What investigations are indicated for consistently elevated ferritin levels?

From the Guidelines

Consistently elevated ferritin levels indicate the need for further investigation to rule out haemochromatosis and other conditions.

Initial Investigations

The first step in investigating consistently elevated ferritin levels is to assess serum iron parameters, which should include:

• Transferrin saturation
• Serum ferritin 1 These tests can help identify iron overload and haemochromatosis.

Additional Tests

Additional tests that may be considered include:

• Liver function tests (e.g., AST, ALT) to evaluate liver damage
• Complete blood count (CBC) to rule out other conditions that may cause elevated ferritin levels
• C-reactive protein (CRP) to evaluate inflammation
• Imaging studies (e.g., MRI) to assess liver iron content
• Genetic testing for HFE mutations (e.g., C282Y, H63D) if haemochromatosis is suspected 1

Conditions to Rule Out

It is essential to rule out other conditions that may cause elevated ferritin levels, such as:

• Chronic alcohol consumption
• Inflammation (e.g., rheumatoid arthritis)
• Cell necrosis (e.g., liver disease)
• Tumors (e.g., hepatocellular carcinoma)
• Non-alcoholic fatty liver disease (NAFLD) and/or the metabolic syndrome 1

Clinical Evaluation

A thorough clinical evaluation, including a physical examination and medical history, is crucial to identify signs and symptoms of haemochromatosis, such as:

• Fatigue
• Joint pain
• Abdominal pain
• Skin pigmentation
• Cardiac arrhythmias
• Impotence 1 By following these steps, healthcare providers can determine the underlying cause of consistently elevated ferritin levels and develop an appropriate treatment plan.

From the Research

Investigations for Elevated Ferritin Levels

To investigate consistently elevated ferritin levels, several tests and evaluations can be considered:

• Patient history: chronic liver disease, excessive alcohol consumption, hereditary factors 2
• Clinical features: metabolic syndrome, acute or chronic inflammation, infection, malignancy 2
• Biochemical tests:
  • Ferritin 3, 4, 2, 5, 6
  • Transferrin saturation 2, 5
  • Hemoglobin 2
  • Liver enzymes 2, 5
  • CRP/SR 2
  • Phosphatidyl ethanol 2
  • Lipid profile 2
  • Glucose 2
• Imaging studies: magnetic resonance imaging (MRI) for iron determination 2
• Liver biopsy: to measure hepatic iron concentration 5

Specific Conditions to Consider

Certain conditions may be associated with elevated ferritin levels, including:

• Iron overload syndromes: hereditary hemochromatosis, dysmetabolic iron overload syndrome (DIOS), alcohol-related hemosiderosis 4, 2, 6
• Inflammatory conditions: adult-onset Still's disease, systemic juvenile idiopathic arthritis, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) 4, 6
• Malignancy 6
• Infection 4, 6
• Anemia of chronic inflammation 6

Algorithm for Investigation

An algorithm for investigating hyperferritinemia has been proposed, which considers the level of ferritin, transferrin saturation, and liver tests to determine the need for further investigation or treatment 2