What does an elevated ferritin level indicate?

Interpretation of Elevated Ferritin Levels

Elevated ferritin levels can indicate multiple conditions including iron overload disorders, inflammatory conditions, malignancy, liver disease, or metabolic syndrome, and require systematic evaluation to determine the underlying cause. 1

Diagnostic Thresholds and Initial Interpretation

• Iron overload suspicion thresholds:

  • Men: >300 μg/L
  • Women: >200 μg/L 1

• Ferritin level interpretation:

  • <30 μg/L: Iron deficiency (without inflammation)
  • 30-100 μg/L: Possible iron deficiency or anemia of chronic disease (with inflammation)

  • 100 μg/L: Anemia of chronic disease or iron overload

  • 1000 μg/L: Requires specialist referral and thorough evaluation 1

Common Causes of Elevated Ferritin

1. Non-iron overload conditions (90% of cases) 2:

   • Inflammatory conditions
   • Infections (viral, bacterial)
   • Malignancy (most common cause of markedly elevated ferritin >1000 μg/L) 3
   • Liver disease
   • Metabolic syndrome
   • Obesity
   • Diabetes
   • Alcohol consumption

2. Iron overload disorders (10% of cases) 2:

   • Hereditary hemochromatosis
   • Transfusional iron overload
   • Ineffective erythropoiesis

3. Hyperferritinemic syndromes (rare but significant):

   • Adult-onset Still's disease
   • Hemophagocytic lymphohistiocytosis/macrophage activation syndrome
   • Catastrophic antiphospholipid syndrome
   • Septic shock 4

Evaluation Algorithm for Elevated Ferritin

1. Initial workup:

   • Complete iron studies (serum iron, transferrin saturation, TIBC)
   • Liver function tests
   • Inflammatory markers (CRP, ESR)
   • Fasting glucose, lipid panel
   • Assessment of alcohol intake

2. Additional considerations:

   • In chronic inflammatory conditions: Check CRP and other inflammatory markers 1
   • In chronic kidney disease: Ferritin may not accurately reflect iron stores; consider additional tests (serum iron, transferrin saturation, soluble transferrin receptor) 1, 5

3. Referral criteria:

   • Ferritin >1000 μg/L
   • Unclear cause despite initial workup
   • Evidence of organ damage 1, 2

Clinical Pearls and Pitfalls

• Important caveat: Extremely high ferritin levels (>1000 μg/L) are most commonly associated with malignancy and infections rather than rheumatologic diseases 3

• Dual role of ferritin: Beyond being an iron storage marker, ferritin functions as an acute phase reactant and may have direct pathogenetic roles in inflammatory conditions 4, 6

• Misleading levels in special populations:

  • In hemodialysis patients, ferritin may be elevated due to inflammation independent of iron status 5
  • During active inflammation, ferritin levels may not accurately reflect iron stores 1

• COVID-19 connection: Severely elevated ferritin has been identified as a marker of poor prognosis in COVID-19, potentially placing it within the spectrum of hyperferritinemic syndromes 4

Management Considerations

• For iron overload: Consider therapeutic phlebotomy or iron chelation therapy based on cause and severity
• For non-iron overload conditions: Treatment should target the underlying cause
• Specialist referral (hematology, gastroenterology) is recommended for ferritin >1000 μg/L 1, 2