{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:58:37Z","timestamp":1785549517364,"version":"3.56.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"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>Graves\u2019 disease (GD) and autoimmune thyroiditis (AIT) are two major causes of thyrotoxicosis that require correct diagnosis to plan appropriate treatment. The objectives of this study were to evaluate the usefulness of thyroid-related parameters for distinguishing GD from AIT and identify a novel index for differential diagnosis of thyrotoxicosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This retrospective study was performed using electronic medical records in Peking University People\u2019s Hospital (Beijing, China).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 650 patients with GD and 155 patients with AIT from December 2015 to October 2019 were included in cohort 1. Furthermore, 133 patients with GD and 14 patients with AIT from December 2019 to August 2020 were included in cohort 2 for validation of the novel index identified in cohort 1. All patients were of Chinese ethnicity and were newly diagnosed with either GD or AIT. Thyroid-related clinical information was collected before intervention by reviewing the patients\u2019 electronic medical records. Receiver operating characteristic curve analysis was used to identify the optimal cutoff for distinguishing GD from AIT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In cohort 1, thyroid-stimulating hormone (TSH) receptor antibody was identified as the best indicator for distinguishing GD from AIT. The area under the receiver operating characteristic curve was 0.99(95% confidence interval: 0.98\u20130.99, p&amp;lt;0.0001)and the optimal cutoff was 0.84 IU\/l (98% sensitivity and 99% specificity). The free triiodothyronine (FT3)\/TSH ratio (FT3\/TSH) was the second \u2013best for distinguishing GD from AIT, the area under the receiver operating characteristic curve of FT3\/TSH was 0.86 (95% confidence interval: 0.84\u20130.88, p&amp;lt;0.0001); its optimal cutoff was 1.99 pmol\/mIU (79% sensitivity and 80% specificity). Its effectiveness was confirmed in cohort 2 (81% sensitivity and 100% specificity).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The FT3\/TSH ratio is a new useful index for differential diagnosis of thyrotoxicosis, especially when combined with TRAb.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2020.620407","type":"journal-article","created":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T09:40:18Z","timestamp":1610185218000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Serum Ratio of Free Triiodothyronine to Thyroid-Stimulating Hormone: A Novel Index for Distinguishing Graves\u2019 Disease From Autoimmune Thyroiditis"],"prefix":"10.3389","volume":"11","author":[{"given":"Zhiyong","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Ren","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":"1965","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12060","article-title":"Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003-2005","volume":"78","author":"Nystr\u00f6m","year":"2013","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(90)90178-G","article-title":"Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter","volume":"89","author":"Berghout","year":"1990","journal-title":"Am J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.02.001","article-title":"Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism","volume":"322","author":"Gozu","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021799","article-title":"Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study","volume":"88","author":"Fatourechi","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3109\/00365513.2013.769623","article-title":"Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies","volume":"73","author":"Schwartz","year":"2013","journal-title":"Scand J Lab Invest"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.140.4.478","article-title":"Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (silent thyroiditis)","volume":"140","author":"Nikolai","year":"1980","journal-title":"Arch Intern Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s40618-014-0097-2","article-title":"Extrathyroidal manifestations of Graves\u2019 disease: a 2014 update","volume":"37","author":"Bartalena","year":"2014","journal-title":"J Endocrinol Invest"},{"key":"B8","first-page":"e1","article-title":"TSI assay utilization: impact on costs of Graves\u2019 hyperthyroidism diagnosis","volume":"18","author":"McKee","year":"2012","journal-title":"Am J Manag Care"},{"key":"B9","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":"Greenlee","year":"2016","journal-title":"Thyroid"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)92943-4","article-title":"Differentiation of thyrotoxicosis induced by thyroid destruction from Graves\u2019 disease","volume":"2","author":"Amino","year":"1978","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0533","article-title":"Determinants of serum T4 and T3 at the time of diagnosis in nosological types of thyrotoxicosis: a population-based study","volume":"169","author":"Carl\u00e9","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-65-2-359","article-title":"Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves\u2019 disease despite similar serum total T4 levels","volume":"65","author":"Shigemasa","year":"1987","journal-title":"J Clin Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-53-1-113","article-title":"Serum ratio of triiodothyronine to thyroxine, and thyroxine-binding globulin and calcitonin concentrations in Graves\u2019 