What are the causes of severely elevated ferritin levels (hyperferritinemia)?

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From the Guidelines

Ferritin levels over 1000 ng/mL are most commonly caused by iron overload disorders, such as hereditary hemochromatosis, and can also be elevated in chronic liver diseases, inflammatory conditions, metabolic syndrome, and certain cancers. The causes of ferritin over 1000 ng/mL can be multifactorial, including:

  • Iron overload disorders like hereditary hemochromatosis, where genetic mutations lead to excessive iron absorption 1
  • Frequent blood transfusions, which can accumulate iron in the body
  • Chronic liver diseases, such as alcoholic liver disease, hepatitis, and non-alcoholic fatty liver disease, which can cause liver inflammation and impaired iron metabolism
  • Inflammatory conditions, like rheumatoid arthritis, lupus, and certain infections, which can raise ferritin as part of the acute phase response
  • Metabolic syndrome, characterized by obesity, diabetes, and hypertension, which is increasingly recognized as a cause of hyperferritinemia
  • Rare conditions, like Still's disease and hemophagocytic lymphohistiocytosis, which can cause extremely high ferritin levels
  • Certain cancers, particularly leukemia, lymphoma, and breast cancer, which may elevate ferritin It is essential to consult with a healthcare provider promptly for proper evaluation, which typically includes additional blood tests, genetic testing for hemochromatosis, and possibly liver imaging or biopsy to determine the underlying cause and appropriate treatment 1.

From the Research

Causes of Ferritin Over 1000

The causes of ferritin levels over 1000 can be varied and complex. Some of the possible causes include:

  • Malignancy: Studies have shown that malignancy is a common cause of elevated ferritin levels, with one study finding that 153 out of 627 patients with ferritin levels over 1000 had malignancy 2.
  • Iron-overload syndromes: Iron-overload syndromes, such as hereditary hemochromatosis, can also cause elevated ferritin levels, with one study finding that 136 out of 627 patients with ferritin levels over 1000 had iron-overload syndromes 2.
  • Inflammatory conditions: Inflammatory conditions, such as adult-onset Still's disease, systemic juvenile idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome, can also cause elevated ferritin levels, with one study finding that 6 out of 627 patients with ferritin levels over 1000 had these conditions 2.
  • Infection: Non-human immunodeficiency virus infection is also a common cause of hyperferritinemia, with one study finding that it was the most frequent cause of hyperferritinemia in a general hospital 3.
  • Liver dysfunction: Liver dysfunction can also cause elevated ferritin levels, with one study finding that it was a common cause of hyperferritinemia in a general hospital 3.
  • Renal failure: Renal failure can also cause elevated ferritin levels, with one study finding that it was a common cause of hyperferritinemia in a general hospital 3.
  • Hematological malignancy: Hematological malignancy can also cause elevated ferritin levels, with one study finding that it was a common cause of hyperferritinemia in a general hospital 3.
  • Porphyria cutanea tarda: Porphyria cutanea tarda is a unique iron-related disorder that can cause elevated ferritin levels, with one study finding that it was associated with hereditary hemochromatosis and hepatocellular carcinoma 4, 5, 6.

Other Possible Causes

Other possible causes of ferritin levels over 1000 include:

  • Anemia of chronic inflammation: One study found that 7 patients with ferritin levels over 1000 had anemia of chronic inflammation 2.
  • Unknown causes: In some cases, the cause of elevated ferritin levels may be unknown, with one study finding that 5 out of 627 patients with ferritin levels over 1000 had no clearly definable cause for hyperferritinemia 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Causes and significance of markedly elevated serum ferritin levels in an academic medical center.

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2013

Research

Hyperferritinemia: causes and significance in a general hospital.

Hematology (Amsterdam, Netherlands), 2018

Research

Porphyria cutanea tarda: a unique iron-related disorder.

Hematology. American Society of Hematology. Education Program, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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