppressing the expected TIBC rise—you must check inflammatory markers (CRP, ESR) immediately to distinguish these scenarios. 1

Understanding the Atypical Laboratory Pattern

The classic presentation of absolute iron deficiency shows:

• Low serum iron
• Elevated TIBC (>70 μmol/L or >400 μg/dL) 2, 3
• Low ferritin (<15-30 μg/L) 1, 4
• Low transferrin saturation (<16-20%) 1

Your patient's normal TIBC is unexpected and requires explanation. 2, 3

Two Most Likely Scenarios:

Scenario 1: Very Early Iron Deficiency

• Iron stores are depleted (low ferritin) but the body has not yet mounted a compensatory increase in TIBC 2
• This represents Stage 1 iron deficiency where stores are exhausted but erythropoiesis is not yet significantly impaired 5

Scenario 2: Coexistent Inflammation Masking Iron Deficiency

• Inflammation, chronic infection, or malignancy suppresses TIBC elevation despite true iron deficiency 1
• Conditions like inflammatory bowel disease, chronic kidney disease, or occult malignancy can cause this pattern 1, 5
• This is the more concerning possibility that must be ruled out. 1

Immediate Diagnostic Algorithm

Step 1: Check Inflammatory Markers

• Measure CRP and ESR immediately 1
• If CRP/ESR are elevated: suspect anemia of chronic disease coexisting with iron deficiency 1
• If CRP/ESR are normal: likely early absolute iron deficiency 1

Step 2: Calculate Transferrin Saturation

• Formula: (Serum Iron × 100) ÷ TIBC 1
• TSAT <16% confirms iron deficiency regardless of ferritin level 1
• TSAT <20% in the presence of inflammation indicates functional iron deficiency 1, 4

Step 3: Assess Ferritin in Context

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency 1, 4
• Ferritin 15-30 μg/L indicates depleted iron stores 1, 4
• If ferritin is 30-100 μg/L with elevated CRP/ESR, this represents mixed iron deficiency (absolute + functional) 1, 4

Step 4: Identify the Source of Iron Loss

For all adult men and non-menstruating women:

• Gastrointestinal evaluation is mandatory—9% of patients >65 years with iron deficiency have GI malignancy 6
• Begin with colonoscopy if age >50 years 6
• Screen for celiac disease with tissue transglutaminase antibodies (present in 3-5% of iron deficiency cases) 1, 5
• Test for H. pylori non-invasively 1

For premenopausal women:

• Assess menstrual blood loss history (duration ≥4 days increases risk) 7
• Screen for celiac disease and H. pylori 1, 5
• Reserve bidirectional endoscopy for: age ≥50 years, GI symptoms, positive celiac/H. pylori testing, or failure to respond to iron therapy after 8-10 weeks 1, 5

Treatment Protocol

Initiate Iron Supplementation Immediately

• Do not wait for investigation results to start treatment 1, 5
• Ferrous sulfate 325 mg daily (65 mg elemental iron) or alternate-day dosing 5
• Alternate-day dosing may improve absorption and reduce GI side effects 5
• Take on empty stomach for optimal absorption, or with meals if GI symptoms occur 5

Expected Response

• Hemoglobin should rise ≥10 g/L within 2 weeks 1
• If no response, consider malabsorption, non-compliance, ongoing blood loss, or need for IV iron 1, 5

When to Use Intravenous Iron

• Oral iron intolerance or malabsorption (celiac disease, post-bariatric surgery) 5
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer) 5
• Ongoing blood loss 5
• Second and third trimesters of pregnancy 5

Follow-Up and Monitoring

• Repeat CBC and ferritin at 8-10 weeks 1, 5
• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 1
• For high-risk patients (menstruating females, vegetarians, athletes), screen ferritin every 6-12 months 1
• Do not continue daily iron supplementation once ferritin normalizes—this is potentially harmful 5

Critical Pitfalls to Avoid

Pitfall 1: Assuming Normal TIBC Excludes Iron Deficiency

• Normal TIBC does not exclude iron deficiency—it may indicate early deficiency or coexistent inflammation 2, 3
• Always interpret TIBC alongside ferritin, serum iron, and inflammatory markers 1

Pitfall 2: Missing Occult Malignancy

• Normal TIBC with low iron and low ferritin can indicate chronic disease masking iron deficiency 1, 3
• Check CRP/ESR to identify inflammation that may signal underlying malignancy or chronic disease 1

Pitfall 3: Inadequate GI Investigation

• In adult men and non-menstruating women, failure to investigate the GI tract is a serious error 6
• 9% of elderly patients with iron deficiency have GI cancer 6

Pitfall 4: Overlooking Celiac Disease

• Celiac disease is present in 3-5% of iron deficiency cases and causes treatment failure if undiagnosed 1, 5
• Always screen with tissue transglutaminase antibodies 1, 5