Can Hepcidin Be Measured?
Yes, hepcidin can be measured in serum and urine using standardized assays, and it serves as an emerging diagnostic tool for genetic and acquired iron metabolism disorders, though widespread clinical implementation remains limited by lack of harmonized assays and established reference values. 1
Clinical Utility of Hepcidin Measurement
Hepcidin measurement is a promising clinical tool for diagnosing and managing both genetic disorders (such as Iron Refractory Iron Deficiency Anemia/IRIDA) and acquired iron disorders including iron deficiency, iron deficiency anemia, iron loading anemias, and iron maldistribution. 1
Diagnostic Advantages Over Traditional Markers
Hepcidin provides added diagnostic value beyond ferritin alone because it integrates multiple regulatory signals: iron stores, inflammation, and erythropoiesis. 1
In patients with inflammation and increased or ineffective erythropoiesis, hepcidin levels reflect the net effect of these competing signals, whereas the relationship between hepcidin and ferritin becomes less predictable. 1
Hepcidin measurement, combined with other iron status parameters and inflammatory markers, can help predict response to oral iron therapy and guide treatment decisions when competing signals exist (anemia, iron deficiency, inflammation). 1
Available Measurement Methods
Assay Types
Competitive ELISA (c-ELISA) is the method of choice for large-scale quantification due to its low limit of detection, low cost, and high-throughput capability. 2
Mass spectrometry methods (WCX-TOF-MS and IC-TOF-MS) are available as special-purpose assays, with WCX-TOF-MS being particularly valuable for disorders with variable concentrations of hepcidin isoforms, such as chronic kidney disease, because of its specificity for bioactive hepcidin-25. 2
Both immunochemical and mass spectrometry-based methods can reliably measure hepcidin in blood and urine. 3
Hepcidin Isoforms
Hepcidin exists as three isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. 2
Only hepcidin-25 participates in iron metabolism regulation by binding to ferroportin and inducing its degradation. 2, 3
Critical Limitations in Clinical Practice
Major Barriers to Implementation
The lack of widely available harmonized and/or standardized assays for hepcidin measurement hampers determination of pediatric reference values and clinical decision limits, significantly complicating use of this parameter in routine clinical practice. 1
Specific Challenges
Implementation in pediatric practice has been particularly hampered by lack of standardized reference values for healthy children across different age groups relative to iron status. 1
Absolute hepcidin concentrations differ between measurement methods (c-ELISA vs. WCX-TOF-MS), though relative differences in median concentrations across various diseases remain similar. 2
Hepcidin isoforms contribute to measurement differences between methods, most prominently in patients with chronic kidney disease. 2
Clinical Contexts Where Hepcidin Measurement Adds Value
Iron Deficiency vs. Anemia of Chronic Disease
- Hepcidin concentrations measured by both c-ELISA and IC-TOF-MS correlate with ferritin concentrations <60 μg/L and are suitable for distinguishing between iron deficiency anemia alone versus the combination of iron deficiency anemia and anemia of chronic disease. 2
Genetic Iron Disorders
Hepcidin is suppressed in thalassemia syndromes, congenital dyserythropoietic anemia type 1, and is undetectable in juvenile hemochromatosis with HAMP mutations. 4
Hepcidin levels are significantly elevated in hemochromatosis type 4 (ferroportin disease). 4
Age-Specific Considerations
- Hepcidin levels corrected for iron indicators are relatively high in children <12 years compared to children ≥12 years, possibly reflecting adaptive responses to infection susceptibility in younger children versus growth demands in adolescents. 1
Practical Recommendations
When considering hepcidin measurement, use it in combination with traditional iron parameters (ferritin, transferrin saturation, soluble transferrin receptor) rather than as a standalone test, particularly in complex cases involving both iron deficiency and inflammation. 1
Prioritize hepcidin measurement for suspected genetic iron disorders (IRIDA, juvenile hemochromatosis, ferroportin disease) where diagnosis impacts management. 1, 4
Consider hepcidin testing to predict oral iron therapy response in patients with competing signals from inflammation and iron deficiency. 1
Recognize that standardization efforts using secondary reference material commutable to human serum/plasma are needed before widespread clinical adoption. 1