{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:29:56Z","timestamp":1788056996949,"version":"build-2784847793"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Radioactive iodine (RAI) therapy is a cornerstone treatment for Graves\u2019 hyperthyroidism (GH), yet failure rates remain significant due to the complexity of individual patient responses. Traditional fixed-dose or simple calculated-dose methods often fail to account for non-linear interactions among clinical features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed data from 1,292 GH patients who received initial RAI therapy between June 2018 and July 2024. Comprehensive pre-treatment clinical, laboratory, and imaging data, including age, gender, FT4, 3-hour radioactive iodine uptake (RAIU 3h), thyroid weight, and thyroid receptor antibodies (TRAb), were collected. Stepwise regression with the Akaike Information Criterion (AIC) was employed for feature selection, identifying nine optimal predictors. Six machine learning algorithms were compared, with performance evaluated using AUC, Brier score, and Decision Curve Analysis (DCA). SHapley Additive exPlanations (SHAP) analysis provided model interpretability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The final cohort, comprising 1,292 patients (61.3% female, median age 37 years), achieved a 75.8% remission rate. Nine significant variables were identified as optimal predictors: gender, age, history of antithyroid drug use, disease course over 2 years, total iodine dose (TID), free thyroxine (FT4), RAIU 3h, thyroid weight, and TRAb. Among the algorithms tested, the Random Forest (RF) model demonstrated superior performance, achieving an AUC of 0.950 on the independent test set and a Brier score of 0.067, indicating excellent discrimination and calibration. SHAP analysis confirmed RAIU 3h, FT4, age, and thyroid weight as the most influential features, providing clinical transparency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The developed interpretable machine learning framework offers a precise, personalized tool for predicting RAI outcomes, potentially guiding optimizing dosing strategies to reduce treatment failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1711029","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T05:40:59Z","timestamp":1769406059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["From data to decision: an interpretable machine learning model for optimizing RAI therapy in Graves\u2019 hyperthyroidism"],"prefix":"10.3389","volume":"16","author":[{"given":"Lu","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyun","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhou","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehua","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1510030","article-title":"Graves\u2019 Disease","volume":"375","author":"Smith","year":"2016","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202004070","article-title":"Hyperthyroidism","volume":"172","author":"McDermott","year":"2020","journal-title":"Ann Intern Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0801880","article-title":"Clinical practice","volume":"358","author":"Brent","year":"2008","journal-title":"Graves\u2019 disease. N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20160418","article-title":"Radioiodine therapy versus antithyroid drugs in Graves\u2019 disease: a meta-analysis of randomized controlled trials","author":"Wang","year":"2016","journal-title":"Br J Radiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0229","article-title":"2016 american thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis","volume":"26","author":"Ross","year":"2016","journal-title":"Thyroid"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.20452\/pamw.16763","article-title":"Hyperthyroidism in Graves\u2019 disease: practical advice on the choice of treatment and indications for radioiodine use","volume":"134","author":"Szczepanek-Parulska","year":"2024","journal-title":"Pol Arch Intern Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020805","article-title":"A randomized comparison of radioiodine doses in Graves\u2019 hyperthyroidism","volume":"88","author":"Leslie","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7863867","article-title":"Response to radioiodine therapy for thyrotoxicosis: disparate outcomes for an indigenous population","volume":"2016","author":"Tamatea","year":"2016","journal-title":"Int J Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0286","article-title":"Clinical outcomes after estimated versus calculated activity of radioiodine for the treatment of hyperthyroidism: systematic review and meta-analysis","volume":"161","author":"de Rooij","year":"2009","journal-title":"Eur J Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1089\/thy.1998.8.393","article-title":"Observer variation in the clinical and laboratory evaluation of patients with thyroid dysfunction and goiter","volume":"8","author":"Jarl\u00f8v","year":"1998","journal-title":"Thyroid"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30149-4","article-title":"Big