With ferritin 11 ng/mL, serum iron 67 µg/dL, TIBC (total iron‑binding capacity) 397 µg/dL, transferrin saturation 17 %, UIBC (unsaturated iron‑binding capacity) 330 µg/dL, hemoglobin 13.4 g/dL, and MCV (mean corpuscular volume) 81 fL in an adult, what is the most likely diagnosis and how should it be evaluated and treated?

Iron Deficiency Without Anemia

Your laboratory values confirm absolute iron deficiency that requires treatment, even though your hemoglobin remains in the normal range. 1

Diagnosis

Your iron panel demonstrates classic absolute iron deficiency:

• Ferritin 11 ng/mL is well below the 30 ng/mL threshold, confirming depleted iron stores in the absence of inflammation 1
• Transferrin saturation 17% falls below the diagnostic cutoff of 20%, indicating iron-deficient erythropoiesis 2, 1
• Elevated TIBC 397 µg/dL reflects your body's compensatory attempt to capture more circulating iron when stores are empty 2, 1
• Elevated UIBC 330 µg/dL provides additional confirmation of vacant iron-binding sites on transferrin 1
• MCV 81 fL is at the lower end of normal, suggesting early microcytic changes that precede frank anemia 2
• Hemoglobin 13.4 g/dL remains adequate but will eventually decline if iron deficiency persists untreated 2

The combination of ferritin <15 µg/L and transferrin saturation <16% provides 100% specificity for depleted iron stores. 1

Mandatory Evaluation for Underlying Cause

Iron deficiency rarely occurs without an identifiable source of loss or inadequate intake, making investigation of the underlying cause essential. 1

Initial Laboratory Work-up

• C-reactive protein to exclude inflammation that might mask even lower ferritin values 1
• Complete metabolic panel with serum creatinine to calculate estimated glomerular filtration rate and assess for chronic kidney disease 1
• Celiac disease serologic screening (tissue transglutaminase IgA with total IgA), given its 3–5% prevalence among patients with iron deficiency 1

Source of Iron Loss Assessment

In men and postmenopausal women, gastrointestinal evaluation with upper and lower endoscopy is mandatory to exclude malignancy. 1 In one study, 9% of patients older than 65 years with iron deficiency had gastrointestinal cancer. 3

In premenopausal women, detailed menstrual history is essential:

• Heavy menstrual bleeding (>80 mL per cycle or >7 days duration) 1
• Gynecologic evaluation if menstrual losses appear excessive 1

Additional causes to investigate:

• Dietary insufficiency, particularly in vegetarians or restrictive diets 1
• Malabsorption disorders beyond celiac disease (inflammatory bowel disease, autoimmune gastritis, prior bariatric surgery) 2, 1
• NSAID use causing occult gastrointestinal bleeding 1
• Frequent blood donation 1
• High-impact athletic activity causing intravascular hemolysis 1

Stool guaiac testing should be performed, with positive results mandating endoscopic evaluation. 1

Treatment Algorithm

First-Line: Oral Iron Therapy

Oral iron (100–200 mg elemental iron daily) is the appropriate initial treatment for absolute iron deficiency without inflammation. 1

Optimal dosing strategy:

• Alternate-day dosing (every other day) markedly improves fractional absorption by avoiding hepcidin-mediated blockade that persists for 24 hours after each dose 1
• Administer on an empty stomach (≥1 hour before or ≥2 hours after meals) to maximize absorption 1
• Reduce elemental iron to 50–100 mg per dose; higher doses do not increase absorption and worsen gastrointestinal side effects 1

Common formulations and their elemental iron content:

• Ferrous sulfate 325 mg = 65 mg elemental iron
• Ferrous gluconate 325 mg = 38 mg elemental iron
• Ferrous fumarate 325 mg = 106 mg elemental iron

Expected response: Hemoglobin should increase by 1–2 g/dL within 4–8 weeks of therapy. 2

Indications to Switch to Intravenous Iron

Intravenous iron should be used when: 2, 1

• Gastrointestinal intolerance to oral iron (nausea, constipation, diarrhea)
• Lack of hematologic response after 4–8 weeks of adequate oral therapy
• Chronic kidney disease with eGFR <30 mL/min/1.73 m²
• Documented malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss exceeding oral replacement capacity

Available IV iron formulations: 2

• Ferric carboxymaltose (up to 1,000 mg per infusion)
• Iron sucrose (up to 200 mg per infusion)
• Low-molecular-weight iron dextran (high-dose infusion with test dose required)
• Ferric derisomaltose (up to 1,000 mg or 20 mg/kg, not to exceed 1,500 mg)

Ferric derisomaltose is the only formulation FDA-approved for total dose infusion and has demonstrated reduced cardiovascular mortality in heart failure patients. 2

Treatment Targets

After iron repletion, aim for: 1

• Ferritin ≥50 ng/mL (in the absence of inflammation) 2
• Transferrin saturation ≥20% to ensure adequate iron availability for erythropoiesis 2, 1

Monitoring Schedule

Repeat iron studies 4–8 weeks after completing oral iron therapy or 4–8 weeks after the last IV iron infusion. 2, 1 Do not measure iron parameters within 4 weeks of IV iron, as circulating iron interferes with assay accuracy. 2

If the underlying cause has been eliminated (e.g., menorrhagia treated, dietary intake corrected), a single course of iron should suffice. 2 If ongoing losses or malabsorption persist, multiple administrations will be necessary, with frequency determined by the degree of blood loss or malabsorption. 2

Critical Pitfalls to Avoid

• Do not dismiss iron deficiency based on "normal" serum iron (67 µg/dL), as serum iron exhibits high day-to-day variability and is affected by recent meals, diurnal changes, and inflammation; ferritin and transferrin saturation are far more reliable. 1
• Do not delay investigation of the underlying cause, particularly gastrointestinal evaluation in men and postmenopausal women, as malignancy must be excluded. 1, 3
• Do not continue oral iron indefinitely without reassessment; lack of response after 4–8 weeks indicates malabsorption, ongoing blood loss, or the need for IV iron. 2, 1
• Do not measure iron studies too early after IV iron (within 4 weeks), as falsely elevated results will occur. 2