{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:26:57Z","timestamp":1790954817557,"version":"4.1.0"},"reference-count":41,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Positive antithyroglobulin (TgAb) and\/or antithyroid peroxidase antibodies (TPOAb) at baseline indicate a high risk of thyroid immune-related adverse events (irAEs) induced by antiprogrammed cell death-1 antibodies (anti-PD-1-Ab). However, whether the positivity patterns of both antibodies are associated with the risk of thyroid irAEs is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of the present study was to clarify the association of the pattern of TgAb and TPOAb positivity at baseline with the risk of thyroid irAEs induced by anti-PD-1-Ab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients (n = 516) were evaluated for TgAb and TPOAb at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after initiating anti-PD-1-Ab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty-one (9.9%) patients developed thyroid irAEs (thyrotoxicosis in 34, hypothyroidism without prior thyrotoxicosis in 17). Twenty-five patients subsequently developed hypothyroidism following thyrotoxicosis. The cumulative incidence of thyroid irAEs differed among 4 groups classified by the presence of TgAb\/TPOAb at baseline (group 1: TgAb-(\u2212)\/TPOAb-(\u2212), 4.6% [19\/415]; group 2: TgAb-(\u2212)\/TPOAb-(+), 15.8% [9\/57]; group 3: TgAb-(+)\/TPOAb-(\u2212), 42.1% [8\/19]; group 4: TgAb-(+)\/TPOAb-(+), 60.0% [15\/25]) as follows: groups 1 vs 2-4 (P \u2264 .001) and groups 2 vs 3 (P = .008) and 4 (P &amp;lt; .001). There were different incidences of thyrotoxicosis (groups 1-4, 3.1%, 5.3%, 31.6%, 48.0%, respectively; P &amp;lt; .001) in groups 1 vs 3 and 4, and groups 2 vs 3 and 4, and of hypothyroidism (groups 1-4: 2.9%, 15.8%, 31.6%, 60.0%, respectively; P &amp;lt; .001) in groups 1 vs 2 to 4, and groups 2 vs 4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The risk of thyroid irAEs was affected by the pattern of TgAb and TPOAb positivity at baseline; there were high risks of thyrotoxicosis in patients with TgAb-(+) and of hypothyroidism in patients with TgAb-(+) and those with TPOAb-(+).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgad231","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T17:02:09Z","timestamp":1682096529000},"page":"e1056-e1062","source":"Crossref","is-referenced-by-count":37,"title":["Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2037-0095","authenticated-orcid":false,"given":"Xin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya 466-8550 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-0337","authenticated-orcid":false,"given":"Shintaro","family":"Iwama","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya 466-8550 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya 466-8550 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Ando","sequence":"additional","affiliation":[{"name":"Center for Advanced Medicine and Clinical Research, Nagoya University Hospital , Showa-ku, Nagoya 466-8550 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-1997","authenticated-orcid":false,"given":"Hiroshi","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine , Showa-ku, Nagoya 466-8550 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"issue":"4","key":"2023091800455987100_dgad231-B1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"2023091800455987100_dgad231-B2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"issue":"26","key":"2023091800455987100_dgad231-B3","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"issue":"19","key":"2023091800455987100_dgad231-B4","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"issue":"17","key":"2023091800455987100_dgad231-B5","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N Engl J Med"},{"issue":"6","key":"2023091800455987100_dgad231-B6","doi-asserted-by":"crossref","first-page":"e002435","DOI":"10.1136\/jitc-2021-002435","article-title":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","volume":"9","author":"Brahmer","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"1","key":"2023091800455987100_dgad231-B7","doi-asserted-by":"crossref","first-page":"101370","DOI":"10.1016\/j.beem.2019.101370","article-title":"New insight in endocrine-related adverse events associated to immune checkpoint blockade","volume":"34","author":"Elia","year":"2020","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"10","key":"2023091800455987100_dgad231-B8","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.3390\/ijms20102560","article-title":"Autoimmune endocrine dysfunctions associated with cancer immunotherapies","volume":"20","author":"Ferrari","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"2","key":"2023091800455987100_dgad231-B9","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3803\/EnM.2021.1007","article-title":"Clinical characteristics, management, and potential biomarkers of endocrine dysfunction induced by immune checkpoint inhibitors","volume":"36","author":"Iwama","year":"2021","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"10","key":"2023091800455987100_dgad231-B10","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1089\/thy.2020.0032","article-title":"Thyroid toxicity following immune checkpoint inhibitor treatment in advanced cancer","volume":"30","author":"Muir","year":"2020","journal-title":"Thyroid"},{"issue":"3","key":"2023091800455987100_dgad231-B11","doi-asserted-by":"crossref","first-page":"101660","DOI":"10.1016\/j.beem.2022.101660","article-title":"Immune checkpoint inhibitor-related thyroid dysfunction","volume":"36","author":"Iwama","year":"2022","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"7","key":"2023091800455987100_dgad231-B12","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1507\/endocrj.EJ19-0163","article-title":"Management of immune-related adverse events in endocrine organs induced by immune checkpoint inhibitors: clinical guidelines of the Japan Endocrine Society","volume":"66","author":"Arima","year":"2019","journal-title":"Endocr J"},{"issue":"3","key":"2023091800455987100_dgad231-B13","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/annonc\/mdw640","article-title":"Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer","volume":"28","author":"Osorio","year":"2017","journal-title":"Ann Oncol"},{"issue":"11","key":"2023091800455987100_dgad231-B14","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1210\/jc.2016-2300","article-title":"Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab","volume":"101","author":"de Filette","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2023091800455987100_dgad231-B15","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1210\/jc.2017-00448","article-title":"Pembrolizumab-induced thyroiditis: comprehensive clinical review and insights into underlying involved mechanisms","volume":"102","author":"Delivanis","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2023091800455987100_dgad231-B16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/js.2017-00432","article-title":"Patients with antithyroid antibodies are prone to develop destructive thyroiditis by nivolumab: a prospective study","volume":"2","author":"Kobayashi","year":"2018","journal-title":"J Endocr Soc"},{"issue":"6","key":"2023091800455987100_dgad231-B17","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/s41416-020-0736-7","article-title":"Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study","volume":"122","author":"Okada","year":"2020","journal-title":"Br J Cancer"},{"issue":"4","key":"2023091800455987100_dgad231-B18","doi-asserted-by":"crossref","first-page":"e1620","DOI":"10.1210\/clinem\/dgab829","article-title":"Increased risk of thyroid dysfunction by PD-1 and CTLA-4 blockade in patients without thyroid autoantibodies at baseline","volume":"107","author":"Iwama","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2023091800455987100_dgad231-B19","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.autrev.2014.01.007","article-title":"Hashimoto thyroiditis: clinical and diagnostic criteria","volume":"13","author":"Caturegli","year":"2014","journal-title":"Autoimmun Rev"},{"key":"2023091800455987100_dgad231-B20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jtbi.2014.12.015","article-title":"Thyroid autoimmunity as a window to autoimmunity: an explanation for sex differences in the prevalence of thyroid autoimmunity","volume":"375","author":"Merrill","year":"2015","journal-title":"J Theor Biol"},{"issue":"10","key":"2023091800455987100_dgad231-B21","doi-asserted-by":"crossref","first-page":"e4115","DOI":"10.1210\/clinem\/dgac467","article-title":"Elevated TSH level, TgAb, and prior use of ramucirumab or TKIs as risk factors for thyroid dysfunction in PD-L1 blockade","volume":"107","author":"Kobayashi","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"230","key":"2023091800455987100_dgad231-B22","doi-asserted-by":"crossref","first-page":"230ra45","DOI":"10.1126\/scitranslmed.3008002","article-title":"Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody","volume":"6","author":"Iwama","year":"2014","journal-title":"Sci Transl Med"},{"issue":"5","key":"2023091800455987100_dgad231-B23","doi-asserted-by":"crossref","first-page":"e002493","DOI":"10.1136\/jitc-2021-002493","article-title":"Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors","volume":"9","author":"Kobayashi","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"8","key":"2023091800455987100_dgad231-B24","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2337\/dbi18-0002","article-title":"Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors","volume":"67","author":"Stamatouli","year":"2018","journal-title":"Diabetes"},{"key":"2023091800455987100_dgad231-B25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jaut.2019.03.005","article-title":"Inflammatory myopathy associated with PD-1 inhibitors","volume":"100","author":"Seki","year":"2019","journal-title":"J Autoimmun"},{"issue":"11","key":"2023091800455987100_dgad231-B26","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1111\/cas.13800","article-title":"Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab","volume":"109","author":"Kimbara","year":"2018","journal-title":"Cancer Sci"},{"key":"2023091800455987100_dgad231-B27","doi-asserted-by":"crossref","first-page":"886930","DOI":"10.3389\/fendo.2022.886930","article-title":"Immune related adverse events of the thyroid\u2014a narrative review","volume":"13","author":"Muir","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"12","key":"2023091800455987100_dgad231-B28","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/thy.2018.0418","article-title":"Histology of nivolumab-induced thyroiditis","volume":"28","author":"Neppl","year":"2018","journal-title":"Thyroid"},{"issue":"2","key":"2023091800455987100_dgad231-B29","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/jcu.1870140208","article-title":"Sonography of Hashimoto\u2019s thyroiditis","volume":"14","author":"Hayashi","year":"1986","journal-title":"J Clin Ultrasound"},{"issue":"5","key":"2023091800455987100_dgad231-B30","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1507\/endocrj1954.32.681","article-title":"Echographic findings and histological feature of the thyroid: a reverse relationship between the level of echo-amplitude and lymphocytic infiltration","volume":"32","author":"Yoshida","year":"1985","journal-title":"Endocrinol Jpn"},{"issue":"593","key":"2023091800455987100_dgad231-B31","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abb7495","article-title":"CD4+ T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice","volume":"13","author":"Yasuda","year":"2021","journal-title":"Sci Transl Med"},{"key":"2023091800455987100_dgad231-B32","first-page":"133","article-title":"Cellular and antibody mediated cytotoxicity in autoimmune thyroid disease","volume":"281","author":"Bogner","year":"1987","journal-title":"Acta Endocrinol Suppl"},{"issue":"1","key":"2023091800455987100_dgad231-B33","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1530\/eje.0.1320069","article-title":"Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis","volume":"132","author":"Bogner","year":"1995","journal-title":"Eur J Endocrinol"},{"issue":"3","key":"2023091800455987100_dgad231-B34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1297\/cpe.2022-0002","article-title":"Higher serum thyroid autoantibody value is a risk factor of hypothyroidism in children and young adults with chronic thyroiditis","volume":"31","author":"Shimura","year":"2022","journal-title":"Clin Pediatr Endocrinol"},{"issue":"1","key":"2023091800455987100_dgad231-B35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2265.1995.tb01894.x","article-title":"The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey","volume":"43","author":"Vanderpump","year":"1995","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"7","key":"2023091800455987100_dgad231-B36","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1210\/jcem.87.7.8678","article-title":"Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies","volume":"87","author":"Huber","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"17","key":"2023091800455987100_dgad231-B37","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"issue":"7","key":"2023091800455987100_dgad231-B38","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EC-18-0068","article-title":"Society for Endocrinology endocrine emergency guidance: acute management of the endocrine complications of checkpoint inhibitor therapy","volume":"7","author":"Higham","year":"2018","journal-title":"Endocr Connect"},{"issue":"1","key":"2023091800455987100_dgad231-B39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s40425-017-0300-z","article-title":"Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group","volume":"5","author":"Puzanov","year":"2017","journal-title":"J Immunother Cancer"},{"issue":"3","key":"2023091800455987100_dgad231-B40","doi-asserted-by":"crossref","first-page":"230","DOI":"10.6004\/jnccn.2020.0012","article-title":"NCCN guidelines insights: management of immunotherapy-related toxicities, version 1.2020","volume":"18","author":"Thompson","year":"2020","journal-title":"J Natl Compr Canc Netw"},{"issue":"2","key":"2023091800455987100_dgad231-B41","first-page":"2140","article-title":"Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade","volume":"18","author":"Sakakida","year":"2019","journal-title":"Oncol Lett"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgad231\/50204091\/dgad231.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/10\/e1056\/51533525\/dgad231.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/10\/e1056\/51533525\/dgad231.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T20:46:45Z","timestamp":1694983605000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/10\/e1056\/7135935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,4,21]]},"published-print":{"date-parts":[[2023,9,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgad231","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,10]]},"published":{"date-parts":[[2023,4,21]]}}}