{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:51:08Z","timestamp":1773276668808,"version":"3.50.1"},"reference-count":26,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:p>Differences in the epitopes of thyroid-stimulating antibodies (TSAbs) from patients with untreated Graves\u2019 disease were compared with long-term response to antithyroid drugs. Epitopes were measured using Chinese hamster ovary cells transfected with wild-type human TSH receptor (TSHR) and two receptor chimeras, wherein TSHR residues 9\u2013165 or 90\u2013165 had been substituted with comparable residues of the LH\/chorionic gonadotropin receptor. Of 159 patients studied, 52 (32.7%) exhibited positive TSAb activity with one or both chimera lines (heterogeneous group), and 107 (67.3%) had no activity with either (homogeneous group). Independent of all other parameters, patients with heterogeneous epitopes responded more favorably to oral antithyroid drugs than patients with homogeneous epitopes (65.4% vs. 41.9%, P = 0.011: estimated odds ratio by logistic regression, 2.17). Although most clinical parameters were not different at presentation, significant differences in the size of goiters, total T3 concentrations, and titers of TSH-binding inhibitory Igs were evident in the successfully treated group (n = 80) by comparison to the group of patients whose treatment failed (n = 79). Alone, these three parameters did not predict outcome; however, when either of these parameters were considered together with epitope heterogeneity, predictability of a positive therapeutic response was increased to nearly 80%. Thus, the presence of TSAbs with a heterogeneous epitope in a patient with Graves\u2019 disease is not only associated with a favorable response to antithyroid drug treatment, it may help predict the response to treatment when the patient is initially seen.<\/jats:p>","DOI":"10.1210\/jc.2002-020389","type":"journal-article","created":{"date-parts":[[2003,1,8]],"date-time":"2003-01-08T17:42:41Z","timestamp":1042047761000},"page":"117-124","source":"Crossref","is-referenced-by-count":24,"title":["Epitope Heterogeneity of Thyroid-Stimulating Antibodies Predicts Long-Term Outcome in Graves\u2019 Patients Treated with Antithyroid Drugs"],"prefix":"10.1210","volume":"88","author":[{"given":"Tae Yong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital (T.Y.K., Y.J.P., D.J.P., B.Y.C.), Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Joo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital (T.Y.K., Y.J.P., D.J.P., B.Y.C.), Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do Joon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital (T.Y.K., Y.J.P., D.J.P., B.Y.C.), Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Kyung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dankook University College of Medicine (H.C.), Cheonan 330-715, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Bae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine (W.B.K.), Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard D.","family":"Kohn","sequence":"additional","affiliation":[{"name":"Edison Biotechnology Institute and Ohio University College of Osteopathic Medicine (L.D.K.), Athens, Ohio 45701"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital (T.Y.K., Y.J.P., D.J.P., B.Y.C.), Seoul 110-744, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071616564306200_R1","first-page":"673","article-title":"The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies.","volume":"19","author":"Rapoport","year":"1998","journal-title":"Endocr Rev"},{"key":"2020071616564306200_R2","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.1210\/jcem.83.11.5056-1","article-title":"Thyroid controversy\u2014stimulating antibodies.","volume":"83","author":"Davies","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R3","first-page":"98","article-title":"Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves\u2019 disease.","volume":"78","author":"Feldt-Rasmussen","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0006-291X(91)91335-A","article-title":"Immunoglobulins from Graves\u2019 disease patients interact with different sites on TSH receptor\/LH-CG receptor chimeras than either TSH or immunoglobulins from idiopathic myxedema patients.","volume":"179","author":"Tahara","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071616564306200_R5","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1172\/JCI115297","article-title":"Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin\/chorionic gonadotropin receptors.","volume":"88","author":"Nagayama","year":"1991","journal-title":"J Clin Invest"},{"key":"2020071616564306200_R6","doi-asserted-by":"crossref","first-page":"10900","DOI":"10.1016\/S0021-9258(18)82070-1","article-title":"Structure-function studies of the human thyrotropin receptor. Inhibition of binding of labeled thyrotropin (TSH) by synthetic human TSH receptor peptides.","volume":"268","author":"Morris","year":"1993","journal-title":"J Biol Chem"},{"key":"2020071616564306200_R7","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1530\/eje.0.1330283","article-title":"Presence of heterogeneous thyroid-stimulating antibodies in sera from individual Graves\u2019 patients as shown by synthesized thyrotropin receptor peptide application: evidence showing two independent epitopes and a possible recognition of two epitopic regions by one antibody molecule.","volume":"133","author":"Sugawa","year":"1995","journal-title":"Eur J Endocrinol"},{"key":"2020071616564306200_R8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1530\/eje.0.1320062","article-title":"Thyroid-stimulating antibodies in sera from patients with Graves\u2019 disease are heterogeneous in epitope recognition.","volume":"132","author":"Ueda","year":"1995","journal-title":"Eur J Endocrinol"},{"key":"2020071616564306200_R9","first-page":"1758","article-title":"Epitopes