Causes of Elevated Ferritin Levels
Elevated ferritin levels are most commonly caused by inflammation, malignancy, liver disease, and iron overload syndromes, with only about 10% of cases actually representing true iron overload. 1
Common Causes of Hyperferritinemia
Inflammatory Conditions
- Acute and chronic infections
- Autoimmune disorders
- Adult-onset Still's disease
- Systemic juvenile idiopathic arthritis
- Hemophagocytic lymphohistiocytosis/macrophage activation syndrome 2, 3
- COVID-19 (recently identified as part of hyperferritinemic syndrome) 4
Malignancies
- Various types of cancer (most frequent cause of markedly elevated ferritin >1000 μg/L) 3
- Hematologic malignancies
Iron Overload Syndromes
- Hereditary hemochromatosis
- Multiple blood transfusions
- Hemolytic anemias
- Ineffective erythropoiesis 2, 5
Liver Disease
Metabolic Conditions
- Chronic kidney disease
- Diabetes mellitus
- Metabolic syndrome 2
Other Causes
- Alcohol consumption
- Unexplained isolated hyperferritinemia (genetic variants) 6
- Anemia of chronic inflammation 3
Evaluation of Hyperferritinemia
Initial Assessment
- Check inflammatory markers (CRP, ESR)
- Assess for chronic diseases:
- Kidney function (eGFR, urinalysis, urine protein)
- Liver function tests
- Complete blood count 2
Iron Studies
- Serum iron
- Total iron binding capacity (TIBC)
- Transferrin saturation (TSAT)
- Complete iron profile to differentiate between:
- True iron overload (elevated TSAT >45%)
- Functional iron deficiency (low serum iron, low TIBC, low transferrin) 2
Interpretation of Ferritin Levels
| Ferritin Level | Interpretation |
|---|---|
| <10 μg/L | Severe iron deficiency |
| <30 μg/L | Iron deficiency without inflammation |
| 30-100 μg/L | Possible iron deficiency or anemia of chronic disease |
| 50-100 μg/L | Target maintenance range for most patients |
| >100 μg/L | Possible anemia of chronic disease or iron overload |
| >1000 μg/L | High risk of cirrhosis (20-45%) [2] |
Management Considerations
When to Refer to Specialists
- Ferritin >1000 μg/L
- Elevated TSAT >45% with suspected iron overload
- Elevated liver enzymes
- Evidence of end-organ damage (liver disease, cardiomyopathy)
- Unclear cause after initial evaluation 2
Treatment Approach
- Address underlying cause of hyperferritinemia
- Consider iron supplementation only if transferrin saturation is <20% and ferritin <800 ng/mL
- Iron chelation therapy is indicated only when:
- Ferritin >1000 ng/mL with evidence of iron overload
- Transferrin saturation >45%
- Transfusion-dependent patients
- Patients with myelodysplastic syndromes with low-risk disease 2
Lifestyle Modifications
- Weight loss for patients with NAFLD
- Regular physical activity
- Reduced consumption of processed foods and sugar
- Limited alcohol intake or abstinence
- Avoidance of iron supplements when not indicated 2
Important Clinical Pearls
- Extremely high ferritin levels (>10,000 μg/L) are rare (0.08% of ferritin requests) and most commonly associated with malignancy, multiple blood transfusions, hepatic disease, and Still's disease 5
- Ferritin is an acute phase reactant, so infection may increase serum ferritin to levels suggesting iron overload 7
- In patients with chronic kidney disease, anemia (Hgb <9 g/dL) rather than elevated ferritin is a risk factor for increased bacteremia 7
- Monitoring response to treatment requires regular assessment of hemoglobin, ferritin, and transferrin saturation every 1-3 months 2