From the Guidelines
Elevated iron levels with low ferritin can be caused by various conditions, including iron overload disorders, acute liver damage, certain medications, inflammatory conditions, and vitamin C deficiency. The most recent and highest quality study on this topic is from 2011 1, which provides guidance on the diagnosis and management of hemochromatosis. According to this study, serum ferritin has less biological variability than transferrin saturation (TS), but it has a significant false positive rate due to elevations related to inflammation. Some key points to consider when evaluating elevated iron levels with low ferritin include:
- Inflammatory conditions can suppress ferritin production while iron remains elevated, making it essential to assess the patient's inflammatory status 1
- Certain medications, such as estrogens, can increase serum iron while decreasing ferritin
- Vitamin C deficiency can impair iron storage as ferritin while maintaining normal or high serum iron
- Laboratory errors or timing of blood draws can affect results, as iron levels fluctuate throughout the day
- Further testing, including transferrin saturation, total iron binding capacity, and possibly genetic testing for hereditary hemochromatosis, may be necessary to determine the underlying cause of the paradoxical finding It is crucial to consider the patient's overall clinical presentation, including symptoms such as fatigue, joint pain, or skin discoloration, when evaluating elevated iron levels with low ferritin. In terms of diagnosis, the 2011 study 1 recommends using a combination of indirect markers of iron stores, including TS and serum ferritin, to identify patients with hemochromatosis. The study also notes that a serum ferritin level >250 μg/L in men and >200 μg/L in women is positive in 77% and 56%, respectively, of C282Y homozygotes. Ultimately, a thorough evaluation of the patient's clinical presentation, laboratory results, and medical history is necessary to determine the underlying cause of elevated iron levels with low ferritin and to develop an effective treatment plan.
From the Research
Elevated Iron Levels with Low Ferritin
Elevated iron levels with low ferritin can be caused by various factors, including:
- Inflammation or infection, which can increase ferritin levels as an acute-phase protein 2
- Genetic disorders, such as hemochromatosis, which can lead to iron overload and organ damage 3, 4, 5
- Secondary iron overload syndromes, which can be caused by excessive iron intake or release from erythrocytes 5
- Disturbances in iron metabolism, which can be genetic or acquired 3
Diagnosis and Management
Diagnosis of elevated iron levels with low ferritin can be challenging, and it is essential to exclude other causes of elevated ferritin, such as inflammation or liver disease 4, 5.
- Transferrin saturation and genetic testing can be used to diagnose hemochromatosis 3, 4
- Soluble transferrin receptor (sTfR) determination can be used to predict iron deficiency in patients with hemochromatosis 6
- Phlebotomy is the first-line therapy for hemochromatosis, and it can improve prognosis and prevent end-stage liver disease 5
Iron Overload and Ferritin
Iron overload can be caused by various factors, including genetic disorders, excessive iron intake, and secondary iron overload syndromes.
- Ferritin levels can be used to diagnose iron overload, but it is essential to consider other factors, such as inflammation and liver disease 2
- The diagnostic accuracy of ferritin concentrations for detecting iron deficiency and overload is variable, and it depends on the population and the threshold used 2