{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:48:45Z","timestamp":1781534925365,"version":"3.54.5"},"reference-count":38,"publisher":"Korean Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP 23K24386"],"award-info":[{"award-number":["JP 23K24386"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-enm.org"],"crossmark-restriction":true},"short-container-title":["Endocrinol Metab"],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:p>Background: Anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) monotherapy induces two types of pituitary immunerelated adverse events (irAEs): multiple pituitary hormone deficiency (Multi-D; impairment of \u22652 anterior pituitary hormones) and isolated adrenocorticotropic hormone (ACTH) deficiency (IAD). Combination therapy with CTLA-4-Ab and anti-programmed cell death-1 antibody (PD-1\/CTLA-4-Abs), which is increasingly replacing CTLA-4-Ab monotherapy, frequently causes pituitary irAEs; however, whether it increases Multi-D\/IAD incidence is unknown.Methods: In total, 74 and 748 patients with malignancies treated with PD-1\/CTLA-4-Abs and PD-1-Ab, respectively, were prospectively evaluated for ACTH and cortisol levels at baseline and every 6 weeks after treatment initiation, and then observed until the last clinical visit. The characteristics of pituitary irAEs were evaluated by pituitary stimulation tests and compared with those induced by PD-1-Ab monotherapy.Results: PD-1\/CTLA-4-Abs therapy showed higher incidence rates of pituitary irAEs (16\/74 [21.6%] vs. 25\/748 [3.3%], P&lt;0.001), Multi-D (9\/74 [12.2%] vs. 2\/748 [0.3%], P&lt;0.001), and IAD (7\/74 [9.5%] vs. 23\/748 [3.1%], P=0.014) than PD-1-Ab monotherapy. ACTH deficiency was observed in all cases, whereas the prevalence rates of luteinizing hormone deficiency (8\/16 [50.0%] vs. 1\/25 [4.0%]), follicle-stimulating hormone deficiency (6\/16 [37.5%] vs. 1\/25 [4.0%]), and thyrotropin deficiency (4\/16 [25.0%] vs. 0\/25 [0%]) were significantly higher after PD-1\/CTLA-4-Abs than after PD-1-Ab treatment. Pituitary enlargement, which was observed only in the Multi-D cases, was significantly more frequent after PD-1\/CTLA-4-Abs than after PD-1-Ab treatment (6\/16 [37.5%] vs. 0\/25 [0%], P=0.002).Conclusion: This prospective study revealed high risks of both Multi-D and IAD under PD-1\/CTLA-4-Abs treatment, emphasizing the need for careful evaluation of pituitary function.<\/jats:p>","DOI":"10.3803\/enm.2024.2180","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:09:34Z","timestamp":1739261374000},"page":"459-468","update-policy":"https:\/\/doi.org\/10.3803\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Combined PD-1 and CTLA-4 Blockade Increases the Risks of Multiple Pituitary Hormone Deficiency and Isolated Adrenocorticotropic Deficiency: A Prospective 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