How should iron studies with hyperferritinemia (elevated ferritin), normal iron, low transferrin saturation, and normal total iron binding capacity (total iron binding capacity) be interpreted?

From the Guidelines

The pattern of hyperferritinemia with normal iron, low transferrin saturation, and normal total iron binding capacity most likely represents an acute phase reaction rather than iron overload. This biochemical profile is commonly seen in inflammatory conditions, chronic diseases, infections, or malignancies. Ferritin is an acute phase reactant that increases during inflammation, independent of iron status 1. The normal iron and normal TIBC with low transferrin saturation suggests that iron metabolism is affected by inflammation rather than by true iron excess or deficiency. Some key points to consider in the interpretation of these iron studies include:

• The role of ferritin as an acute phase reactant, which can be elevated in conditions unrelated to iron overload 1
• The importance of considering the clinical context and other laboratory findings, such as CRP and ESR, to confirm the presence of inflammation 1
• The need to investigate and address the underlying inflammatory condition, rather than pursuing iron reduction therapies like phlebotomy, which would be inappropriate in this context 1
• The potential for genetic testing for hereditary hemochromatosis, but only if other suggestive features or family history are present 1 Once the underlying inflammatory condition is treated, ferritin levels typically normalize over time. Additional testing should include C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to confirm the presence of inflammation. If inflammation is confirmed, the underlying cause should be investigated through a thorough history, physical examination, and targeted testing based on symptoms. Treatment should focus on addressing the underlying inflammatory condition rather than iron reduction therapies like phlebotomy, which would be inappropriate in this context. Genetic testing for hereditary hemochromatosis is generally not indicated with this pattern unless there are other suggestive features or family history.

From the Research

Interpretation of Iron Studies

The iron studies provided show a serum iron level of 20, ferritin of 410, iron binding capacity of 167, and transferrin saturation of 12. To interpret these results, we need to consider the relationships between these parameters and the clinical context.

Hyperferritinemia

• Elevated ferritin levels (hyperferritinemia) can indicate iron overload, but ferritin is also an acute-phase protein that increases in response to inflammation or infection 2.
• A study published in 2014 found that hyperferritinemia is predictive of iron overload only in patients with very high levels of serum ferritin (>2000 μg/L) 3.
• In this case, the ferritin level is 410, which is elevated but not extremely high.

Iron Deficiency and Overload

• Iron deficiency is typically diagnosed based on low serum ferritin levels, but in inflammatory conditions, a higher threshold of <100 μg/L may be used 2.
• Transferrin saturation (TSAT) is a marker of iron availability and can be used to confirm iron deficiency, especially in patients with inflammatory conditions 2.
• A study published in 2021 found that ferritin concentration is a reasonably sensitive and specific test for iron deficiency in people presenting for medical care, but its performance in screening asymptomatic people is uncertain 4.

Clinical Context

• The patient's iron binding capacity is normal, which suggests that the body's ability to bind and transport iron is intact.
• The transferrin saturation is low (12%), which may indicate restricted iron availability for erythropoiesis, despite the elevated ferritin level 2.
• The clinical context, including the presence of any inflammatory conditions or other underlying diseases, is crucial in interpreting these results 3, 5, 2.

Diagnosis and Management

• Based on the available evidence, it is challenging to determine whether the patient has iron overload or deficiency without more clinical information 3, 4, 5, 2.
• Further evaluation, including assessment of inflammatory markers and other clinical parameters, may be necessary to guide diagnosis and management 2.