{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:40:50Z","timestamp":1782510050521,"version":"3.54.5"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Japan Society"},{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["19K23942"],"award-info":[{"award-number":["19K23942"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["25K19669"],"award-info":[{"award-number":["25K19669"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with immune-related adverse events (irAEs), including pituitary dysfunction. Combination immunotherapy with PD-1 and CTLA-4 inhibitors increases the risk of pituitary irAEs compared to PD-1 monotherapy; however, their detailed characteristics remain unclear. We aimed to clarify the clinical features of pituitary irAEs induced by combination immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>In this retrospective cohort study, we compared patients treated with combination therapy of nivolumab and ipilimumab (Nivo\/Ipi) to those receiving nivolumab monotherapy (Nivo). We analyzed clinical data including presenting symptoms, laboratory findings, pituitary MRI results, and coexisting irAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pituitary irAEs were more frequent in the Nivo\/Ipi group (17.4%) than in the Nivo group (2.7%) and developed earlier (median onset: 63 vs 153 days, respectively). All 15 patients in the Nivo group presented with isolated ACTH deficiency (IAD), whereas the Nivo\/Ipi group included 8 cases of IAD and 8 cases of combined pituitary hormone deficiency (CPHD). In the Nivo\/Ipi group, CPHD occurred significantly earlier than IAD (median onset: 40 vs 84 days) and was associated with a higher incidence of headache and pituitary swelling on MRI. Furthermore, 75% of patients with CPHD also experienced non-endocrine irAEs. Two CPHD patients experienced worsening of symptoms and pituitary dysfunction following re-administration of Nivo\/Ipi.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pituitary irAEs are more frequent and develop earlier in patients receiving Nivo\/Ipi. CPHD and IAD, induced by this combination immunotherapy, exhibit distinct clinical courses. Recognizing these differences is crucial for the optimal management of pituitary irAEs during combination immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag031","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T12:46:29Z","timestamp":1770986789000},"page":"254-263","source":"Crossref","is-referenced-by-count":1,"title":["Distinct patterns of pituitary dysfunction in combination immunotherapy with nivolumab and ipilimumab"],"prefix":"10.1093","volume":"194","author":[{"given":"Aya","family":"Sakurai","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 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Sakyo-ku, Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-2784","authenticated-orcid":false,"given":"Yohei","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4330-2370","authenticated-orcid":false,"given":"Daisuke","family":"Taura","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology 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