Abstract
Objective: Differentiating Graves disease (GD) from Hashitoxicosis in children is often challenging due to overlapping clinical and biochemical features at presentation. This study aimed to evaluate the diagnostic utility of commonly available clinical and biochemical parameters to support etiologic classification in pediatric autoimmune thyrotoxicosis.
Materials and Methods: We retrospectively analyzed 58 children aged 0–18 years diagnosed with autoimmune thyrotoxicosis between 2019 and 2025. Clinical, laboratory, and imaging findings were compared between patients with GD and Hashitoxicosis. Receiver operating characteristic (ROC) analysis and logistic regression were performed to assess the diagnostic performance of key parameters.
Results: The cohort was female-predominant, with similar sex distribution between groups (34/44, 77.3% in GD vs 11/14, 78.6% in Hashitoxicosis). Palpitations were the most common presenting symptom (17, 29.3 %). Incidental detection occurred in 17 (29.3%), of whom 9 (52.9%) had subtle symptoms identified on detailed clinical evaluation. Ophthalmopathy was observed exclusively in GD (13, 29.5%). fT3 levels and the fT3/fT4 ratio were significantly higher in GD than in Hashitoxicosis (p = 0.002 and p = 0.001, respectively). TRAb showed the highest diagnostic performance (AUC = 0.950), followed by fT3 (AUC = 0.856) and the fT3/fT4 ratio (AUC = 0.809). A TRAb cut-off of 2.6 IU/L yielded 75% sensitivity and 100% specificity, whereas fT3 ≥6 pg/mL yielded 93% sensitivity and 46% specificity. Anti-TPO and anti-Tg antibodies showed poor discriminatory value. TRAb remained independently associated with GD (OR = 3.61, p = 0.011). Nine children with Hashitoxicosis (64.3%) were managed without treatment and achieved spontaneous resolution.
Conclusion: Differentiating GD from Hashitoxicosis requires an integrated assessment of clinical features, antibody status, and hormone dynamics. TRAb remains the most informative marker, while fT3 and the fT3/fT4 ratio may provide complementary value. Anti-thyroid antibodies have limited utility for etiologic differentiation. Accurate classification helps guide the management and avoid unnecessary treatment.
References
- Esen İ, Bayramoğlu E, Yıldız M, et al. Management of thyrotoxicosis in children and adolescents: a Turkish multi-center experience. J Clin Res Pediatr Endocrinol. 2019; 11: 164-72. https://doi.org/10.4274/jcrpe.galenos.2018.2018.0210
- Metwalley KA, Farghaly HS. Graves’ disease in children: an update. Clin Med Insights Endocrinol Diabetes. 2023; 16: 11795514221150615. https://doi.org/10.1177/11795514221150615
- Williamson S, Greene SA. Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland. Clin Endocrinol (Oxf). 2010; 72: 358-63. https://doi.org/10.1111/j.1365-2265.2009.03717.x
- Rodanaki M, Lodefalk M, Forssell K, et al. The incidence of childhood thyrotoxicosis is increasing in both girls and boys in Sweden. Horm Res Paediatr. 2019; 91: 195-202. https://doi.org/10.1159/000500265
- Soliman A, Alyafei F, Ahmed S, et al. Pediatric hyperthyroidism and its therapeutic outcomes: a comparative review of Graves’ disease, Hashimoto’s thyroiditis, and hashitoxicosis. Int J Sci Res Arch. 2025; 16: 824-37. https://doi.org/10.30574/ijsra.2025.16.1.2086
- Wasniewska M, Corrias A, Salerno M, et al. Outcomes of children with hashitoxicosis. Horm Res Paediatr. 2012; 77: 36-40. https://doi.org/10.1159/000334640
- Kilci F, Sarıkaya E, Özcan Murat N, et al. Epidemiological, clinical, laboratory, and radiological characteristics of children and adolescents with Hashimoto’s thyroiditis: a single-center experience. Turk Arch Pediatr. 2024; 59: 567-73. https://doi.org/10.5152/TurkArchPediatr.2024.24174
- Nabhan ZM, Kreher NC, Eugster EA. Hashitoxicosis in children: clinical features and natural history. J Pediatr. 2005; 146: 533-6. https://doi.org/10.1016/j.jpeds.2004.10.070
- Mooij CF, Cheetham TD, Verburg FA, et al. 2022 European Thyroid Association guideline for the management of pediatric Graves’ disease. Eur Thyroid J. 2022; 11: e210073. https://doi.org/10.1530/ETJ-21-0073
- Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016; 26: 1343-421. https://doi.org/10.1089/thy.2016.0229
- Neyzi O, Bundak R, Gökçay G, et al. Reference values for weight, height, head circumference, and body mass index in Turkish children. J Clin Res Pediatr Endocrinol. 2015; 7: 280-93. https://doi.org/10.4274/jcrpe.2183
- World Health Organization. Goitre as a determinant of the prevalence and severity of iodine deficiency disorders in populations [Internet]. 2014 Available at: https://iris.who.int/bitstream/handle/10665/133706/WHO_NMH_NHD_EPG_14.5_eng.pdf;sequence=1.
