What is the primary cause of elevated Ferritin (iron storage protein) levels?

From the Guidelines

The primary cause of ferritin elevation is often multifactorial, but iron overload and inflammation are the most common underlying causes, as ferritin acts as an acute phase reactant and can rise in response to various conditions, including hereditary hemochromatosis, multiple blood transfusions, chronic liver disease, infection, autoimmune disorders, or malignancy. According to the most recent and highest quality study, 1, elevated ferritin can indicate increased tissue iron concentrations but is also non-specific, with alternative causes including inflammatory and neoplastic conditions.

When evaluating elevated ferritin, it's essential to check other iron parameters (transferrin saturation, serum iron) to distinguish between true iron overload and inflammatory causes. The study by 1 highlights the importance of non-invasive assessment of tissue iron overload by MRI, which can guide diagnosis and management, particularly in patients without homozygosity for p.C282Y and/or the presence of additional risk factors for hepatic iron overload.

Key points to consider in the evaluation of ferritin elevation include:

• Inflammation is a common cause of elevated ferritin, as it acts as an acute phase reactant
• Iron overload can result from hereditary hemochromatosis, multiple blood transfusions, or chronic liver disease
• Alcoholic liver disease, metabolic syndrome, and certain medications can also increase ferritin levels
• MRI can be useful in assessing tissue iron overload and guiding diagnosis and management
• Treatment depends on the underlying cause, ranging from phlebotomy for hemochromatosis to addressing the primary inflammatory condition, as supported by the study 1.

It's crucial to note that ferritin levels above 300 ng/mL in men or 200 ng/mL in women warrant further investigation to determine the specific cause and appropriate management, as suggested by the study 1. However, the most recent study 1 provides the most up-to-date guidance on the evaluation and management of ferritin elevation.

From the Research

Causes of Ferritin Elevation

• The primary cause of ferritin elevation can be due to various conditions, including iron overload disorders, chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions 2, 3.
• Iron overload disorders, such as hereditary hemochromatosis, can lead to elevated ferritin levels due to increased total body iron stores 2, 4.
• Other causes of hyperferritinemia include hematologic disorders, such as thalassemia syndromes, myelodysplastic syndrome, and sickle cell disease 2.
• Infections, liver dysfunction, renal failure, and hematological malignancy can also cause elevated ferritin levels 3.

Diagnosis and Investigation

• Serum ferritin level is a useful indicator of total body iron stores, but its correlation with body iron burden is not very strong 4.
• The investigation of a raised serum ferritin level should include serum transferrin saturation, liver function tests, and other relevant investigations to determine the underlying cause 5.
• Genetic testing for hereditary hemochromatosis should be considered in patients with elevated ferritin levels and a family history of the condition 2.

Clinical Significance

• Hyperferritinemia can be associated with multiple underlying causes, and the level of serum ferritin can be determined by the underlying conditions to a certain extent 3.
• Elevated ferritin levels can be a marker of iron overload, inflammation, or other underlying conditions, and its investigation and management are crucial to prevent long-term complications 5.