for thyroid-stimulating antibodies in Graves\u2019 sera: a possible link of heterogeneity to differences in response to antithyroid drug treatment.","volume":"81","author":"Kim","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R10","first-page":"1953","article-title":"Changes in epitopes for thyroid-stimulating antibodies in Graves\u2019 disease sera during treatment of hyperthyroidism: therapeutic implications.","volume":"82","author":"Kim","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1089\/thy.1997.7.13","article-title":"Subtypes of anti-TSH receptor antibodies classified by various assays using CHO cells expressing wild-type or chimeric human TSH receptor.","volume":"7","author":"Watanabe","year":"1997","journal-title":"Thyroid"},{"key":"2020071616564306200_R12","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1089\/thy.2000.10.579","article-title":"The prevalence and clinical significance of blocking thyrotropin receptor antibodies in untreated hyperthyroid Graves\u2019 disease.","volume":"10","author":"Kim","year":"2000","journal-title":"Thyroid"},{"key":"2020071616564306200_R13","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/0002-9394(69)91246-X","article-title":"Classification of the eye changes of Graves\u2019 disease.","volume":"68","author":"Werner","year":"1969","journal-title":"Am J Ophthalmol"},{"key":"2020071616564306200_R14","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1365-2265.1992.tb02269.x","article-title":"Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody activities as prognostic markers for discontinuation of antithyroid drug treatment in patients with Graves\u2019 disease.","volume":"36","author":"Cho","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071616564306200_R15","first-page":"2986","article-title":"Graves\u2019 hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine\u2014a prospective, randomized study. Thyroid Study Group.","volume":"81","author":"Torring","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R16","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1365-2265.1995.tb02919.x","article-title":"A study of untreated Graves\u2019 patients with undetectable TSH binding inhibitor immunoglobulins and the effect of anti-thyroid drugs.","volume":"43","author":"Kawai","year":"1995","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071616564306200_R17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/thy.1998.8.119","article-title":"The prognostic value of thyrotropin receptor antibody measurement in the early stages of treatment of Graves\u2019 disease with antithyroid drugs.","volume":"8","author":"Michelangeli","year":"1998","journal-title":"Thyroid"},{"key":"2020071616564306200_R18","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1089\/thy.1997.7.369","article-title":"Clinical features of patients with Graves\u2019 disease undergoing remission after antithyroid drug treatment.","volume":"7","author":"Vitti","year":"1997","journal-title":"Thyroid"},{"key":"2020071616564306200_R19","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0889-8529(05)70135-3","article-title":"Anti-TSH receptor antibodies in clinical practice.","volume":"29","author":"Orgiazzi","year":"2000","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071616564306200_R20","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1089\/thy.1999.9.531","article-title":"Epitope heterogeneity of thyrotropin receptor-blocking antibodies in Graves\u2019 patients as detected with wild-type versus chimeric thyrotropin receptors.","volume":"9","author":"Grasso","year":"1999","journal-title":"Thyroid"},{"key":"2020071616564306200_R21","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1210\/jcem-43-3-543","article-title":"Dissociation of responsiveness to thyrotropin-releasing hormone and thyroid suppressibility following antithyroid drug therapy of hyperthyroidism.","volume":"43","author":"Martino","year":"1976","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R22","first-page":"1038","article-title":"Age and gender predict the outcome of treatment for Graves\u2019 hyperthyroidism.","volume":"85","author":"Allahabadia","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R23","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1210\/jcem-56-6-1202","article-title":"Heterogeneity of the Graves\u2019 immunoglobulins directed toward the thyrotropin receptor-adenylate cyclase system.","volume":"56","author":"Carayon","year":"1983","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616564306200_R24","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.1365-2265.1983.tb00602.x","article-title":"The assay of Graves\u2019 immunoglobulins: a comparison of different methods.","volume":"18","author":"Hardisty","year":"1983","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071616564306200_R25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-8981(99)00235-1","article-title":"Thyrotropin-receptor antibodies in thyroid diseases: advances in detection techniques and clinical applications.","volume":"293","author":"Gupta","year":"2000","journal-title":"Clin Chim Acta"},{"key":"2020071616564306200_R26","first-page":"3647","article-title":"Epitope mapping of TSH receptor-blocking antibodies in Graves\u2019 disease that appear during pregnancy.","volume":"86","author":"Kung","year":"2001","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/88\/1\/117\/10742533\/jcem0117.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/88\/1\/117\/10742533\/jcem0117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T04:30:19Z","timestamp":1622694619000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/88\/1\/117\/2846017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,1]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2002-020389","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1,1]]}}}