Does a 40-year-old female with surgical menopause, hyperferritinemia (elevated ferritin), low transferrin saturation, and hypoferritinemia (low iron level) indicate functional iron deficiency and should it be treated with intravenous (IV) iron?

Functional Iron Deficiency with Elevated Ferritin: Treatment Recommendation

This patient's laboratory pattern (ferritin 317 ng/mL, transferrin saturation <15%, serum iron 59 µg/dL) indicates functional iron deficiency, and intravenous iron therapy should be considered, particularly if she is symptomatic or anemic.

Understanding the Laboratory Pattern

Your patient demonstrates the classic biochemical signature of functional iron deficiency:

• Elevated ferritin (317 ng/mL) suggests adequate iron stores in the reticuloendothelial system 1
• Low transferrin saturation (<15%) indicates insufficient iron availability for erythropoiesis 1
• Low serum iron (59 µg/dL) confirms inadequate circulating iron for red blood cell production 1

Functional iron deficiency occurs when iron cannot be mobilized quickly enough from storage sites to meet erythropoietic demands, despite adequate total body iron stores. 1 This differs from absolute iron deficiency, where total body iron stores are depleted (ferritin <100 ng/mL and TSAT <20% in most populations). 1

Diagnostic Criteria Met

The combination of ferritin 100-800 ng/mL with TSAT <20% defines functional iron deficiency across multiple guideline sources. 1 Your patient's ferritin of 317 ng/mL falls squarely within this range, and her TSAT <15% is well below the 20% threshold. 1

Critical Missing Information

Before proceeding with IV iron, you must determine:

• Hemoglobin level - This is the most important missing value 1
• Presence of symptoms (fatigue, exercise intolerance, dyspnea) 2, 3
• Evidence of inflammation - Check C-reactive protein, as inflammation can elevate ferritin and reduce TSAT independent of true iron deficiency 1
• Underlying cause - In a 40-year-old woman with surgical menopause, investigate gastrointestinal blood loss, malabsorption (celiac disease), or chronic disease 3, 4

Treatment Algorithm

If Hemoglobin is Normal and Patient is Asymptomatic:

• Oral iron supplementation may be sufficient (28-50 mg elemental iron daily or every other day) 2, 3
• Iron therapy may not be required if hemoglobin is at target despite low iron indices 1
• Recheck iron studies in 8-10 weeks 2

If Hemoglobin is Low (<12 g/dL) or Patient is Symptomatic:

• IV iron is superior to oral iron for functional iron deficiency 1
• Consider ferric carboxymaltose 750 mg IV, repeated once after 7 days (total 1,500 mg) 5
• Alternative: iron sucrose 200 mg IV weekly for 5 doses 1
• Recheck hemoglobin in 2-4 weeks and iron studies at 4-6 weeks 5, 3

If Inflammation is Present (Elevated CRP):

• A trial of IV iron (50-125 mg weekly for 8-10 doses) can help distinguish functional iron deficiency from inflammatory iron block 1
• If no erythropoietic response occurs, inflammatory block is likely and further iron should be withheld until inflammation resolves 1

Safety Considerations with Elevated Ferritin

The safety of IV iron in patients with ferritin 300-500 ng/mL is well-established. 1 The DRIVE study demonstrated that IV iron improved hemoglobin even in patients with ferritin 500-1,200 ng/mL when TSAT was <25%, though this study was not powered for safety outcomes. 1

Key safety thresholds:

• Generally safe to give IV iron when ferritin <800 ng/mL 1
• Withhold iron when ferritin >1,000 ng/mL or TSAT >50% 1
• Monitor for infusion reactions (rare with newer formulations, <1%) 3
• Organ damage from iron overload requires ferritin levels dramatically higher than seen in your patient and >20g excess iron 1

Common Pitfalls to Avoid

• Do not dismiss low TSAT simply because ferritin is elevated - this is the definition of functional iron deficiency 1
• Do not assume inflammation without checking CRP - ferritin can be elevated from iron stores alone 1, 2
• Do not use oral iron if patient has failed oral therapy previously or has severe anemia - IV iron is more effective 1, 3
• Do not continue iron supplementation indefinitely without monitoring - recheck ferritin and TSAT to avoid iron overload 1, 2

Specific Recommendation for Your Patient

Given ferritin 317 ng/mL and TSAT <15%, proceed as follows:

1. Obtain hemoglobin and CRP immediately 1, 3
2. If hemoglobin <12 g/dL or patient is symptomatic: Give IV iron (ferric carboxymaltose 750 mg, repeat once after 7 days) 5
3. If hemoglobin ≥12 g/dL and asymptomatic: Trial of oral iron 28-50 mg every other day 2, 3
4. Investigate underlying cause: Consider bidirectional endoscopy and celiac serology given her age and sex 3, 4
5. Recheck labs: Hemoglobin at 2-4 weeks, iron studies at 4-6 weeks 5, 3