{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:37:42Z","timestamp":1776933462532,"version":"3.51.2"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003062","name":"Erciyes University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Long-term antithyroid drug (ATD) therapy is often required in pediatric Graves\u2019 disease, yet adherence can be challenging. Therefore, identifying reliable predictors of remission and relapse is crucial for optimizing disease management. This study aimed to evaluate the role of the baseline FT3\/FT4 ratio in predicting remission and relapse, alongside other potential markers, including TRAb levels, thyroid volume, and body mass index (BMI). This retrospective, single-center study included pediatric patients diagnosed with Graves\u2019 disease and treated with ATDs. Age, sex, BMI, thyroid volume, TRAb, FT3, and FT4 levels were recorded at diagnosis, and the FT3\/FT4 ratio was calculated. Remission was defined as maintaining euthyroidism for at least 12\u00a0months after discontinuation of ATD therapy, whereas relapse was defined as the recurrence of hyperthyroidism following remission. A total of 55 patients were evaluated. The remission rate was 43.6%, and among those who achieved remission, the relapse rate was 8.3%. No significant association was found between remission and age, sex, BMI, ATD duration, or the FT3\/FT4 ratio. However, remission was significantly more likely in patients with TRAb levels\u2009&lt;\u200910\u00a0IU\/L (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Additionally, an inverse relationship was observed between thyroid volume and the likelihood of remission. Although the baseline FT3\/FT4 ratio did not predict remission, it was significantly higher in patients who experienced relapse. An FT3\/FT4 ratio\u2009&gt;\u20090.54\u00a0pmol\/pmol predicted relapse with 75% sensitivity and 98% specificity (AUC\u2009=\u20090.842;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.048).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusion<\/jats:italic>\n                    : The baseline FT3\/FT4 ratio demonstrated limited value in predicting remission but proved to be a strong indicator of relapse risk in pediatric Graves\u2019 disease. Additionally, lower TRAb levels (&lt;\u200910\u00a0IU\/L) and smaller thyroid volumes were associated with higher remission rates. Together, these findings suggest that incorporating the FT3\/FT4 ratio, TRAb levels, and thyroid volume into routine assessment may enhance risk stratification and support more personalized treatment approaches for pediatric Graves\u2019 disease.\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td align=\"left\">\n                              <jats:bold>What is Known:<\/jats:bold>\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td align=\"left\">\n                              \u2022\n                              <jats:italic>Pediatric Graves\u2019 disease often requires long-term antithyroid drug therapy, and remission rates are variable; TRAb levels and thyroid volume are recognized predictors of remission.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td align=\"left\">\n                              <jats:bold>What is New:<\/jats:bold>\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td align=\"left\">\n                              \u2022\n                              <jats:italic>The baseline FT3\/FT4 ratio has limited value in predicting remission but may serve as a strong predictor of relapse, with a ratio 0.54 pmol\/pmol showing high specifi city for relapse in pediatric Graves\u2019 disease.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-026-06808-7","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:37:29Z","timestamp":1773135449000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of the FT3\/FT4 ratio in predicting remission and relapse in pediatric Graves\u2019 disease"],"prefix":"10.1007","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-9222","authenticated-orcid":false,"given":"Leyla","family":"Kara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7708-3498","authenticated-orcid":false,"given":"Ulku