1. Overview
Ferritin is a vital intracellular protein found in almost all cells of the body and functions as the primary storage form of iron. It is a macromolecule with an average molecular weight of approximately 440 kDa, which varies depending on its iron content. The majority of ferritin-bound iron is stored in the liver, spleen, and bone marrow.
A small amount of ferritin circulates in the blood, and serum ferritin levels correlate closely with total body iron stores. Because of this relationship, ferritin measurement is a key laboratory marker for evaluating iron metabolism and diagnosing disorders related to iron deficiency or iron overload.
2. Symptoms
Ferritin itself does not cause symptoms; rather, clinical manifestations are related to conditions associated with abnormal ferritin levels. Low ferritin levels are commonly associated with iron deficiency and may be linked to symptoms such as fatigue, weakness, restless legs syndrome, or burning sensations in the legs.
Elevated ferritin levels may be seen in iron overload states or inflammatory conditions and can be associated with symptoms related to liver disease, chronic inflammation, autoimmune disorders, malignancies, or systemic inflammatory syndromes such as adult-onset Still disease.
3. Causes
Abnormal ferritin levels arise due to disturbances in iron balance or inflammatory states. Decreased ferritin levels are most commonly caused by iron deficiency anemia, chronic blood loss (e.g., gastrointestinal bleeding), malabsorption syndromes, pregnancy, adrenal insufficiency, liver cirrhosis, hypothyroidism, and chronic kidney disease.
Increased ferritin levels may be seen in iron overload conditions such as hemochromatosis and hemosiderosis, repeated blood transfusions, chronic inflammation, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, infections such as tuberculosis, liver disease (including hepatitis and non-alcoholic fatty liver disease), obesity, and insulin resistance.
Ferritin is an acute-phase reactant, meaning it increases during inflammation or infection regardless of actual iron stores.
4. Risk Factors
Risk factors for abnormal ferritin levels include chronic inflammatory diseases, liver disorders, renal disease, autoimmune conditions, malignancies, and a history of repeated blood transfusions. Individuals with hereditary hemochromatosis are at risk for markedly elevated ferritin levels due to excessive iron absorption.
Low ferritin levels are more common in individuals with poor dietary iron intake, chronic blood loss, malabsorption, pregnancy, and chronic illnesses. Interpretation of ferritin levels must consider age, sex, inflammatory status, and associated laboratory markers such as serum iron, total iron-binding capacity (TIBC), and transferrin saturation.
5. Prevention and Clinical Management
Ferritin testing plays a central role in the diagnosis and monitoring of iron-related disorders. Indications for testing include evaluation of iron deficiency anemia, monitoring iron therapy, assessment of iron overload states (including hemochromatosis and hemosiderosis), evaluation of liver disease, restless legs syndrome, adult-onset Still disease, and monitoring chronic conditions such as cancer, renal disease, and autoimmune disorders.
No special patient preparation is required prior to sample collection. Blood samples are typically collected in a plain tube, and serum is separated and sent to the laboratory promptly. Plasma samples collected in EDTA or lithium heparin tubes are also acceptable.
Ferritin levels can be measured using several laboratory techniques, including chemiluminescent immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay, nephelometry, turbidimetry, and radioimmunoassay.
Reference ranges vary by age and sex, with higher values generally observed in adult males and older individuals. Interpretation of ferritin levels requires correlation with other iron studies. For example, iron deficiency anemia is characterized by low ferritin, low serum iron, and high TIBC, while anemia of chronic disease typically shows normal or elevated ferritin with low serum iron and low or normal TIBC.
During interpretation, it is essential to rule out inflammation or infection by assessing markers such as C-reactive protein, evaluating liver and renal function, reviewing recent blood transfusions or iron supplementation, and considering hereditary hemochromatosis risk. In inflammatory states, higher ferritin cut-off values may be required, and ferritin should be interpreted alongside transferrin saturation and TIBC.
Limitations of ferritin testing include false elevation in inflammatory, infectious, liver, and autoimmune disorders, reduced reliability during late pregnancy, and potential interference in patients receiving monoclonal antibody therapy.
