What is the workup for elevated iron studies, specifically hyperferritinemia (elevated ferritin) and/or hyperironemia (elevated iron)?

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From the Guidelines

The workup for elevated iron studies should begin with a comprehensive history and physical examination, followed by confirmatory laboratory tests including serum ferritin, transferrin saturation, total iron binding capacity (TIBC), and serum iron levels, as recommended by the most recent guidelines 1. The initial evaluation should focus on identifying potential causes of iron overload, such as hereditary hemochromatosis, and assessing for end-organ damage.

  • Key laboratory tests include:
    • Serum ferritin
    • Transferrin saturation
    • Total iron binding capacity (TIBC)
    • Serum iron levels
  • Additional tests may be necessary, such as liver function tests, fasting glucose, and cardiac evaluation, to assess for liver disease, diabetes, and cardiomyopathy, as these conditions are commonly associated with iron overload 1. Imaging studies, such as liver ultrasound or MRI, may be necessary to evaluate liver iron concentration and potential fibrosis, particularly in patients with suspected iron overload or hereditary hemochromatosis 1.
  • MRI is 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.
  • R2* sequences are the best validated for quantifying iron. Genetic testing for hereditary hemochromatosis, specifically the HFE gene mutations (C282Y and H63C), should be performed in patients with confirmed iron overload, as this can help identify those at risk of developing complications such as cirrhosis, diabetes, and cardiomyopathy 1. The mainstay of treatment for iron overload is therapeutic phlebotomy, which involves removing 500 mL of blood (containing approximately 200-250 mg of iron) weekly until ferritin levels normalize (usually below 50-100 ng/mL), followed by maintenance phlebotomy every 2-4 months 1.

From the Research

Workup for Elevated Iron Studies

The workup for elevated iron studies typically involves a series of tests to determine the underlying cause of the iron overload.

  • The initial evaluation may include a physical examination, medical history, and laboratory tests such as serum iron, transferrin saturation, and ferritin levels 2, 3, 4.
  • Additional tests may be ordered to rule out other conditions that can cause iron overload, such as hemochromatosis, thalassemia, or other anemias 2, 3.
  • Imaging studies such as MRI or CT scans may also be used to assess iron deposition in organs such as the liver, heart, or pancreas 4.

Treatment Options

The treatment of iron overload depends on the underlying cause and severity of the condition.

  • Phlebotomy is often the initial treatment of choice for hereditary hemochromatosis, while iron chelation therapy is used to treat transfusional siderosis and other conditions where phlebotomy is not feasible 2, 4.
  • Iron chelators such as deferoxamine, deferiprone, and deferasirox may be used to remove excess iron from the body, either alone or in combination with phlebotomy 2, 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The treatment of secondary hemochromatosis.

Deutsches Arzteblatt international, 2009

Research

Iron mobilization using chelation and phlebotomy.

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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