Gul","family":"Siraz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5652-1401","authenticated-orcid":false,"given":"Dilek","family":"Cicek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7355-5408","authenticated-orcid":false,"given":"Emre","family":"Sarikaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7655-2301","authenticated-orcid":false,"given":"Ebru","family":"Gok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-5317","authenticated-orcid":false,"given":"Ugur","family":"Berber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-3628","authenticated-orcid":false,"given":"Mustafa","family":"Kendirci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-0128","authenticated-orcid":false,"given":"Selim","family":"Kurto\u011flu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0991-6539","authenticated-orcid":false,"given":"Nihal","family":"Hatipoglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"issue":"3","key":"6808_CR1","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/ped4.12219","volume":"4","author":"Y Gu","year":"2020","unstructured":"Gu Y et al (2020) Clinical features and predictors of remission in children under the age of 7 years with Graves\u2019 disease. Pediatr Investig 4(3):198\u2013203","journal-title":"Pediatr Investig"},{"key":"6808_CR2","doi-asserted-by":"publisher","first-page":"e481","DOI":"10.1542\/peds.2007-1535","volume":"121","author":"NS Glaser","year":"2008","unstructured":"Glaser NS, Styne DM (2008) Predicting the likelihood of remission in children with Graves\u2019 disease: a prospective, multicenter study. Pediatrics 121:e481\u2013e488","journal-title":"Pediatrics"},{"issue":"4","key":"6808_CR3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1297\/cpe.2025-0022","volume":"34","author":"K Shimura","year":"2025","unstructured":"Shimura K et al (2025) Utility of the FT3-to-FT4 ratio as a screening marker for pediatric Graves\u2019 disease. Clin Pediatr Endocrinol 34(4):213\u2013218","journal-title":"Clin Pediatr Endocrinol"},{"issue":"10","key":"6808_CR4","doi-asserted-by":"publisher","first-page":"3817","DOI":"10.1210\/jc.2008-0842","volume":"93","author":"F Kaguelidou","year":"2008","unstructured":"Kaguelidou F et al (2008) Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment. J Clin Endocrinol Metab 93(10):3817\u20133826","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"6808_CR5","doi-asserted-by":"publisher","first-page":"182","DOI":"10.4274\/jcrpe.4526","volume":"9","author":"K Demir","year":"2017","unstructured":"Demir K, \u00d6zen S, Konak\u00e7\u0131 E, Ayd\u0131n M, Darendeliler F (2017) A comprehensive online calculator for pediatric endocrinologists: \u00c7EDD \u00e7\u00f6z\u00fcm\/TPEDS metrics. J Clin Res Pediatr Endocrinol 9(2):182\u2013184. https:\/\/doi.org\/10.4274\/jcrpe.4526","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"2","key":"6808_CR6","doi-asserted-by":"publisher","first-page":"164","DOI":"10.4274\/jcrpe.galenos.2018.2018.0210","volume":"11","author":"\u0130 Esen","year":"2019","unstructured":"Esen \u0130 et al (2019) Management of thyrotoxicosis in children and adolescents: a Turkish multi-center experience. J Clin Res Pediatr Endocrinol 11(2):164\u2013172","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"5","key":"6808_CR7","first-page":"e60829","volume":"16","author":"H Almutairi","year":"2024","unstructured":"Almutairi H et al (2024) Unveiling promising modalities and enhancing patient outcomes in Graves\u2019 disease treatment: a systematic review and meta-analysis. Cureus 16(5):e60829","journal-title":"Cureus"},{"issue":"11","key":"6808_CR8","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1089\/thy.2019.0085","volume":"29","author":"G Sj\u00f6lin","year":"2019","unstructured":"Sj\u00f6lin G et al (2019) The long-term outcome of treatment for Graves\u2019 hyperthyroidism. Thyroid 29(11):1545\u20131557","journal-title":"Thyroid"},{"key":"6808_CR9","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1510030","volume":"375","author":"TJ Smith","year":"2016","unstructured":"Smith TJ, Heged\u00fcs L (2016) Graves\u2019 disease. N Engl J Med 375:1552\u20131565","journal-title":"N Engl J Med"},{"key":"6808_CR10","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.4158\/EP161350.OR","volume":"22","author":"F Magri","year":"2016","unstructured":"Magri F et al (2016) Gender influences the clinical presentation and long-term outcome of Graves disease. Endocr Pract 22:1336\u20131342","journal-title":"Endocr Pract"},{"key":"6808_CR11","first-page":"1249","volume":"16","author":"L Gru\u00f1eiro-Papendieck","year":"2003","unstructured":"Gru\u00f1eiro-Papendieck L, Chiesa A, Finkielstain G, Heinrich JJ (2003) Pediatric Graves\u2019 disease: outcome and treatment. J Pediatr Endocrinol Metab 16:1249\u20131255","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"6","key":"6808_CR12","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1111\/cen.14869","volume":"98","author":"D