What is the management for an adult patient with iron deficiency (ferritin 60 ng/mL), low transferrin saturation (15%), and normal hemoglobin levels?

Management of Iron Deficiency with Normal Hemoglobin

This patient has functional iron deficiency requiring iron supplementation, despite the normal hemoglobin and ferritin of 60 ng/mL, because the transferrin saturation of 15% confirms iron-deficient erythropoiesis. 1

Understanding the Diagnosis

Your patient presents with a paradoxical but increasingly recognized pattern:

• Ferritin 60 ng/mL appears "normal" by traditional laboratory reference ranges
• Transferrin saturation 15% is well below the 20% threshold, confirming inadequate iron delivery to the bone marrow 1, 2
• Normal hemoglobin indicates this is non-anemic iron deficiency (NAID)

The transferrin saturation of 15% is the critical diagnostic finding here. TSAT <16-20% indicates iron-deficient erythropoiesis regardless of ferritin levels, meaning the bone marrow lacks sufficient available iron for hemoglobin production. 1, 3

Why This Matters Despite Normal Hemoglobin

The British Society of Gastroenterology guidelines emphasize that ferritin levels <45 μg/L provide optimal sensitivity/specificity for iron deficiency, and your patient's ferritin of 60 ng/mL combined with TSAT 15% represents early-stage iron depletion before anemia develops. 4, 2

Non-anemic iron deficiency causes significant symptoms: fatigue, irritability, depression, difficulty concentrating, restless legs syndrome (32-40% of cases), pica (40-50%), exercise intolerance, and dyspnea. 3

Investigation Required

Mandatory Evaluation

In men and postmenopausal women, bidirectional endoscopy (upper and lower GI) is mandatory to exclude malignancy as a source of chronic blood loss. 4, 1, 5

Additional Testing

• Celiac disease screening (tissue transglutaminase antibody with IgA level) - found in 3-5% of iron deficiency cases 4
• Helicobacter pylori testing - common cause of iron deficiency 5
• Urinalysis to exclude urinary blood loss 4
• Inflammatory markers (CRP, ESR) to assess for chronic inflammatory conditions 1

Special Populations

For premenopausal women with heavy menstrual bleeding or recent pregnancy: GI investigation is generally not warranted in the absence of GI symptoms, family history of GI pathology, or other concerning features. Treatment of the bleeding source plus iron supplementation is appropriate. 4, 2, 5

Treatment Approach

First-Line: Oral Iron

Oral iron supplementation is first-line therapy for most patients without chronic inflammatory conditions. 5, 3

• Ferrous sulfate 325 mg daily (containing 65 mg elemental iron) 6, 3
• Alternative dosing: Every-other-day administration improves absorption and reduces side effects 5, 3
• Common pitfall: Approximately 50% of patients have decreased adherence due to GI adverse effects (nausea, constipation, abdominal discomfort) 5

When to Consider Intravenous Iron

IV iron should be considered if: 5, 3

• Oral iron intolerance or non-adherence
• Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Ongoing blood loss
• Pregnancy (second and third trimesters)

In chronic inflammatory states, IV iron bypasses hepcidin-mediated blockade of intestinal iron absorption, directly delivering iron to bone marrow. 1

Target Goals

• TSAT ≥20% to ensure adequate iron availability for erythropoiesis 4, 1
• Ferritin 100 ng/mL as a reasonable target 4

Monitoring Response

Evaluate response in 2-4 weeks after initiating oral iron therapy: 5

• Repeat CBC, ferritin, and transferrin saturation
• Reticulocytosis occurs at 3-5 days after IV iron administration, indicating bone marrow response 1
• If no response to oral iron: Switch to IV iron formulation 5, 3

Laboratory Timing After IV Iron

Do not check iron parameters within 4 weeks of IV iron infusion - circulating iron interferes with the assay. Optimal timing is 4-8 weeks after the last infusion. 1

Critical Clinical Pitfalls

• Don't dismiss low TSAT because ferritin appears "normal" - TSAT <20% indicates functional iron deficiency regardless of ferritin level 1
• Don't skip GI evaluation in men and postmenopausal women - recurrent blood loss accounts for 94% of iron deficiency cases, and malignancy must be excluded 5, 1
• Don't rely on hemoglobin alone - less than 50% of patients with anemia by hemoglobin criteria actually have iron deficiency in modern populations 1
• Don't forget celiac screening - it's found in 3-5% of iron deficiency cases and is easily treatable 4