data and machine learning algorithms for health-care delivery","volume":"20","author":"Ngiam","year":"2019","journal-title":"Lancet Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.382228","article-title":"Machine learning applications in stroke medicine: advancements, challenges, and future prospectives","volume":"19","author":"Daidone","year":"2024","journal-title":"Neural Regener Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000768","article-title":"Machine learning, artificial intelligence and the prediction of dementia","volume":"35","author":"Merkin","year":"2022","journal-title":"Curr Opin Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12081208","article-title":"MLP-PSO hybrid algorithm for heart disease prediction","volume":"12","author":"Al Bataineh","year":"2022","journal-title":"J Pers Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1182597","article-title":"State of the art review on machine learning and artificial intelligence in the study of neonatal necrotizing enterocolitis","volume":"11","author":"McElroy","year":"2023","journal-title":"Front Pediatr"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38731","article-title":"Early heart disease prediction using feature engineering and machine learning algorithms","volume":"10","author":"Bouqentar","year":"2024","journal-title":"Heliyon"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02482-6","article-title":"Machine learning for genetics-based classification and treatment response prediction in cancer of unknown primary","volume":"29","author":"Moon","year":"2023","journal-title":"Nat Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31721-0","article-title":"An artificial intelligence-enabled ECG algorithm for the identification of patients with atrial fibrillation during sinus rhythm: a retrospective analysis of outcome prediction","volume":"394","author":"Attia","year":"2019","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597","article-title":"MissForest\u2014non-parametric missing value imputation for mixed-type data","author":"Stekhoven","year":"2012","journal-title":"Bioinformatics."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/aisy.202400304","article-title":"A perspective on explainable artificial intelligence methods: SHAP and LIME","volume":"7","author":"Salih","year":"2025","journal-title":"Advanced Intelligent Syst"},{"key":"B21","first-page":"1","article-title":"Explainable AI (XAI): Explained","author":"Reddy","year":"2023"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1159\/000517174","article-title":"The efficacy and short- and long-term side effects of radioactive iodine treatment in pediatric graves\u2019 Disease: A systematic review","volume":"10","author":"Lutterman","year":"2021","journal-title":"Eur Thyroid J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1030","article-title":"Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome","volume":"33","author":"Bonnema","year":"2012","journal-title":"Endocr Rev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7150\/ntno.64141","article-title":"Radiotheranostics - precision medicine in nuclear medicine and molecular imaging","volume":"6","author":"Duan","year":"2022","journal-title":"Nanotheranostics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.14341\/ket20106348-53","article-title":"Predictors of the results of radioiodine therapy of Gagves\u2019 disease","volume":"6","author":"Shestakova","year":"2010","journal-title":"Clin Exp thyroidology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1097\/MNM.0000000000000770","article-title":"Prognostic factor analysis in 325 patients with Graves\u2019 disease treated with radioiodine therapy","volume":"39","author":"Yang","year":"2018","journal-title":"Nucl Med Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/7535093","article-title":"Predictive factors for the efficacy of radioactive iodine treatment of graves\u2019 Disease","volume":"2024","author":"Feng","year":"2024","journal-title":"Int J Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12902-020-00557-w","article-title":"Predictive factors for early hypothyroidism following the radioactive iodine therapy in Graves\u2019 disease patients","volume":"20","author":"Hu","year":"2020","journal-title":"BMC Endocr Disord"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.47102\/annals-acadmedsg.V48N6p181","article-title":"High thyroid stimulating receptor antibody titre and large goitre size at first-time radioactive iodine treatment are associated with treatment failure in graves\u2019 Disease","volume":"48","author":"Tay","year":"2019","journal-title":"Ann Acad Med Singap"},{"key":"B30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1385\/ENDO:25:1:55","article-title":"Radioiodine treatment of hyperthyroidism","volume":"25","author":"Erem","year":"2004","journal-title":"Endocr"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-013-9895-0","article-title":"Predictors of long-term remission in patients with Graves\u2019 disease: