From the Guidelines
High iron and high ferritin levels are most commonly caused by hereditary hemochromatosis, chronic alcohol consumption, inflammation, cell necrosis, tumors, non-alcoholic fatty liver disease (NAFLD), and/or the metabolic syndrome. According to the EASL clinical practice guidelines for HFE hemochromatosis 1, it is estimated that in over 90% of outpatients with hyperferritinemia, one of these causes can be identified.
Common Causes of Hyperferritinemia
- Chronic alcohol consumption
- Inflammation (check for CRP)
- Cell necrosis (check for AST, ALT and CK)
- Tumors (ESR, CT scan)
- Non-alcoholic fatty liver disease (NAFLD) and/or the metabolic syndrome (check for blood pressure, BMI, cholesterol, triglycerides, and serum glucose)
The diagnosis of HFE hemochromatosis should not be based on C282Y homozygosity alone, but requires evidence of increased iron stores 1. Patients presenting with increased serum ferritin concentrations should be searched for common causes of hyperferritinemia before genetic tests are carried out. If the patient is a C282Y homozygote, the diagnosis of HFE-HC can be established, but for all other genotypes, confounding cofactors, compensated iron loading anemia, or non-HFE hemochromatosis should be considered 1.
Diagnostic Approach
- Measure serum iron, ferritin, and transferrin saturation
- Check for CRP, AST, ALT, and CK to rule out inflammation and cell necrosis
- Consider genetic testing or liver biopsy if necessary
- Evaluate family members for evidence of iron overload if the patient has an unclear presentation 1
From the Research
Causes of High Iron and High Ferritin
- Hereditary hemochromatosis (HH) is a genetic disorder that can cause high iron and high ferritin levels due to increased intestinal iron absorption 2, 3, 4
- Iron overload secondary to hereditary hemochromatosis can lead to high ferritin levels, which can be reduced with treatment such as deferasirox 2, 3
- Other factors such as obesity and alcohol consumption can compound the risk of liver injury in people with hereditary haemochromatosis, potentially leading to high iron and ferritin levels 4
- Heterozygous β-thalassaemia can also contribute to iron overload and high ferritin levels, especially in patients with hereditary haemochromatosis 5
Treatment and Management
- Phlebotomy is the first-line therapy for hereditary hemochromatosis and can help reduce iron and ferritin levels 2, 6, 4
- Deferasirox is an alternative treatment option for patients with iron overload secondary to hereditary hemochromatosis, especially for those who are intolerant or refractory to phlebotomy 2, 3
- Desferrioxamine (DFO) can also be used to treat iron overload in selected cases where phlebotomy is not possible 6