From the Guidelines
Hyperferritinemia is most commonly caused by inflammation, metabolic disorders, and neoplastic conditions, rather than iron overload.
Causes of Hyperferritinemia
- Inflammatory conditions, such as chronic alcohol consumption, cell necrosis, and tumors 1
- Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and the metabolic syndrome 1
- Neoplastic conditions, such as hepatocellular carcinoma 1
- Iron overload disorders, including hemochromatosis, particularly in patients homozygous for the C282Y mutation in the HFE gene 1
- Other causes, such as increased alcohol consumption, and chronic liver disease 1 In patients with hyperferritinemia, it is essential to search for common causes of hyperferritinemia before genetic tests are carried out 1. Elevated ferritin levels can indicate increased tissue iron concentrations, but are also non-specific and can be caused by various conditions. Therefore, serum iron parameters alone are often insufficient to ascertain iron overload, and further evaluation, such as MRI or liver biopsy, may be necessary to confirm the diagnosis 1.
From the Research
Causes of Hyperferritinemia
The causes of hyperferritinemia, or elevated ferritin levels, can be diverse and include:
- Inflammatory conditions such as adult-onset Still's disease, systemic juvenile idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome 2
- Malignancy, which was found to be the most frequent condition associated with hyperferritinemia in one study 2
- Iron-overload syndromes, which were the second most common cause of hyperferritinemia in another study 2
- Chronic transfusion, liver disease, and hematologic malignancy, which were found to be common causes of hyperferritinemia in a study of 65,536 serum ferritin levels 3
- Infection, macrophage activation syndrome, and primary and secondary hemophagocytic lymphohistiocytosis (HLH) 3
- Autosomal dominant forms of hyperferritinemia due to mutations in the L-ferritin IRE or in A helix of L-ferritin gene 4
- Unexplained isolated hyperferritinemia without iron overload, which may be due to increased cellular ferritin secretion and/or decreased serum ferritin clearance 4
- Multiple blood transfusions, malignant disease, hepatic disease, and suspected Still's disease, which were found to be causes of extreme hyperferritinaemia in an audit study 5
- Non-human immunodeficiency virus infection, solid tumor, liver dysfunction, renal failure, and hematological malignancy, which were found to be common causes of hyperferritinemia in a retrospective study of medical records 6
Conditions Associated with Hyperferritinemia
Various conditions can lead to hyperferritinemia, including:
- Inflammatory and autoimmune disorders 2, 3
- Malignant diseases, such as hematologic malignancy and solid tumors 2, 3, 6
- Iron-overload syndromes 2
- Liver disease, including hepatic dysfunction and liver failure 3, 5, 6
- Renal failure 6
- Infections, including non-human immunodeficiency virus infection 6
- Macrophage activation syndrome and hemophagocytic lymphohistiocytosis (HLH) 3
- Genetic disorders, such as autosomal dominant forms of hyperferritinemia 4