What is the cut-off ferritin (iron storage protein) level for diagnosing iron deficiency in adults?

Cut-off Ferritin Levels for Diagnosing Iron Deficiency in Adults

The optimal cut-off ferritin level for diagnosing iron deficiency in adults is <45 μg/L in the absence of inflammation, while in the presence of inflammation, values up to 100 μg/L may still be consistent with iron deficiency. 1

Ferritin Cut-off Values Based on Inflammatory Status

Without Inflammation:

• <15 μg/L: Highly specific (99% specificity) for iron deficiency; indicates absent iron stores 1
• <30 μg/L: Generally indicative of low body iron stores 1
• <45 μg/L: Provides optimal trade-off between sensitivity and specificity (92% specificity) for iron deficiency in clinical practice 1

With Inflammation/Chronic Disease:

• <100 μg/L: May still indicate iron deficiency due to ferritin's role as an acute phase reactant 1, 2
• >150 μg/L: Unlikely to occur with absolute iron deficiency, even with inflammation 1

Diagnostic Algorithm for Iron Deficiency

1. Measure serum ferritin

   • Primary diagnostic test with highest specificity for iron deficiency 1

2. Assess for inflammation

   • Check C-reactive protein (CRP) or other inflammatory markers
   • Review clinical status for signs of inflammation, infection, or malignancy

3. Interpret ferritin based on inflammatory status:

   • If no inflammation: Use 45 μg/L as cut-off 1
   • If inflammation present: Use 100 μg/L as cut-off 1, 2

4. Consider additional tests if results are equivocal:

   • Transferrin saturation (<20% suggests iron deficiency) 1, 2
   • Mean cell hemoglobin (MCH) - more reliable than MCV 1, 2
   • Red cell distribution width (RDW >14% suggests iron deficiency) 2
   • Serum transferrin receptor (sTfR) - not affected by inflammation 1
   • sTfR/log10 ferritin ratio (sTfR-F index) - superior discrimination in chronic disease 1

Special Considerations

Age-Specific Variations:

• Elderly population: May develop iron deficiency at higher ferritin levels (up to 100 μg/L) 3
• Children and adolescents: Lower cut-offs apply 2
  • Ages 6-12 years: 15 μg/L
  • Ages 12-15 years: 20 μg/L

Non-Anemic Iron Deficiency:

• Iron stores can be depleted (hypoferritinemia) while hemoglobin remains normal 1
• Investigation threshold should be lower in men, postmenopausal women, and those with GI symptoms or family history of GI pathology 1

Common Pitfalls to Avoid

1. Relying solely on ferritin without considering inflammatory status

   • Ferritin is an acute phase reactant and may be falsely elevated in inflammation 1, 2

2. Using outdated or inappropriate cut-off values

   • The traditional cut-off of 15-30 μg/L may miss many cases of iron deficiency 1, 4
   • Recent evidence supports higher cut-offs, especially in elderly patients 3, 5

3. Overlooking iron deficiency in normocytic anemia

   • Iron deficiency can present without microcytosis, especially in early stages or with concurrent B12/folate deficiency 1

4. Failing to investigate underlying causes

   • In men and postmenopausal women, iron deficiency warrants investigation for potential GI pathology 1

By using the appropriate ferritin cut-off values based on inflammatory status and considering additional iron parameters when necessary, clinicians can accurately diagnose iron deficiency and initiate appropriate treatment to improve patient outcomes.