From the Guidelines
Elevated ferritin levels are most commonly caused by iron overload conditions, chronic inflammation, liver disease, and certain genetic disorders, with chronic inflammation being a significant contributor, as noted in a study published in 2020 1.
Common Causes of Elevated Ferritin
The causes of elevated ferritin levels can be diverse, including:
- Iron overload conditions such as hemochromatosis
- Chronic inflammation from conditions like rheumatoid arthritis, lupus, and infections
- Liver diseases including hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease
- Certain genetic disorders
- Metabolic syndrome, characterized by obesity, diabetes, and hypertension
- Excessive alcohol consumption
- Frequent blood transfusions
- Rare genetic conditions like hemosiderosis
- Some medications
Importance of Contextual Interpretation
It is crucial to interpret ferritin levels in the context of the patient's specific conditions, as ferritin is an acute phase reactant, and its levels can be influenced by underlying inflammatory states and chronic kidney disease, as highlighted in a study from 2020 1.
Diagnostic Approach
When elevated ferritin is detected, further testing is typically needed to determine the underlying cause, considering ferritin's role as both an iron storage protein and an inflammatory marker. The diagnostic approach may involve assessing parameters such as transferrin saturation, transferrin receptor concentrations, and inflammatory markers like CRP and ESR, as discussed in a 2013 study 1.
Treatment Considerations
Treatment depends on identifying and addressing the specific cause of elevated ferritin rather than simply lowering ferritin levels. This may involve managing underlying inflammatory conditions, treating iron overload or deficiency, and addressing liver disease or other contributing factors. The goal is to improve morbidity, mortality, and quality of life outcomes by targeting the root cause of elevated ferritin levels.
From the Research
Common Causes of Elevated Ferritin Levels
Elevated ferritin levels can be caused by a variety of conditions, including:
- 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 elevated ferritin levels had malignancy 2
- Iron-overload syndromes: Iron-overload syndromes, such as hemochromatosis, can also cause elevated ferritin levels, with one study finding that 136 out of 627 patients with elevated ferritin levels 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 2
- Liver disease: Liver disease, including alcoholic and non-alcoholic liver diseases, can also cause elevated ferritin levels, with one study finding that serum ferritin was increased in 64 out of 111 patients with alcoholic liver disease and 30 out of 137 patients with non-alcoholic liver disease 3
- Infection: Infection can also cause elevated ferritin levels, with one study finding that interferon-alpha therapy reduced serum ferritin levels in a patient with chronic hepatitis C and liver hemosiderosis 4
Less Common Causes of Elevated Ferritin Levels
Less common causes of elevated ferritin levels include:
- Hemophagocytic lymphohistiocytosis/macrophage activation syndrome: This is a rare condition that can cause elevated ferritin levels, with one study finding that 6 out of 627 patients with elevated ferritin levels had this condition 2
- Anemia of chronic inflammation: This is a condition that can cause elevated ferritin levels, with one study finding that 7 out of 627 patients with elevated ferritin levels had anemia of chronic inflammation 2
- Metabolic syndrome: This is a condition that can cause elevated ferritin levels, with one study recommending that investigation of elevated serum ferritin involve identifying metabolic syndrome as a causative factor 5
Investigation of Elevated Ferritin Levels
Investigation of elevated ferritin levels involves:
- Excluding hereditary haemochromatosis: This can be done using the HFE gene test and iron studies 5
- Identifying alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection or inflammation as causative factors: This can be done through a variety of tests and examinations, including liver function tests, imaging studies, and biopsies 5
- Referral to a specialist: If serum ferritin is >1000 µg/L or if the cause of elevated serum ferritin is still unclear, referral to a gastroenterologist, haematologist or physician with an interest in iron overload is appropriate 5