a single center experience","volume":"44","author":"Anagnostis","year":"2013","journal-title":"Endocrine"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj1954.38.429","article-title":"Thyrotropin receptor antibody activities significantly correlate with the outcome of radioiodine (131I) therapy for hyperthyroid graves\u2019 Disease","volume":"38","author":"Kaise","year":"1991","journal-title":"Endocrinol Japon"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4103\/ejode.ejode_5_18","article-title":"Predictors of recurrent thyrotoxicosis in a cohort of Egyptian thyrotoxic patients treated with radioactive iodine","volume":"4","author":"Wafa","year":"2018","journal-title":"Egypt J Obes Diabetes Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1097\/MNM.0000000000000285","article-title":"Factors influencing the success of radioiodine therapy in patients with Graves\u2019 disease","volume":"36","author":"\u0160filigoj","year":"2015","journal-title":"Nucl Med Commun"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1568699","article-title":"Effects of metabolic and organ function factors on the efficacy of radioactive iodine therapy for hyperthyroidism","volume":"16","author":"Hu","year":"2025","journal-title":"Front Endocrinol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.15406\/emij.2016.03.00070","article-title":"Outcomes following fixed dose radioactive iodine therapy (RAI) in hyperthyroid patients with grave\u2019s disease and toxic nodular disease","volume":"3","author":"Cheah","year":"2016","journal-title":"Endocrinol Metab Int J"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04385.x","article-title":"Adjuvant lithium improves the efficacy of radioactive iodine treatment in Graves\u2019 and toxic nodular disease","volume":"77","author":"Martin","year":"2012","journal-title":"Clin Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.eswa.2019.05.028","article-title":"A comparison of random forest variable selection methods for classification prediction modeling","volume":"134","author":"Speiser","year":"2019","journal-title":"Expert Syst Appl"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.5114\/aoms\/135594","article-title":"Prediction of prognosis and survival of patients with gastric cancer by a weighted improved random forest model: an application of machine learning in medicine","volume":"18","author":"Xu","year":"2021","journal-title":"Arch Med Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7708\/ijtte.2016.6(3).10","article-title":"MULTIMODAL CHOICE MODELING USING RANDOM FOREST DECISION TREES","volume":"6","author":"Sekhar","year":"2016","journal-title":"IJTTE"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.31083\/j.fbl2703101","article-title":"Machine learning on thyroid disease: a review","volume":"27","author":"Lee","year":"2022","journal-title":"Front Biosci (Landmark Ed)"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.1109\/Confluence47617.2020.9058102","article-title":"Prediction of thyroid disorders using advanced machine learning techniques","author":"Duggal","year":"2020"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s13369-020-05206-x","article-title":"Performance analysis of machine learning algorithms for thyroid disease","volume":"46","author":"Abbad Ur Rehman","year":"2021","journal-title":"Arab J Sci Eng"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0b013e3182817c78","article-title":"High failure rates after 131I therapy in graves hyperthyroidism patients with large thyroid volumes, high iodine uptake, and high iodine turnover","volume":"38","author":"De Jong","year":"2013","journal-title":"Clin Nucl Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0000000000000152","article-title":"Response rate and factors affecting the outcome of a fixed dose of RAI-131 therapy in Graves\u2019 disease: a 10-year Egyptian experience","volume":"35","author":"El-Kareem","year":"2014","journal-title":"Nucl Med Commun"},{"key":"B46","article-title":"Personalization of radioiodine treatment for Graves\u2019 disease: a prospective, randomized study with a novel method for calculating the optimal 131I-iodide activity based on target reduction of thyroid mass","volume":"56","author":"Orsini","year":"2012","journal-title":"Q J Nucl Med Mol Imaging"},{"key":"B47","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1097\/MNM.0000000000001138","article-title":"The success rate of radioactive iodine therapy for Graves\u2019 disease in iodine-replete area and affecting factors: a single-center study","volume":"41","author":"Park","year":"2020","journal-title":"Nucl Med Commun"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1711029\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T05:41:05Z","timestamp":1769406065000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1711029\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":47,"alternative-id":["10.3389\/fendo.2025.1711029"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1711029","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"article-number":"1711029"}}