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CMAJ : Canadian Medical Association Journal logoLink to CMAJ : Canadian Medical Association Journal
. 2021 Oct 4;193(39):E1534. doi: 10.1503/cmaj.210359

Hyperferritinemia

Alexander Kumachev 1,, David W Frost 1
PMCID: PMC8568085  PMID: 34607847

Ferritin is a cellular iron storage protein and an acute phase reactant

Clinicians obtain ferritin levels when they suspect iron deficiency or overload; they may also obtain ferritin levels during the work-up of some hematologic or autoimmune conditions.14 Levels may be elevated in many chronic conditions (Box 1) or during acute illness, which can confound interpretation.2 Levels that return to normal after resolution of illness do not require further investigation.

Box 1: Causes of hyperferritinemia.14 .

• Alcohol use
• Alcoholic and nonalcoholic fatty liver disease
• Chronic kidney disease
• Hematologic causes
 • Thalassemia
 • Chronic hemolytic anemia
 • Sickle cell anemia
 • Parenteral iron overload or red blood cell transfusions
 • Myelodysplastic syndromes
• Hemochromatosis
• Infectious causes
 • Viral hepatitis
 • HIV
 • Osteomyelitis
• Inflammatory causes
 • Connective tissue disorders
 • Rheumatoid arthritis
• Metabolic syndrome
• Neoplastic causes
 • Solid organ and hematologic malignant diseases

Transferrin saturation testing can identify iron overload states

If the transferrin saturation is above 45% and ferritin levels are greater than 300 μg/L in men or than 200 μg/L in women, genetic testing should be done to assess for hemochromatosis.4 Secondary causes of iron overload (e.g., iron-loading anemias, exogenous iron administration) can also have elevated transferrin saturation. Hyperferritinemia without elevated transferrin saturation suggests an alternate cause.2,4

Ferritin elevations above 10 000 μg/L should prompt consideration of specific diagnoses

Although elevations above 10 000 μg/L may be seen in malignant disease, chronic kidney disease or liver dysfunction,35 high levels could also suggest adult-onset Still disease and hemophagocytic lymphohistiocytosis in acutely ill patients with suggestive features (e.g., fever, hepatosplenomegaly, rash, neurologic findings, pancytopenia).1,5

Patient history and examination should guide additional investigations

Further testing may include evaluating markers of inflammation and autoimmune disease, serologic evidence of infection and ultrasonography of the liver. Alcohol intake and risk factors for metabolic syndrome should also be reviewed.2,3

Patients with stable, mild ferritin elevation do not require further testing

Patients with serum ferritin levels below 1000 μg/L without an elevated transferrin saturation or clear underlying cause should be counselled about alcohol cessation and dietary changes aimed at managing metabolic syndrome. Stable repeat levels at 3–6 months do not require additional testing.2 Ferritin levels persistently above 1000 μg/L without a clear cause should be investigated further by a general internist or hepatologist.3,4

Footnotes

Competing interests: None declared.

This article has been peer reviewed.

Funding: Dr. Frost is supported by the Dr. Herbert Ho Ping Kong Chair in General Internal Medicine, University Health Network, University of Toronto.

References

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  • 2.Cullis JO, Fitzsimons EJ, Griffiths WJ, et al. Investigation and management of a raised serum ferritin. Br J Haematol 2018;181:331–40. [DOI] [PubMed] [Google Scholar]
  • 3.Adams PC, Barton JC. A diagnostic approach to hyperferritinemia with a non-elevated transferrin saturation. J Hepatol 2011;55:453–8. [DOI] [PubMed] [Google Scholar]
  • 4.Kowdley KV, Brown KE, Ahn J, et al. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol 2019;114:1202–18. [DOI] [PubMed] [Google Scholar]
  • 5.Senjo H, Higuchi T, Okada S, et al. Hyperferritinemia: causes and significance in a general hospital. Hematology 2018;23:817–22. [DOI] [PubMed] [Google Scholar]

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