From the Guidelines
Hyperferritinemia is a significant indicator of potential iron overload and related complications, including liver disease, diabetes, and cardiac arrhythmias. The implications of hyperferritinemia are multifaceted and can be associated with various conditions, including hemochromatosis, a genetic disorder characterized by excessive iron absorption 1.
Common Causes of Hyperferritinemia
- Chronic alcohol consumption
- Inflammation
- Cell necrosis
- Tumors
- Non-alcoholic fatty liver disease (NAFLD) and/or the metabolic syndrome 1
- Hemochromatosis, particularly in individuals with C282Y homozygosity or C282Y/H63D compound heterozygosity 1
Clinical Presentation
Patients with hyperferritinemia may present with nonspecific symptoms, including:
- Fatigue
- Weakness
- Joint pain
- Abdominal pain
- Skin pigmentation
- Cardiac arrhythmias
- Impotence
- Diabetes mellitus 1
Diagnosis and Management
The diagnosis of hemochromatosis and related conditions involves the assessment of serum iron parameters, including transferrin saturation and serum ferritin 1. Phlebotomy remains the mainstay of treatment for hemochromatosis, aiming to reduce tissue iron stores to normal levels 1.
Key Considerations
- Serum ferritin levels have a significant false positive rate due to elevations related to inflammation and other non-hepatic chronic inflammatory conditions 1
- The concentration of serum iron and transferrin or total iron binding capacity can provide additional information for the differential diagnosis 1
- Genetic testing for HFE hemochromatosis should be carried out in all patients with otherwise unexplained increased serum ferritin and increased transferrin saturation 1
In clinical practice, it is essential to consider the potential implications of hyperferritinemia and to investigate common causes of hyperferritinemia before proceeding with genetic testing or other diagnostic evaluations 1.
From the Research
Implications of Hyperferritinemia
The implications of hyperferritinemia are varied and can be associated with several underlying conditions. Some of the key implications include:
- Elevated serum ferritin levels can indicate severe underlying conditions, including infections, cardiovascular diseases, endocrinological disorders, autoimmune diseases, and malignancies 2
- Hyperferritinemia can be a result of inflammation, infection, chronic iron overload, or other uncommon pathologies, including hemophagocytic lymphohistiocytosis (HLH) 3
- The presence of hyperferritinemia can have a significant impact on disease severity and prognosis, with some studies suggesting a direct linkage between high ferritin levels and poor prognosis 4
- Hyperferritinemia can be caused by a variety of conditions, including non-human immunodeficiency virus infection, solid tumors, liver dysfunction, renal failure, and hematological malignancy 5
Clinical Significance
The clinical significance of hyperferritinemia is highlighted by the following points:
- Ferritin levels should not be overlooked as merely an indicator of iron status or inflammation, as marked hyperferritinemia requires thorough investigation to differentiate between potential underlying conditions 2
- The level of serum ferritin can be determined by the underlying conditions to a certain extent, but the variation is significant, and patients with hyperferritinemia frequently have multiple conditions 5
- The decision to treat hyperferritinemia should be individualized and may be influenced by the presence of other features of iron overload 6
Diagnostic Considerations
When diagnosing hyperferritinemia, the following considerations should be taken into account:
- The positive predictive value of hyperferritinemia for HLH is quite low, and more common explanations should be considered before suspecting HLH 3
- A variety of diseases can lead to hyperferritinemia by themselves, and patients with marked hyperferritinemia mostly have multiple underlying causes 5
- The clinical interpretation of ferritin levels and appropriate diagnostic workup are essential in identifying and managing underlying conditions to reduce morbidity and mortality 2