{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:52Z","timestamp":1791348712500,"version":"4.3.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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>Aim<\/jats:title>\n                    <jats:p>To investigate whether the associations between Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) ultrasound features and malignancy vary according to thyroid nodule size.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This two-center retrospective cohort study included 3726 thyroid nodules, which were categorized according to maximum diameter as \u22641 cm or &amp;gt;1\u00a0cm. Extreme gradient boosting models and SHapley Additive exPlanations (SHAP) were used for exploratory visualization of the contributions of individual ultrasound features to malignancy prediction in the overall cohort and the two size subgroups. Multivariable Firth logistic regression was used to estimate the adjusted associations between the C-TIRADS features and malignancy. Single-feature interaction models were constructed to assess whether nodule size modified these associations. The discriminative performance of the original C-TIRADS model and the interaction model was compared using the area under the receiver operating characteristic curve (AUC). Center-adjusted sensitivity analyses were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Vertical orientation and solid composition showed greater contributions to malignancy prediction and stronger associations with malignancy in nodules \u22641 cm, whereas microcalcification and ill-defined\/irregular margin or extrathyroidal extension showed stronger associations with malignancy in nodules &amp;gt;1\u00a0cm. Significant feature-by-size interactions were identified for vertical orientation, solid composition, microcalcification, and ill-defined\/irregular margin or extrathyroidal extension, whereas no significant interactions were observed for markedly hypoechoic or comet-tail artifact. The interaction model showed a modest but statistically significant improvement in discriminative performance compared with the original C-TIRADS model (AUC 0.918 vs. 0.911,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). The center-adjusted sensitivity analyses yielded consistent findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The associations between C-TIRADS ultrasound features and malignancy exhibit significant size-dependent heterogeneity. In nodules \u22641 cm, vertical orientation and solid composition may indicate a substantially higher likelihood of malignancy and therefore warrant particularly careful clinical evaluation, whereas microcalcification and ill-defined\/irregular margin or extrathyroidal extension may be more informative for malignancy assessment in nodules &amp;gt;1\u00a0cm. Considering nodule size when interpreting individual C-TIRADS features may improve diagnostic discrimination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1844286","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:46:07Z","timestamp":1791348367000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Size-dependent heterogeneity in the associations of C-TIRADS ultrasound features with malignancy in thyroid nodules"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongming","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Interventional Ultrasound, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, Second Affiliated Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianying","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Second Affiliated Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, First Affiliated Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Interventional Ultrasound, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0336","article-title":"Thyroid nodule size at ultrasound as a predictor of malignancy and final pathologic size","volume":"27","author":"Cavallo","year":"2017","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2653","article-title":"The diagnostic value of the ultrasound gray scale ratio for different sizes of thyroid nodules","volume":"8","author":"Chen","year":"2019","journal-title":"Cancer Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.s313468","article-title":"The value of relative size in the ultrasound diagnosis of follicular thyroid neoplasm","volume":"14","author":"Zhang","year":"2021","journal-title":"Int J Gen Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacr.2017.01.046","article-title":"ACR thyroid imaging, reporting and data system (TI-RADS): White paper of the ACR TI-RADS committee","volume":"14","author":"Tessler","year":"2017","journal-title":"J Am Coll Radiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1159\/000478927","article-title":"European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: The EU-TIRADS","volume":"6","author":"Russ","year":"2017","journal-title":"Eur Thyroid J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2021.0713","article-title":"2021 Korean thyroid imaging reporting and data system and imaging-based management of thyroid nodules: Korean Society of Thyroid Radiology consensus statement and recommendations","volume":"22","author":"Ha","year":"2021","journal-title":"Korean J Radiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-020-02441-y","article-title":"2020 Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules: The C-TIRADS","volume":"70","author":"Zhou","year":"2020","journal-title":"Endocrine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1691092","DOI":"10.3389\/fendo.2025.1691092","article-title":"SWE, C-TIRADS and AI-assisted diagnostic systems in distinguishing thyroid nodules of different lesion size: Which has better diagnostic performance","volume":"16","author":"Zhou","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"21616","DOI":"10.1038\/s41598-021-01114-8","article-title":"Influence of lesion size on shear wave elastography in the diagnosis of benign and malignant thyroid nodules","volume":"11","author":"Li","year":"2021","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s00432-024-05895-z","article-title":"Predictive value of the single most suspicious ultrasound feature in subcentimeter thyroid nodules: A retrospective observational cohort study","volume":"150","author":"Huang","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.s461076","article-title":"Alteration trend and overlap analysis of positive features in different-sized benign and malignant thyroid nodules: Based on Chinese Thyroid Imaging Reporting and Data System","volume":"17","author":"Qu","year":"2024","journal-title":"Int J Gen Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"32118","DOI":"10.1038\/s41598-024-83888-1","article-title":"Identification of lesion location and discrimination between benign and malignant findings in thyroid ultrasound imaging","volume":"14","author":"Yang","year":"2024","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/srep43183","article-title":"Thyroid nodule sizes influence the diagnostic performance of TIRADS and ultrasound patterns of 2015 ATA guidelines: A multicenter retrospective study","volume":"7","author":"Xu","year":"2017","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2352031942","article-title":"Diagnosis of thyroid cancer in children: Value of gray-scale and power doppler US","volume":"235","author":"Lyshchik","year":"2005","journal-title":"Radiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1530\/etj-23-0067","article-title":"2023 European Thyroid Association clinical practice guidelines for thyroid nodule management","volume":"12","author":"Durante","year":"2023","journal-title":"Eur Thyroid J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1507\/endocrj.ej24-0644","article-title":"The 2024 revised clinical guidelines on the management of thyroid tumors by the Japan Association of Endocrine Surgery","volume":"72","author":"Sugitani","year":"2025","journal-title":"Endocr J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-020-02442-x","article-title":"Thyroid imaging reporting and data system (TIRADS) for ultrasound features of nodules: Multicentric retrospective study in China","volume":"72","author":"Zhou","year":"2020","journal-title":"Endocrine"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.938961","article-title":"Diagnostic performance of C-TIRADS in malignancy risk stratification of thyroid nodules: A systematic review and meta-analysis","volume":"13","author":"Hu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.899575","article-title":"Validating and comparing C-TIRADS, K-TIRADS and ACR-TIRADS in stratifying the malignancy risk of thyroid nodules","volume":"13","author":"Chen","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-021-08450-3","article-title":"Performance of current ultrasound-based malignancy risk stratification systems for thyroid nodules in patients with follicular neoplasms","volume":"32","author":"Lin","year":"2022","journal-title":"Eur Radiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.s416403","article-title":"Comparing diagnostic efficacy of C-TIRADS positive features on different sizes of thyroid nodules","volume":"16","author":"Zhou","year":"2023","journal-title":"Int J Gen Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22015","article-title":"Use of the thyroid imaging, reporting, and data system (TI-RADS) scoring system for the evaluation of subcentimeter thyroid nodules","volume":"126","author":"Weiss","year":"2018","journal-title":"Cancer Cytopathol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-011-1813-1","article-title":"The diagnostic values of ultrasound and ultrasound-guided fine needle aspiration in subcentimeter-sized thyroid nodules","volume":"19","author":"Moon","year":"2012","journal-title":"Ann Surg Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.12014","article-title":"Taller-than-wide thyroid nodules with microcalcifications are at high risk of malignancy","volume":"34","author":"Papapostolou","year":"2020","journal-title":"In Vivo"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0372","article-title":"A taller-than-wide shape in thyroid nodules in transverse and longitudinal ultrasonographic planes and the prediction of malignancy","volume":"21","author":"Moon","year":"2011","journal-title":"Thyroid"},{"key":"B27","doi-asserted-by":"publisher","first-page":"717","DOI":"10.3390\/cancers14030717","article-title":"Risk stratification of thyroid nodules: From ultrasound features to TIRADS","volume":"14","author":"Rago","year":"2022","journal-title":"Cancers"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2012.05.019","article-title":"Ultrasound findings of papillary thyroid microcarcinoma: A review of 113 consecutive cases with histopathologic correlation","volume":"38","author":"Wang","year":"2012","journal-title":"Ultrasound Med Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2473070944","article-title":"Benign and malignant thyroid nodules: US differentiation--multicenter retrospective study","volume":"247","author":"Moon","year":"2008","journal-title":"Radiology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0096(199603)24:3<129::aid-jcu4>3.0.co;2-j","article-title":"Clinical significance of the comet-tail artifact in thyroid ultrasound","volume":"24","author":"Ahuja","year":"1996","journal-title":"J Clin Ultrasound"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191505","article-title":"Echogenic foci with comet-tail artifact in resected thyroid nodules: Not an absolute predictor of benign disease","volume":"13","author":"Wu","year":"2018","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2019181723","article-title":"Diagnostic performance of practice guidelines for thyroid nodules: Thyroid nodule size versus biopsy rates","volume":"291","author":"Ha","year":"2019","journal-title":"Radiology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1844286\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:46:12Z","timestamp":1791348372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1844286\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":32,"alternative-id":["10.3389\/fendo.2026.1844286"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1844286","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1844286"}}