From the Guidelines
Hemochromatosis (Iron Overload) evaluation typically starts with the assessment of serum iron parameters, including transferrin saturation and serum ferritin.
Key Evaluation Steps
- The first step in testing for haemochromatosis is the assessment of serum iron parameters, which should include transferrin saturation and serum ferritin 1.
- Biochemical findings that indicate haemochromatosis with iron overload include elevated transferrin saturation, high ferritin, and elevated liver transaminases 1.
- MRI can be helpful for detection, non-invasive quantification of iron, and to study the distribution of iron in the liver, spleen, pancreas, heart, and brain in patients with suspicion or diagnosis of iron overload disorder 1.
- Cardiac MRI can be used to diagnose cardiac iron overload, which is useful in identifying when therapy is indicated, and serial imaging can measure response to medical therapy 1.
Important Considerations
- Transferrin saturation shows significant variability, which limits its usefulness, and blood samples for the measurement of transferrin saturation should be taken in the morning, but fasting does not improve diagnostic utility 1.
- Ferritin is not only a marker of iron overload but also an acute phase reactant, tumor marker, and indicator of increased angiogenesis, and serum ferritin concentrations are often elevated in conditions associated with fatty liver disease, such as excess alcohol consumption, or the metabolic syndrome 1.
- Genetic testing should be performed if haemochromatosis is suspected, especially with a known family history of haemochromatosis, and individuals with a positive first-degree family history of haemochromatosis should also be tested by HFE genotyping with appropriate genetic counselling 1.
From the Research
Evaluation of Hemochromatosis (Iron Overload)
The evaluation of hemochromatosis, also known as iron overload, involves a combination of laboratory tests and diagnostic procedures. The following are some of the key steps involved in the evaluation of hemochromatosis:
- Measurement of serum transferrin saturation and ferritin level to detect possible iron overload 2, 3, 4, 5, 6
- HFE genotyping to confirm the diagnosis of hereditary hemochromatosis, particularly for the C282Y and H63D mutations 2, 3, 4, 5, 6
- Magnetic resonance imaging (MRI) with quantitative assessment of iron content or liver biopsy to measure hepatic iron concentration or total iron burden 2, 4, 6
- Consideration of secondary causes of iron overload, such as hematologic disorders, iatrogenic causes, or chronic liver diseases, if HFE genetic testing is negative 2
- Evaluation for causes of hyperferritinemia, such as chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, if iron overload has been excluded 2
Diagnostic Criteria
The diagnostic criteria for iron overload disorders can be classified based on different criteria, including:
- Route of access of iron within the organism (enteral, parenteral, or placental) 5
- Predominant tissue site of iron accumulation (parenchymal or reticuloendothelial storage areas) 5
- Cause of the overload (primary or secondary) 5
- Clinical data, high transferrin saturation, and/or serum ferritin values 5
Laboratory Evaluation
The clinical laboratory plays a significant role in case finding, diagnostic validation, and monitoring of hemochromatosis therapy. Laboratory tests that may be used to evaluate hemochromatosis include: