{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:30:06Z","timestamp":1789864206881,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T00:00:00Z","timestamp":1485475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"Summary<\/jats:title>\n \n Context<\/jats:title>\n Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course.<\/jats:p>\n <\/jats:sec>\n \n Design and patients<\/jats:title>\n Consecutive patients with melanoma treated with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab were identified. Baseline thyroid function tests were used to exclude those with pre\u2010existing thyroid abnormalities, and thyroid function tests during treatment used to identify those with thyroid dysfunction.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Rates of overt thyroid dysfunction were in keeping with the published phase 3 trials. Hypothyroidism occurred in 13\u00b70% treated with a programmed death receptor\u20101 (\n PD<\/jats:styled-content>\n \u20101) inhibitor and 22\u00b72% with a combination of\n PD<\/jats:styled-content>\n \u20101 inhibitor and ipilimumab. Transient subclinical hyperthyroidism was observed in 13\u00b70% treated with a\n PD<\/jats:styled-content>\n \u20101 inhibitor, 15\u00b79% following a\n PD<\/jats:styled-content>\n \u20101 inhibitor, and 22\u00b72% following combination treatment with investigations suggesting a thyroiditic mechanism rather than Graves\u2019 disease, and a high frequency of subsequent hypothyroidism. Any thyroid abnormality occurred in 23\u00b70% following ipilimumab, 39\u00b71% following a\n PD<\/jats:styled-content>\n \u20101 inhibitor and 50% following combination treatment. Abnormal thyroid function was more common in female patients.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Thyroid dysfunction occurs commonly in patients with melanoma treated with immune checkpoint inhibitors, with rates, including subclinical dysfunction, occurring in up to 50%.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cen.13297","type":"journal-article","created":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T20:52:40Z","timestamp":1482871960000},"page":"614-620","source":"Crossref","is-referenced-by-count":164,"title":["Thyroid abnormalities following the use of cytotoxic T\u2010lymphocyte antigen\u20104 and programmed death receptor protein\u20101 inhibitors in the treatment of melanoma"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1565-8617","authenticated-orcid":false,"given":"D.L.","family":"Morganstein","sequence":"first","affiliation":[{"name":"Skin Unit Royal Marsden Hospital London UK"},{"name":"Department of Endocrinology Chelsea and Westminster Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Lai","sequence":"additional","affiliation":[{"name":"Skin Unit Royal Marsden Hospital London UK"},{"name":"Department of Endocrinology Chelsea and Westminster Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Spain","sequence":"additional","affiliation":[{"name":"Skin Unit Royal Marsden Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Diem","sequence":"additional","affiliation":[{"name":"Skin Unit Royal Marsden Hospital London UK"},{"name":"Department of Oncology\/Hematology Cantonal Hospital St. Gallen Switzerland Switzerland"},{"name":"Department of Oncology\/Hematology Hospital Grabs Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Royal Marsden Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mace","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Chelsea and Westminster Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gore","sequence":"additional","affiliation":[{"name":"Skin Unit Royal Marsden Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Larkin","sequence":"additional","affiliation":[{"name":"Skin Unit Royal Marsden Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104621"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70122-1"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611299"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503093"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0845"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2306"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0499"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0b013e3181ef72a1"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414428"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4560"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2300"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1740-8261.2009.01649.x"},{"key":"e_1_2_5_16_1","volume-title":"Radiopharmaceuticals 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