Small comparative study links elevated hepcidin to untreated Graves’ disease in children

Children with newly diagnosed, untreated Graves’ disease had higher concentrations of hepcidin and ferritin, higher levels of high-sensitivity C-reactive protein and thyrotropin receptor antibodies, and lower serum iron than healthy controls in a comparative study of 42 affected children and 42 controls. The investigators reported p = 0.001 for each of these between-group differences. The research, published in BMC Pediatrics, characterized a set of biochemical differences present before treatment and did not test whether antithyroid drugs or other interventions alter these markers.

The study examined hepcidin, a protein the source describes as an acute-phase reactant and a key regulator of iron homeostasis, alongside several thyroid and inflammatory measures. Before treatment began, both groups were assessed for free thyroxine, free triiodothyronine, thyrotropin receptor antibodies, high-sensitivity C-reactive protein, iron, ferritin and hepcidin. The design compared children with newly diagnosed Graves’ disease with healthy controls rather than following the affected children over time. As a result, the findings identify baseline associations in two groups of 42 participants; they do not show how an individual child’s markers changed or how they responded to care.

Hepcidin was positively associated with several factors in the affected cohort. Its reported correlation coefficients were 0.526 with high-sensitivity C-reactive protein, 0.626 with free triiodothyronine, 0.711 with ferritin and 0.427 with thyrotropin receptor antibodies. The corresponding p values were 0.01, 0.001, 0.001 and 0.001. The largest observed correlation was therefore between hepcidin and ferritin, while the relationship with thyrotropin receptor antibodies provided the reported statistical link between hepcidin and a marker of thyroid autoimmunity. These are associations within the study population, not evidence that changes in hepcidin caused changes in thyroid function, antibody levels or iron-related measurements.

Multivariable regression analysis reported statistically significant relationships between hepcidin and all four measured factors. The reported odds ratios were 2.5 for ferritin, with a 95% confidence interval of 1.17–2.86 and p = 0.006; 2.3 for thyrotropin receptor antibodies, with a 95% confidence interval of 1.16–2.74 and p = 0.008; 4.3 for high-sensitivity C-reactive protein, with a 95% confidence interval of 1.19–8.22 and p = 0.003; and 3.5 for free triiodothyronine, with a 95% confidence interval of 1.47–3.57 and p = 0.001. Although the abstract describes these model results as confirming the correlations, the supplied findings do not establish the direction of causation. They do not demonstrate that hepcidin drives inflammation or hyperthyroidism, or that either condition produces the elevated hepcidin concentration.

Overall, the results show that elevated hepcidin in untreated pediatric Graves’ disease accompanied higher ferritin, inflammation-related and antibody measurements, alongside lower serum iron. The pattern is compatible with the study’s focus on a possible association between hepcidin and disease activity, but its biological meaning remains unresolved. The sample was small, consisting of 42 newly diagnosed children and 42 healthy controls, and all measurements were obtained before treatment. The study also cannot determine whether altered hepcidin is a cause or a consequence of the disease process. The authors therefore called for further studies to clarify that relationship. Until those studies provide clearer evidence, the findings should be interpreted as a measured association in children with newly diagnosed Graves’ disease rather than a demonstrated cause, prognosis or treatment target.

Subject of Research: Hepcidin and iron-status measurements in children with untreated newly diagnosed Graves’ disease

Article Title: Assessment of hepcidin and iron status in children with untreated newly diagnosed graves’ hyperthyroidism

Article References: Metwalley, K. A., Farghaly, H. S., Shalaby, A. M., Saied, G. M., Hassan, M. A., Saleh, N. A. M., & Youssef, M. A. M. (2026). Assessment of hepcidin and iron status in children with untreated newly diagnosed graves’ hyperthyroidism. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07407-z

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07407-z

Keywords: pediatric Graves’ disease, hepcidin, iron homeostasis, serum iron, ferritin, thyroid autoimmunity, C-reactive protein, thyrotropin receptor antibodies, hyperthyroidism, Assessment, iron, status