disease and destruction-induced thyrotoxicosis","volume":"53","author":"Amino","year":"1981","journal-title":"J Clin Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1159\/000375445","article-title":"Bioassays for TSH receptor antibodies: an update","volume":"4","author":"Kahaly","year":"2015","journal-title":"Eur Thyroid J"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2012.07.003","article-title":"TSH receptor autoantibody immunoassay in patients with Graves\u2019 disease: improvement of diagnostic accuracy over different generations of methods","volume":"12","author":"Tozzoli","year":"2012","journal-title":"System Rev Meta Anal Autoimmun Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.amsu.2016.07.024","article-title":"Differentiating Graves\u2019 disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine","volume":"10","author":"Chutintorn","year":"2016","journal-title":"Ann Med Surg (Lond)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4836736","article-title":"Diagnostic values of free triiodothyronine and free thyroxine and the ratio of free triiodothyronine to free thyroxine in thyrotoxicosis","volume":"2018","author":"Chen","year":"2018","journal-title":"Int J Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.52.537","article-title":"Ratio of serum free triiodothyronine to free thyroxine in Graves\u2019 hyperthyroidism and thyrotoxicosis caused by painless thyroiditis","volume":"52","author":"Noh","year":"2005","journal-title":"Endocr J"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.01558.x","article-title":"Simple and practical parameters for differentiation between destruction-induced thyrotoxicosis and Graves\u2019 thyrotoxicosis","volume":"57","author":"Izumi","year":"2002","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/1050725042451248","article-title":"A new assay for thyrotropin receptor autoantibodies","volume":"14","author":"Smith","year":"2004","journal-title":"Thyroid"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1077051","article-title":"Comparison of M22-based ELISA and human-TSH-receptor-based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases","volume":"40","author":"Liu","year":"2008","journal-title":"Horm Metab Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.115162","article-title":"Intermethod variability in TSH-receptor antibody measurement: implication for the diagnosis of Graves\u2019 disease and for the follow-up of Graves ophthalmopathy","volume":"55","author":"Massart","year":"2009","journal-title":"Clin Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0119","article-title":"Evaluation of a new rapid and fully automated electrochemiluminescence immunoassay for thyrotropin Receptor autoantibodies","volume":"18","author":"Noh","year":"2008","journal-title":"Thyroid"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03512.x","article-title":"Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves\u2019 disease (GD): an international multicentre trial","volume":"71","author":"Schott","year":"2009","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1258\/acb.2011.011013","article-title":"Clinical performance of the Roche cobas e411 automated assay system for thyrotropin-receptor antibodies for the diagnosis of Graves\u2019 disease","volume":"48","author":"Syme","year":"2011","journal-title":"Ann Clin Biochem"},{"key":"B26","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s13317-010-0014-4","article-title":"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","volume":"1","author":"Tozzoli","year":"2010","journal-title":"Auto Immun Highlights"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2008.11.025","article-title":"Technical evaluation of the first fully automated assay for the detection of TSH receptor autoantibodies","volume":"401","author":"Hermsen","year":"2009","journal-title":"Clin Chim Acta"},{"key":"B28","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1507\/endocrj.52.29","article-title":"Rapid differential diagnosis of Graves\u2019 disease and painless thyroiditis using total T3\/T4 ratio, TSH, and total alkaline phosphatase activity","volume":"52","author":"Yanagisawa","year":"2005","journal-title":"Endocr J"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1999.00632.x","article-title":"Comparison of serum thyrotrophin concentrations determined by a third generation assay in patients with various types of overt and subclinical thyrotoxicosis","volume":"50","author":"Kasagi","year":"1999","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0178","article-title":"Sources of circulating 3,5,3\u2019-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases","volume":"92","author":"Laurberg","year":"2007","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.emc.2013.12.001","article-title":"Hyperthyroidism and Thyrotoxicosis","volume":"32","author":"Devereaux","year":"2014","journal-title":"Emerg Med Clin N Am"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0067","article-title":"Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China","volume":"30","author":"Yongze","year":"2020","journal-title":"Thyroid"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2020.620407\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T20:42:53Z","timestamp":1610570573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2020.620407\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":32,"alternative-id":["10.3389\/fendo.2020.620407"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2020.620407","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739427519.793582650","asserted-by":"object"}]},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"article-number":"620407"}}