From the Guidelines
Elevated ferritin levels can result from several conditions, with iron overload disorders being the most common cause, and a thorough diagnostic workup including transferrin saturation, liver function tests, and inflammatory markers is necessary to determine the underlying cause and guide appropriate treatment. The causes of elevated ferritin levels are diverse and can be broadly categorized into several groups:
- Iron overload disorders, such as hemochromatosis, which is a genetic disorder causing excessive iron absorption, frequently leading to high ferritin 1.
- Inflammatory conditions like rheumatoid arthritis, lupus, and other autoimmune diseases can raise ferritin as part of the acute phase response 1.
- Liver diseases including hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease often show elevated ferritin due to liver cell damage releasing stored ferritin 1.
- Certain cancers, particularly leukemia, lymphoma, and breast cancer, may increase ferritin production 1.
- Frequent blood transfusions can cause iron overload as each unit of blood contains approximately 200-250 mg of iron 1.
- Metabolic syndrome, characterized by obesity, insulin resistance, and hypertension, is associated with higher ferritin levels 1.
- Rare conditions like Still's disease and hemophagocytic lymphohistiocytosis can cause extremely high ferritin 1.
- Even excessive alcohol consumption and certain medications can impact ferritin levels 1. When ferritin is elevated, additional testing like transferrin saturation, liver function tests, and inflammatory markers can help determine the underlying cause and guide appropriate treatment 1. Some key points to consider in the diagnostic workup of elevated ferritin levels include:
- The use of cutoff values for serum ferritin level and transferrin saturation to guide case-finding and diagnosis 1.
- The importance of considering the patient's clinical context, including the presence of inflammatory conditions or liver disease, when interpreting ferritin levels 1.
- The potential for genetic testing to aid in the diagnosis of hereditary hemochromatosis, but also the need for careful consideration of the risks and benefits of such testing 1.
From the Research
Causes of Elevated Ferritin
Elevated ferritin levels can be caused by a variety of conditions, including:
- Inflammatory conditions such as adult-onset Still's disease, systemic juvenile idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome 2
- Malignancy, which was the most frequent condition associated with elevated ferritin levels in one study 2
- Iron-overload syndromes, which were the second most common condition associated with elevated ferritin levels in the same study 2
- Anemia of chronic inflammation 2
- Infections 3
- Chronic liver disease 4
- Kidney failure 4
- Rheumatic conditions, such as rheumatoid arthritis and vasculitis 3
- Hematologic disorders, such as thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency 4
- Iatrogenic causes, such as multiple blood transfusions 4
- Cardiovascular conditions, such as heart failure 5
- Endocrinological conditions 5
- Autoimmune conditions 5
Diagnostic Considerations
When evaluating elevated ferritin levels, it is essential to consider the underlying cause and to rule out other potential conditions 6, 4, 3, 5. This may involve:
- Laboratory tests, such as complete blood counts, liver function tests, and inflammatory markers 2, 3
- Imaging studies, such as magnetic resonance imaging or liver biopsy 4
- Genetic testing, such as HFE genetic testing for hereditary hemochromatosis 6, 4
- Clinical evaluation, including medical history and physical examination 2, 3, 5
Clinical Implications
Elevated ferritin levels can have significant clinical implications, including: