{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:53:20Z","timestamp":1791608000987,"version":"4.3.4"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The rapid and accurate detection of thyroid-stimulating hormone (TSH) receptor antibodies has always been an urgent need for the clinical diagnosis and management of Graves\u2019 disease (GD). We aimed to\u00a0evaluate the use of an automated thyroid-stimulating immunoglobulin (TSI) bridge immunoassay in the diagnosis of GD and to analyze the relationship between TSI and the degree of hyperthyroidism.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 227 new-onset GD patients, 29 Hashimoto thyroiditis, 43 non-autoimmune thyroid diseases and 37 euthyroid controls were consecutively recruited. All participants accepted the measurement of their serum thyroid function and thyroid-associated antibodies, including TSI being measured by an Immulite 2000 bridge immunoassay and TSH receptor autoantibodies (TRAb) being measured by a third-generation Roche electrochemiluminescence immunoassay. The quantitative consistency between the TSI and TRAb detection methods was analyzed by using Passing-Bablok regression and Bland\u2013Altman plots. The diagnostic performance for GD was assessed by receiver operating characteristic (ROC) curve analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Among 227 GD patients (174 females and 53 males, with a mean age of 39\u00a0years), the quantitative TSI was positively correlated with TRAb (<jats:italic>r<\/jats:italic>\u2009=\u20090.8099). According to the cut-off values proposed by the manufacturers (TSI: 0.55\u00a0IU\/L, TRAb: 1.75\u00a0IU\/L), the positive rates of TSI and TRAb in new-onset GD patients were 96.92% and 95.15%, respectively. Both TSI and TRAb levels positively correlated with FT<jats:sub>4<\/jats:sub> levels (TSI: <jats:italic>r<\/jats:italic>\u2009=\u20090.243, TRAb: <jats:italic>r<\/jats:italic>\u2009=\u20090.317; all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and FT<jats:sub>3<\/jats:sub> levels (TSI: <jats:italic>r<\/jats:italic>\u2009=\u20090.288, TRAb: <jats:italic>r<\/jats:italic>\u2009=\u20090.360; all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) in new-onset GD patients. The ROC analysis showed that the optimal TSI cut-off value was 0.577\u00a0IU\/L for GD diagnosis in this Chinese population, with a sensitivity of 96.92% and a specificity of 97.25%, respectively. The optimal TRAb cut-off value of was 1.38\u00a0IU\/L, with a sensitivity of 96.92% and a specificity of 99.08%. There were no significant differences between the cut-off values obtained through the ROC analysis and those provided by the manufacturer for both TSI and TRAb when calculating their sensitivity and specificity in diagnosing GD. Among the 8 newly diagnosed GD cases with discordant qualitative antibody results, TSI was more likely than TRAb to match the clinical diagnosis of GD (6 TSI-positive vs. 2 TRAb-positive patients).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The automated TSI bridge immunoassay was positively correlated with thyroxine levels in new-onset GD patients and was more likely to be consistent with the clinical diagnosis of GD than with that of TRAb. The positive Immulite 2000 TSI cut-off value of 0.577\u00a0IU\/L for GD diagnosis in the Chinese population were close to the value recommended by the manufacturer.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-022-01114-3","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T10:04:27Z","timestamp":1661940267000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical evaluation of an automated TSI bridge immunoassay in the diagnosis of Graves\u2019 disease and its relationship to the degree of hyperthyroidism"],"prefix":"10.1186","volume":"22","author":[{"given":"Tianqi","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghai","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linong","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"issue":"16","key":"1114_CR1","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1510030","volume":"375","author":"TJ Smith","year":"2016","unstructured":"Smith TJ, Heged\u00fcs L. Graves\u2019 Disease. N Engl J Med. 2016;375(16):1552\u201365.","journal-title":"N Engl J Med"},{"issue":"3","key":"1114_CR2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1089\/thy.2016.0457","volume":"27","author":"EK Alexander","year":"2017","unstructured":"Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27(3):315\u201389.","journal-title":"Thyroid"},{"key":"1114_CR3","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1146\/annurev-pathol-012513-104713","volume":"9","author":"Y Tomer","year":"2014","unstructured":"Tomer Y. Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev Pathol. 2014;9:147\u201356.","journal-title":"Annu Rev Pathol"},{"issue":"2","key":"1114_CR4","first-page":"930","volume":"86","author":"TH Brix","year":"2001","unstructured":"Brix TH, Kyvik KO, Christensen K, Heged\u00fcs L. Evidence for a major role of heredity in Graves\u2019 disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab. 2001;86(2):930\u20134.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4S Suppl 1","key":"1114_CR5","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1097\/IOP.0000000000001052","volume":"34","author":"A Kotwal","year":"2018","unstructured":"Kotwal A, Stan M. Thyrotropin Receptor Antibodies-An Overview. Ophthalmic Plast Reconstr Surg. 2018;34(4S Suppl 1):S20-s7.","journal-title":"Ophthalmic Plast Reconstr Surg"},{"issue":"11","key":"1114_CR6","doi-asserted-by":"publisher","first-page":"4123","DOI":"10.1210\/jc.2012-2268","volume":"97","author":"F Brandt","year":"2012","unstructured":"Brandt F, Almind D, Christensen K, Green A, Brix TH, Heged\u00fcs L. Excess mortality in hyperthyroidism: the influence of preexisting comorbidity and genetic confounding: a danish nationwide register-based cohort study of twins and singletons. J Clin Endocrinol Metab. 2012;97(11):4123\u20139.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1114_CR7","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1159\/000490384","volume":"7","author":"GJ Kahaly","year":"2018","unstructured":"Kahaly GJ, Bartalena L, Heged\u00fcs L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association Guideline for the Management of Graves\u2019 Hyperthyroidism. European thyroid journal. 2018;7(4):167\u201386.","journal-title":"European thyroid journal"},{"issue":"10","key":"1114_CR8","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1089\/thy.2016.0229","volume":"26","author":"DS Ross","year":"2016","unstructured":"Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343\u2013421.","journal-title":"Thyroid"},{"issue":"2","key":"1114_CR9","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.autrev.2012.07.003","volume":"12","author":"R Tozzoli","year":"2012","unstructured":"Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves\u2019 disease: improvement of diagnostic accuracy over different generations of methods Systematic review and meta-analysis. Autoimmun Rev. 2012;12(2):107\u201313.","journal-title":"Autoimmun Rev"},{"issue":"1","key":"1114_CR10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1159\/000375445","volume":"4","author":"GJ Kahaly","year":"2015","unstructured":"Kahaly GJ. Bioassays for TSH Receptor Antibodies: Quo Vadis? European Thyroid J. 2015;4(1):3\u20135.","journal-title":"European Thyroid J"},{"issue":"6","key":"1114_CR11","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1210\/jc.2012-4309","volume":"98","author":"G Barbesino","year":"2013","unstructured":"Barbesino G, Tomer Y. Clinical review: Clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab. 2013;98(6):2247\u201355.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1114_CR12","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1210\/jcem-52-6-1204","volume":"52","author":"WE Hinds","year":"1981","unstructured":"Hinds WE, Takai N, Rapoport B, Filetti S, Clark OH. Thyroid-stimulating immunoglobulin bioassay using cultured human thyroid cells. J Clin Endocrinol Metab. 1981;52(6):1204\u201310.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"1114_CR13","first-page":"499","volume":"76","author":"P Vitti","year":"1993","unstructured":"Vitti P, Elisei R, Tonacchera M, Chiovato L, Mancusi F, Rago T, et al. Detection of thyroid-stimulating antibody using Chinese hamster ovary cells transfected with cloned human thyrotropin receptor. J Clin Endocrinol Metab. 1993;76(2):499\u2013503.","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"1114_CR14","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1046\/j.1365-2265.1998.00619.x","volume":"49","author":"PF Watson","year":"1998","unstructured":"Watson PF, Ajjan RA, Phipps J, Metcalfe R, Weetman AP. A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves\u2019 disease. Clin Endocrinol. 1998;49(5):577\u201381.","journal-title":"Clin Endocrinol"},{"issue":"1","key":"1114_CR15","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1515\/cclm-2016-0197","volume":"55","author":"R Tozzoli","year":"2017","unstructured":"Tozzoli R, D\u2019Aurizio F, Villalta D, Giovanella L. Evaluation of the first fully automated immunoassay method for the measurement of stimulating TSH receptor autoantibodies in Graves\u2019 disease. Clin Chem Lab Med. 2017;55(1):58\u201364.","journal-title":"Clin Chem Lab Med"},{"issue":"1","key":"1114_CR16","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1177\/0004563217700655","volume":"55","author":"C Autilio","year":"2018","unstructured":"Autilio C, Morelli R, Locantore P, Pontecorvi A, Zuppi C, Carrozza C. Stimulating TSH receptor autoantibodies immunoassay: analytical evaluation and clinical performance in Graves\u2019 disease. Ann Clin Biochem. 2018;55(1):172\u20137.","journal-title":"Ann Clin Biochem"},{"issue":"12","key":"1114_CR17","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1055\/s-0035-1554662","volume":"47","author":"CU Frank","year":"2015","unstructured":"Frank CU, Braeth S, Dietrich JW, Wanjura D, Loos U. Bridge Technology with TSH Receptor Chimera for Sensitive Direct Detection of TSH Receptor Antibodies Causing Graves\u2019 Disease: Analytical and Clinical Evaluation. Horm Metab Res. 2015;47(12):880\u20138.","journal-title":"Horm Metab Res"},{"issue":"1","key":"1114_CR18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s12020-020-02386-2","volume":"71","author":"X Cheng","year":"2021","unstructured":"Cheng X, Chai X, Ma C, Jia Q, Zhao H, Dong Z, et al. Clinical diagnostic performance of a fully automated TSI immunoassay vs that of an automated anti-TSHR immunoassay for Graves\u2019 disease: a Chinese multicenter study. Endocrine. 2021;71(1):139\u201348.","journal-title":"Endocrine"},{"issue":"1","key":"1114_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s13317-018-0102-4","volume":"9","author":"D Villalta","year":"2018","unstructured":"Villalta D, D\u2019Aurizio F, Da Re M, Ricci D, Latrofa F, Tozzoli R. Diagnostic accuracy of a new fluoroenzyme immunoassay for the detection of TSH receptor autoantibodies in Graves\u2019 disease. Auto- Immun Highlights. 2018;9(1):3.","journal-title":"Auto- Immun Highlights"},{"issue":"10","key":"1114_CR20","first-page":"876","volume":"46","author":"Chinese Medical Association Endocrinology Society Group","year":"2007","unstructured":"Chinese Medical Association Endocrinology Society Group. Chinese thyroid disease diagnosis and treatment guidelines. Chin J Intern Med. 2007;46(10):876\u201382.","journal-title":"Chin J Intern Med"},{"key":"1114_CR21","volume-title":"Diagnostics","author":"XH Wan","year":"2013","unstructured":"Wan XH. Diagnostics. China, Beijing: People\u2019s Medical Publishing House; 2013."},{"issue":"1","key":"1114_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/thy.2015.0020","volume":"26","author":"BR Haugen","year":"2016","unstructured":"Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 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. Thyroid. 2016;26(1):1\u2013133.","journal-title":"Thyroid"},{"issue":"6","key":"1114_CR23","doi-asserted-by":"publisher","first-page":"988","DOI":"10.4158\/EP12280.GL","volume":"18","author":"JR Garber","year":"2012","unstructured":"Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988\u20131028.","journal-title":"Endocr Pract"},{"issue":"12","key":"1114_CR24","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1055\/s-0042-121012","volume":"48","author":"S Allelein","year":"2016","unstructured":"Allelein S, Ehlers M, Goretzki S, Hermsen D, Feldkamp J, Haase M, et al. Clinical Evaluation of the First Automated Assay for the Detection of Stimulating TSH Receptor Autoantibodies. Horm Metab Res. 2016;48(12):795\u2013801.","journal-title":"Horm Metab Res"},{"issue":"2","key":"1114_CR25","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/cen.14130","volume":"92","author":"L Scappaticcio","year":"2020","unstructured":"Scappaticcio L, Trimboli P, Keller F, Imperiali M, Piccardo A, Giovanella L. Diagnostic testing for Graves\u2019 or non-Graves\u2019 hyperthyroidism: A comparison of two thyrotropin receptor antibody immunoassays with thyroid scintigraphy and ultrasonography. Clin Endocrinol. 2020;92(2):169\u201378.","journal-title":"Clin Endocrinol"},{"issue":"6","key":"1114_CR26","doi-asserted-by":"publisher","first-page":"615","DOI":"10.4158\/EP.13.6.615","volume":"13","author":"UM Kabadi","year":"2007","unstructured":"Kabadi UM, Premachandra BN. Serum thyrotropin in Graves\u2019 disease: a more reliable index of circulating thyroid-stimulating immunoglobulin level than thyroid function? Endocr Pract. 2007;13(6):615\u20139.","journal-title":"Endocr Pract"},{"issue":"2","key":"1114_CR27","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s13317-010-0014-4","volume":"1","author":"R Tozzoli","year":"2010","unstructured":"Tozzoli R, Kodermaz G, Villalta D, Bagnasco M, Pesce G, Bizzaro N. Accuracy of receptor-based methods for detection of thyrotropin-receptor autoantibodies: a new automated third-generation immunoassay shows higher analytical and clinical sensitivity for the differential diagnosis of hyperthyroidism. Auto Immun Highlights. 2010;1(2):95\u2013100.","journal-title":"Auto Immun Highlights"}],"container-title":["BMC Endocrine Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-022-01114-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12902-022-01114-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-022-01114-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T10:05:15Z","timestamp":1661940315000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcendocrdisord.biomedcentral.com\/articles\/10.1186\/s12902-022-01114-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,31]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1114"],"URL":"https:\/\/doi.org\/10.1186\/s12902-022-01114-3","relation":{},"ISSN":["1472-6823"],"issn-type":[{"value":"1472-6823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,31]]},"assertion":[{"value":"30 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics\u00a0approval\u00a0was obtained from the Peking University People\u2019s Hospital Research Ethics\u00a0Committee (2021PHB001-001). Written informed consent was obtained from individual participants or their guardian. All experiments were performed in accordance with relevant guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author(s) declare no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"218"}}