A 13-year-old male with low ferritin, low transferrin saturation, low serum iron, and high unsaturated iron‑binding capacity—what is the diagnosis and recommended treatment?

Iron Deficiency Anemia: Diagnosis and Treatment in a 13-Year-Old Male

This 13-year-old male has absolute iron deficiency anemia confirmed by ferritin 18 ng/mL, transferrin saturation 15%, and should be treated with oral elemental iron 3 mg/kg/day administered between meals, with repeat hemoglobin assessment in 4 weeks to confirm response. 1

Diagnostic Interpretation

The laboratory values unequivocally confirm iron deficiency:

• Ferritin 18 ng/mL is well below the diagnostic threshold of <30 ng/mL for absolute iron deficiency in the absence of inflammation, providing 100% specificity for depleted iron stores 1, 2

• Transferrin saturation 15% falls below the diagnostic cutoff of <16% for iron deficiency in adults and adolescents, indicating insufficient circulating iron available for erythropoiesis 1, 3, 4

• Serum iron 67 μg/dL is low, reflecting inadequate iron delivery to tissues 1

• UIBC 387 μg/dL is markedly elevated, demonstrating the body's compensatory increase in transferrin production to capture any available iron—a highly specific marker for empty iron stores with diagnostic accuracy of 0.80-0.97 4

The combination of low ferritin and low transferrin saturation definitively establishes absolute iron deficiency with depleted body iron stores 3, 4.

Mandatory Evaluation for Underlying Cause

Iron deficiency in a 13-year-old male requires investigation of the source, as it rarely occurs without identifiable blood loss or inadequate intake 4:

• Dietary assessment: Evaluate for restrictive diets, inadequate red meat intake, or excessive cow's milk consumption (>24 oz daily), which can displace iron-rich foods and cause occult gastrointestinal blood loss 1

• Gastrointestinal bleeding: Screen with stool guaiac testing; if positive, endoscopic evaluation is mandatory 4. Consider NSAID use, which can cause gastric erosions 4

• Malabsorption disorders: Test for celiac disease (tissue transglutaminase antibodies) and inflammatory bowel disease, particularly if growth delay, abdominal pain, or diarrhea are present 4, 2

• Athletic activity: High-impact sports can cause hemolysis and gastrointestinal blood loss ("runner's anemia") 4

• Helicobacter pylori infection: Noninvasive testing is recommended, as H. pylori is a common cause of iron deficiency anemia in adolescents 2

First-Line Treatment: Oral Iron Supplementation

Prescribe elemental iron 3 mg/kg/day administered between meals 1:

• For a typical 13-year-old male weighing 45 kg, this equals approximately 135 mg elemental iron daily (e.g., ferrous sulfate 325 mg contains 65 mg elemental iron; prescribe two tablets daily) 1

• Administer on an empty stomach (≥1 hour before or ≥2 hours after meals) to maximize absorption 4

• Counsel parents/guardians about dietary optimization: increase red meat, poultry, fish, iron-fortified cereals, and vitamin C-rich foods to enhance absorption 1

• Common adverse effects include constipation, nausea, and dark stools; approximately 50% of patients experience decreased adherence due to gastrointestinal symptoms 2

Alternative Dosing Strategy to Improve Tolerance

• Every-other-day dosing markedly improves fractional iron absorption by avoiding hepcidin-mediated blockade sustained by daily dosing, while reducing gastrointestinal side effects 4, 2

Monitoring Response and Confirming Diagnosis

Repeat hemoglobin concentration in 4 weeks 1:

• Expected response: Hemoglobin increase of ≥1 g/dL or hematocrit increase of ≥3% confirms iron deficiency anemia as the diagnosis 1, 5

• If confirmed: Continue iron treatment for 2 additional months to replenish iron stores, then recheck hemoglobin 1

• Reassess hemoglobin approximately 6 months after successful treatment completion 1

Non-Response Algorithm

If hemoglobin fails to increase by ≥1 g/dL after 4 weeks despite documented compliance and absence of acute illness 1:

1. Obtain additional laboratory tests: Mean corpuscular volume (MCV), red cell distribution width (RDW), and repeat serum ferritin 1

2. Consider alternative diagnoses:

   • Thalassemia minor: Low MCV with RDW ≤14.0% (versus iron deficiency: low MCV with RDW >14.0%) 1
   • Lead poisoning: Elevated erythrocyte protoporphyrin concentration 1
   • Chronic inflammatory disease: Ferritin >15 μg/L suggests anemia is not due to iron deficiency 1

3. Evaluate for malabsorption: Consider celiac disease testing, inflammatory bowel disease, or concurrent use of proton-pump inhibitors/H₂-blockers that impair iron absorption 4, 2

4. Assess for ongoing blood loss: Repeat stool guaiac; if positive, proceed to endoscopy 4

5. Switch to intravenous iron if oral iron is not tolerated, malabsorption is documented, or no hematologic response occurs after 4–8 weeks of adequate oral therapy 4, 2

Treatment Targets

• Hemoglobin: Normalize for age and sex (typically 13–16 g/dL for adolescent males) 1

• Ferritin: Achieve ≥30 ng/mL (without inflammation) or ≥100 ng/mL (if inflammation is present) to ensure adequate iron stores 3, 2, 6

• Transferrin saturation: Target ≥20% to confirm sufficient iron availability for erythropoiesis 3, 6

Common Pitfalls to Avoid

• Do not rely on serum iron alone: Serum iron exhibits high day-to-day variability, diurnal fluctuations, and post-prandial changes; normal serum iron does not exclude iron deficiency 1, 4

• Do not dismiss iron deficiency based on "borderline" ferritin: Ferritin <30 ng/mL is diagnostic regardless of other parameters 1, 2

• Do not overlook underlying pathology: In adolescent males, iron deficiency anemia is uncommon and mandates thorough investigation for gastrointestinal bleeding, malabsorption, or dietary insufficiency 1, 4, 2

• Do not continue oral iron indefinitely without response: If no hemoglobin increase occurs after 4 weeks, investigate non-compliance, malabsorption, ongoing blood loss, or alternative diagnoses rather than simply continuing the same regimen 1, 4