What is the best approach to manage a patient with low iron saturation (16%) and ferritin (25) and significant fatigue, but normal hemoglobin (14)?

Management of Iron Deficiency Without Anemia

Oral iron supplementation is strongly recommended for this patient with iron deficiency (ferritin 25 ng/mL, transferrin saturation 16%) and significant fatigue despite normal hemoglobin (14 g/dL). 1, 2

Diagnosis Confirmation

• The patient has iron deficiency without anemia, characterized by:
  • Low ferritin (25 ng/mL) - below the diagnostic threshold of 30 ng/mL 2
  • Low transferrin saturation (16%) - below the diagnostic threshold of 20% 1
  • Normal hemoglobin (14 g/dL) 2
  • Significant fatigue symptoms despite normal hemoglobin 3

Treatment Approach

First-Line Treatment:

• Oral iron supplementation at 100-200 mg elemental iron daily, in divided doses 1
  • Ferrous sulfate 325 mg (containing approximately 65 mg elemental iron) once or twice daily 2
  • Consider alternate-day dosing for better absorption and fewer gastrointestinal side effects 1

Monitoring:

• Reassess iron parameters (ferritin, transferrin saturation) after 8-10 weeks of treatment 1
• Target ferritin level should be >50 μg/L to effectively reduce fatigue symptoms 3

Alternative Approach (if oral iron fails):

• If patient experiences gastrointestinal intolerance (constipation, diarrhea, nausea) or shows inadequate response after 8-10 weeks 1
• Consider intravenous iron administration using one of the newer carbohydrate-bound formulations 1

Evidence for Treatment in Non-Anemic Iron Deficiency

• Randomized controlled trials have demonstrated that iron supplementation significantly improves fatigue in non-anemic women with low ferritin levels 4, 3
• In one study, fatigue decreased by 47.7% in the iron group versus 28.8% in the placebo group (p=0.02) 3
• The benefit appears to be limited to those with ferritin levels ≤50 μg/L 4

Clinical Considerations

• Iron deficiency without anemia can cause significant symptoms including fatigue, irritability, depression, difficulty concentrating, and exercise intolerance 2
• Symptoms may occur at ferritin levels <100 ng/mL, but treatment is most beneficial when levels are <50 ng/mL 5, 3
• While investigating the cause of iron deficiency is important (menstrual bleeding, gastrointestinal blood loss, malabsorption), treatment should not be delayed 2, 5

Common Pitfalls to Avoid

• Failing to recognize and treat iron deficiency in the absence of anemia 2, 3
• Using hemoglobin alone to guide iron therapy decisions 1
• Waiting for anemia to develop before initiating treatment 5, 3
• Not addressing the underlying cause of iron deficiency while providing supplementation 5
• Inadequate duration of treatment - iron stores need time to replenish 1