{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:46Z","timestamp":1792793866933,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010378","name":"Stichting Wetenschappelijk Onderzoek Oogziekenhuis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010378","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rotterdamse Stichting voor Blindenbelangen"},{"name":"Stichting Ooglijders"},{"DOI":"10.13039\/501100010321","name":"Oogfonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation Combined Ophthalmic Research Rotterdam","id":[{"id":"https:\/\/ror.org\/03cfd9m08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Graves\u2019 orbitopathy (GO) typically occurs in hyperthyroid patients with detectable thyroid-stimulating hormone (TSH) receptor antibodies (TSH-R-Ab). Rarely, it presents in euthyroid patients without detectable TSH-R-Ab, as determined by thyrotropin-binding inhibitory immunoglobulin (TBII) assays, posing a diagnostic challenge. While functional bioassays improve TSH-R-Ab detection in euthyroid GO (EGO), their complexity limits clinical use. A novel, highly sensitive bioassay (Turbo TSI) offers a faster and simplified protocol. In this study, we explore Turbo TSI in TBII-negative EGO and compare it to 2 distinct types of binding immunoassays. Furthermore, we describe a large cohort and compare clinical characteristics to hyperthyroid GO patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical features, thyroid function, and TBII levels of 20 cases were recorded retrospectively. If available, biobank serum was used to reassess TSH-R-Ab levels with Turbo TSI bioassay and bridge-based TSI binding immunoassay. TBII-negative EGO patients were compared to 40 hyperthyroid GO controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All cases were TBII-negative and euthyroid at presentation. From 6 patients, biobank serum was available. Two of these sera were found positive with bridge-based TSI binding immunoassay. In contrast, all 6 sera were found positive with the Turbo TSI bioassay. Compared to hyperthyroid GO, TBII-negative EGO patients presented unilaterally\/asymmetrically more often, had a milder and less active phenotype, and required less surgical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TSH-R-Ab are not absent in TBII-negative EGO, but require highly sensitive bioassays for detection. In contrast to traditional bioassays, Turbo TSI offers a simple and fast protocol and can therefore facilitate diagnosis in these patients. Euthyroid GO presents with a milder phenotype than hyperthyroid GO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf210","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:11:20Z","timestamp":1760011880000},"page":"575-584","source":"Crossref","is-referenced-by-count":6,"title":["Rapid and sensitive bioassay for thyroid-stimulating immunoglobulin detection in thyrotropin-binding inhibitory immunoglobulin\u2013negative euthyroid Graves\u2019 orbitopathy"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-0012","authenticated-orcid":false,"given":"Gijsbert J","family":"H\u00f6tte","sequence":"first","affiliation":[{"name":"Department of Oculoplastic, Orbital and Lacrimal Surgery, The Rotterdam Eye Hospital , Rotterdam, 3000 LM ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Van der Burg","sequence":"additional","affiliation":[{"name":"Department of Oculoplastic, Orbital and Lacrimal Surgery, The Rotterdam Eye Hospital , Rotterdam, 3000 LM ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem A","family":"Dik","sequence":"additional","affiliation":[{"name":"Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam , Rotterdam, 3000 CA ,","place":["The Netherlands"]},{"name":"Academic Center for Thyroid Diseases, Erasmus MC University Medical Center Rotterdam , Rotterdam, 3000 CA ,","place":["The Netherlands"]},{"name":"Laboratory Medical Immunology, Reinier Haga Medisch Diagnostisch Centrum (RHMDC) , Delft, 2600 GA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"De Bie","sequence":"additional","affiliation":[{"name":"Department of Oculoplastic, Orbital and Lacrimal Surgery, The Rotterdam Eye Hospital , 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Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Van der Weerd","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Franciscus Gasthuis & Vlietland , Rotterdam, 3045 PM ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Martin","family":"Van Hagen","sequence":"additional","affiliation":[{"name":"Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam , Rotterdam, 3000 CA ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine, Section Allergy and Clinical Immunology, Erasmus MC University Medical Center Rotterdam , Rotterdam, 3000 CA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion","family":"Paridaens","sequence":"additional","affiliation":[{"name":"Department of Oculoplastic, Orbital and Lacrimal Surgery, The Rotterdam Eye Hospital , Rotterdam, 3000 LM 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