Puttawong","year":"2023","unstructured":"Puttawong D et al (2023) Long-term outcomes of anti-thyroid drug treatment in childhood-onset Graves\u2019 disease. Clin Endocrinol (Oxf) 98(6):823\u2013831","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"1","key":"6808_CR13","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1210\/jc.2011-1944","volume":"97","author":"J L\u00e9ger","year":"2012","unstructured":"L\u00e9ger J et al (2012) Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves\u2019 disease: national long-term cohort study. J Clin Endocrinol Metab 97(1):110\u2013119","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"6808_CR14","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1530\/EJE-14-0959","volume":"172","author":"J Harvengt","year":"2015","unstructured":"Harvengt J et al (2015) Triiodothyronine-predominant Graves\u2019 disease in childhood: detection and therapeutic implications. Eur J Endocrinol 172(6):715\u2013723","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"6808_CR15","first-page":"15","volume":"60","author":"M Minasyan","year":"2020","unstructured":"Minasyan M et al (2020) FT3:FT4 ratio in Graves\u2019 disease - correlation with TRAb level, goiter size and age of onset. Folia Med Cracov 60(2):15\u201327","journal-title":"Folia Med Cracov"},{"issue":"4","key":"6808_CR16","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1515\/jpem-2018-0495","volume":"32","author":"E Bayramo\u011flu","year":"2019","unstructured":"Bayramo\u011flu E, Elmaogullar\u0131 S, Sagsak E, Aycan Z (2019) Evaluation of long-term follow-up and methimazole therapy outcomes of pediatric Graves\u2019 disease: a single-center experience. J Pediatr Endocrinol Metab 32(4):341\u2013346","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"4","key":"6808_CR17","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.3892\/etm.2016.3058","volume":"11","author":"L Liu","year":"2016","unstructured":"Liu L, Lu H, Liu Y, Liu C, Xun C (2016) Predicting relapse of Graves\u2019 disease following treatment with antithyroid drugs. Exp Ther Med 11(4):1453\u20131458","journal-title":"Exp Ther Med"},{"issue":"15","key":"6808_CR18","doi-asserted-by":"publisher","first-page":"1487490","DOI":"10.3389\/fendo.2024.1487490","volume":"28","author":"P Yao","year":"2024","unstructured":"Yao P, Xie Y, Wang Y, Liang C, Huang B (2024) Comparison between thyroid stimulating immunoglobulin and TSH-receptor antibodies in the diagnosis and management of Graves\u2019 disease. Front Endocrinol (Lausanne) 28(15):1487490","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"6808_CR19","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ejim.2011.02.006","volume":"22","author":"DC Matthews","year":"2011","unstructured":"Matthews DC, Syed AA (2011) The role of TSH receptor antibodies in the management of Graves\u2019 disease. Eur J Intern Med 22(3):213\u2013216","journal-title":"Eur J Intern Med"},{"issue":"1","key":"6808_CR20","doi-asserted-by":"publisher","first-page":"e210073","DOI":"10.1530\/ETJ-21-0073","volume":"11","author":"CF Mooij","year":"2022","unstructured":"Mooij CF et al (2022) 2022 European thyroid association guideline for the management of pediatric Graves\u2019 disease. Eur Thyroid J 11(1):e210073","journal-title":"Eur Thyroid J"},{"issue":"2019","key":"6808_CR21","first-page":"5945178","volume":"3","author":"J Karmisholt","year":"2019","unstructured":"Karmisholt J, Andersen SL, Bulow-Pedersen I, Carl\u00e9 A, Krejbjerg A, Nygaard B (2019) Predictors of \u0131nitial and sustained remission in patients treated with antithyroid drugs for Graves\u2019 hyperthyroidism: the RISG study. J Thyroid Res 3(2019):5945178","journal-title":"J Thyroid Res"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-06808-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-026-06808-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-06808-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T07:41:32Z","timestamp":1776930092000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-026-06808-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["6808"],"URL":"https:\/\/doi.org\/10.1007\/s00431-026-06808-7","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"23 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki. Approval was obtained from the Erciyes University Clinical Research Ethics Committee approval number 2022\/629, 14.09.2022.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"172"}}