- Acuna OM, Athannassaki I, Paysse EA. Association between thyroid-stimulating immunoglobulin levels and ocular findings in pediatric patients with Graves disease. Trans Am Ophthalmol Soc. 2007; 105: 146-51.
- World Health Organization. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. [Internet]. 2017 Available at: https://www.who.int/publications/i/item/9789241595827.
- Kourime M, McGowan S, Al Towati M, et al. Long-term outcome of thyrotoxicosis in childhood and adolescence. Arch Dis Child. 2017;archdischild-2017-313454. https://doi.org/10.1136/archdischild-2017-313454
- Kocabey Sütçü Z, Selver Eklioğlu B, Atabek ME. Hyperthyroidism in pediatric patients: ten years of experience. J Pediatr Acad. 2024. https://doi.org/10.4274/jpea.2024.277
- Yıldırım E, Esen İ, Ökdemir D. Demographic and clinical characteristics of childhood autoimmune thyroiditis. J Pediatr Res. 2025; 12: 90-95. https://doi.org/10.4274/jpr.galenos.2025.30676
- Kırmızıbekmez H, Yeşiltepe Mutlu RG, Dursun F, et al. Atypical presentation of Hashimoto’s disease in an adolescent. J Clin Res Pediatr Endocrinol. 2014;6:262-5. https://doi.org/10.4274/jcrpe.1450
- Şahlı E, Gündüz K. Thyroid-associated ophthalmopathy. Turk J Ophthalmol. 2017; 47: 94-105. https://doi.org/10.4274/tjo.80688
- Cui Z, Wang Z, Liu X, et al. Establishment of clinical diagnosis model of Graves’ disease and Hashimoto’s thyroiditis. J Transl Med. 2019; 17: 11. https://doi.org/10.1186/s12967-018-1765-3
- Shimura K, Sawano K, Nagasaki K, et al. Utility of the FT3-to-FT4 ratio as a screening marker for pediatric Graves’ disease. Clin Pediatr Endocrinol. 2025; 34: 213-8. https://doi.org/10.1297/cpe.2025-0022
- Minamitani K, Sato H, Ohye H, et al. Guidelines for the treatment of childhood-onset Graves’ disease in Japan. Clin Pediatr Endocrinol. 2017; 26: 29-62. https://doi.org/10.1297/cpe.26.29
- Mooij CF, Zwaveling-Soonawala N, Hillebrand JJ, et al. Approach to the patient: challenging patients of pediatric thyrotoxicosis. J Clin Endocrinol Metab. 2025; 110: e878-e885. https://doi.org/10.1210/clinem/dgae592
- Rahhal SN, Eugster EA. Thyroid stimulating immunoglobulin is often negative in children with Graves’ disease. J Pediatr Endocrinol Metab. 2008; 21:1085-90. https://doi: 10.1515/jpem.2008.21.11.1085.
- Liu Y, Liu X, Wu N. Testing for distinguishing Hashimoto’s thyroiditis in the hyperthyroid stage and Graves’ disease. Int J Gen Med. 2023; 16: 2355-63. https://doi.org/10.2147/IJGM.S410640
- Bayramoğlu E, Elmaoğulları S, Sağsak E, et al. Long-term methimazole therapy outcomes in pediatric Graves’ disease. J Pediatr Endocrinol Metab. 2019; 32: 341-6. https://doi.org/10.1515/jpem-2018-0495
- Li P, Wang W, Yan M, et al. Methimazole treatment in children and adolescents with Graves’ disease. BMC Endocr Disord. 2023; 23: 233. https://doi.org/10.1186/s12902-023-01484-2
- Lieshout JMV, Mooij CF, Trotsenburg ASPV, et al. Methimazole-induced remission rates in pediatric Graves’ disease. Eur J Endocrinol. 2021;185:219-29. https://doi.org/10.1530/EJE-21-0077
- Wong TWC, Wong MYS. Remission in pediatric Graves’ disease treated with antithyroid drugs. Ann Pediatr Endocrinol Metab. 2022; 27: 308-314. https://doi.org/10.6065/apem.2244038.019
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