What is the initial workup for elevated ferritin levels in a 37-year-old male?

From the Guidelines

For an elevated ferritin in a 37-year-old male, the initial workup should include a comprehensive history, physical examination, and targeted laboratory tests, starting with serum iron parameters, including transferrin saturation and serum ferritin, as recommended by the EASL clinical practice guidelines on haemochromatosis 1. The workup should aim to distinguish between true iron overload conditions like hemochromatosis and secondary causes such as alcoholic liver disease, viral hepatitis, metabolic syndrome, or inflammatory conditions.

• Key laboratory tests include:
  • Complete blood count
  • Liver function tests
  • Iron studies, including serum iron, total iron binding capacity, and transferrin saturation
  • HFE gene testing for hereditary hemochromatosis, particularly the C282Y and H63D mutations
  • Hepatitis B and C serologies
  • Alcohol use assessment
  • Evaluation for metabolic syndrome with lipid panel, fasting glucose, and hemoglobin A1c
  • Inflammatory markers like C-reactive protein and erythrocyte sedimentation rate The concentration of serum iron and transferrin or total iron binding capacity can provide additional information for the differential diagnosis, although measuring hepcidin is not recommended 1. If ferritin is markedly elevated (>1000 ng/mL) or transferrin saturation is high (>45%), referral to a hepatologist or hematologist is appropriate, as early diagnosis is crucial, especially for hemochromatosis, to prevent complications like cirrhosis, diabetes, and cardiomyopathy 1.

From the Research

Initial Workup for Elevated Ferritin

To approach a case of elevated ferritin in a 37-year-old male, the following steps can be considered:

• Evaluate the patient's medical history, including any symptoms such as joint pain, fever, or rash, as marked hyperferritinemia can indicate severe underlying conditions 2, 3
• Order laboratory tests, including:
  • Transferrin saturation to assess iron overload 4, 5
  • Liver function tests (e.g., ALT, AST) to evaluate liver health 5
  • HFE gene mutation testing to rule out hereditary hemochromatosis 4
  • Complete blood count and blood smear to assess for hematological abnormalities
• Consider imaging studies, such as abdominal ultrasonography, to evaluate liver morphology and rule out non-alcoholic fatty liver disease 4
• If necessary, perform a liver biopsy to assess liver iron concentration and rule out other liver conditions 4, 5

Differential Diagnoses

The differential diagnoses for elevated ferritin in a 37-year-old male include:

• Hemochromatosis 4
• Non-alcoholic fatty liver disease 4
• Inflammatory conditions, such as adult-onset Still's disease 2, 3
• Infections, such as sepsis 2
• Malignancies, such as lymphoma 2
• Metabolic syndrome 4

Clinical Interpretation

The clinical interpretation of ferritin levels is crucial in identifying and managing underlying conditions. Marked hyperferritinemia requires thorough investigation to differentiate between potential underlying conditions 2. A diagnostic approach that considers the patient's history, laboratory results, and imaging studies can help guide the workup and management of elevated ferritin 5.