What is the workup for a patient with hyperferritinemia (elevated iron serum)?

From the Guidelines

The workup for a patient with hyperferritinemia should begin with a thorough history and physical examination, followed by additional laboratory tests to determine the underlying cause, including serum iron parameters such as transferrin saturation and ferritin, as recommended by the EASL clinical practice guidelines on haemochromatosis 1. The initial testing should include a complete blood count, comprehensive metabolic panel, and iron studies (serum iron, total iron-binding capacity, transferrin saturation, and ferritin).

• If hereditary hemochromatosis is suspected, genetic testing for HFE gene mutations (C282Y and H63D) should be performed.
• Transferrin saturation greater than 45% with elevated ferritin suggests iron overload disorders.
• For patients with significant hyperferritinemia (>1000 ng/mL) without obvious cause, consider inflammatory markers (CRP, ESR), liver function tests, hepatitis serologies, and screening for alcohol use disorder.
• Imaging studies such as liver ultrasound or MRI may be necessary to assess for hepatic iron deposition or other liver pathology, with MRI being 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. In cases where the diagnosis remains unclear, liver biopsy with iron quantification may be required. It's essential to recognize that elevated ferritin can result from various conditions, including hereditary hemochromatosis, inflammatory states, liver disease, malignancy, and metabolic syndrome, so the workup should be tailored to the clinical presentation and initial test results, as stated in the diagnosis and management of hemochromatosis guidelines 1. Early diagnosis of iron overload disorders is crucial as phlebotomy or chelation therapy can prevent end-organ damage to the liver, heart, and endocrine organs. The goal of treatment is to reduce tissue iron stores to normal, which can be achieved through therapeutic phlebotomy, with a target ferritin level of 50-100 lg/L, as recommended by the American Association for the Study of Liver Diseases 1.

From the Research

Workup for Elevated Iron Serum

The workup for a patient with hyperferritinemia (elevated iron serum) involves several steps to determine the underlying cause of the iron overload.

• The initial evaluation includes measuring serum iron concentration, transferrin saturation (TIBC), and serum ferritin concentration 2.
• Transferrin saturation is a useful marker for detecting iron overload, as it is elevated early in the course of the disease 2.
• Serum ferritin concentration is also a key marker, as it reflects the body's iron stores 3, 4, 5.
• Additional tests, such as liver function tests, complete blood count, and genetic testing for HFE hemochromatosis, may be necessary to determine the underlying cause of the iron overload 3, 6.
• Imaging studies, such as MRI or CT scans, may be used to assess liver iron concentration and detect any organ damage 5.
• The desferrioxamine test, liver biopsy, and quantitative phlebotomy may also be used to confirm the diagnosis of iron overload 2.

Diagnostic Considerations

• Physiological fluctuations in serum iron, liver disease, blood disorders, iron therapy, and parenchymal iron overload can all cause elevated transferrin saturation 2.
• In patients with hemochromatosis, iron depletion therapy with phlebotomy is often used to reduce iron stores, but monitoring of hemoglobin levels and serum ferritin is necessary to prevent iron deficiency 4, 6.
• Deferasirox, an iron chelator, may be used as an alternative to phlebotomy in patients with chronic anemia or other conditions that prevent phlebotomy 3, 5.

Monitoring and Treatment

• Regular monitoring of serum ferritin, transferrin saturation, and liver iron concentration is necessary to assess the effectiveness of treatment and prevent organ damage 6, 5.
• Patient compliance with phlebotomy therapy is crucial to achieve and maintain iron depletion, and regular follow-up is necessary to ensure adherence to treatment 6.
• The use of labile plasma iron and transferrin saturation in addition to serum ferritin may provide a more comprehensive assessment of iron overload in patients with different underlying anemias 5.