From the Guidelines
Laboratory findings in hemochromatosis typically include elevated serum iron levels, increased transferrin saturation (usually >45%), and high serum ferritin concentrations (often >300 ng/mL in men and >200 ng/mL in women). These abnormalities reflect the excessive iron absorption and accumulation characteristic of this disorder. Genetic testing may reveal mutations in the HFE gene, particularly C282Y and H63D, which are commonly associated with hereditary hemochromatosis 1. Liver function tests might show elevated liver enzymes (AST, ALT) indicating hepatic damage from iron deposition. In advanced cases, blood glucose levels may be elevated due to pancreatic damage and diabetes development. Complete blood count is usually normal unless there's concurrent liver disease causing thrombocytopenia. Liver biopsy, though not always necessary for diagnosis, would show increased hepatic iron concentration and possible fibrosis or cirrhosis in advanced disease. These laboratory abnormalities result from the dysregulation of hepcidin, a hormone that controls iron absorption, leading to progressive iron overload in multiple organs.
Some key points to consider in the diagnosis of hemochromatosis include:
- Elevated transferrin saturation and serum ferritin levels are key indicators of iron overload 1
- Genetic testing for HFE gene mutations can confirm the diagnosis of hereditary hemochromatosis 1
- Liver biopsy can provide definitive evidence of iron overload and organ damage, but is not always necessary for diagnosis 1
- Early diagnosis and treatment can prevent long-term complications and improve quality of life 1
It's worth noting that the threshold levels for serum ferritin and transferrin saturation can vary, but serum ferritin level greater than 200 µg/mL and transferrin saturation greater than 55% suggest an increased risk for hereditary hemochromatosis and the need for further investigation 1. Overall, a combination of laboratory tests, genetic testing, and clinical evaluation is necessary for the accurate diagnosis and management of hemochromatosis.
From the Research
Lab Findings in Hemochromatosis
The lab findings in hemochromatosis typically include:
- Elevated serum ferritin levels 2, 3, 4
- Increased transferrin saturation 2, 3, 4
- Elevated serum iron levels 3, 4
- Decreased unsaturated iron binding capacity 4
Relationship Between Lab Findings and Iron Stores
Studies have shown that:
- Serum ferritin levels are the best predictor of body iron stores 4
- The correlation between serum ferritin levels and body iron stores is stronger in patients homozygous for the C282Y mutation than in those who are not 4
- Transferrin saturation and serum iron levels can also be used to estimate body iron stores, but are not as accurate as serum ferritin levels 3, 4
Diagnostic Approach
A diagnostic approach to hyperferritinemia with a non-elevated transferrin saturation may include:
- Measuring serum ferritin and transferrin saturation levels 5
- Testing for HFE mutations 2, 5
- Liver imaging and liver biopsy to assess liver iron concentration 5
- Using observations from a large series of patients with hepatic iron overload as a gold standard to guide the interpretation of non-invasive iron tests 5
Screening for Hereditary Hemochromatosis
Screening primary care patients for hereditary hemochromatosis with transferrin saturation and serum ferritin level may be useful, but:
- The prevalence of the disease in primary care is relatively low, ranging from 1 in 169 patients to 1 in 556 patients 6
- The diagnostic usefulness of transferrin saturation and serum ferritin level in identifying early disease is variable, and no blinded, independent comparisons of screening tests with the gold standard have been identified 6
- The benefits of screening may not outweigh the risks and costs, due to the lack of prospective data on the natural history of the disease 6