{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:12:45Z","timestamp":1789560765746,"version":"build-2803163510"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"Suppl 2","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, including malignant melanoma. However, ICIs are associated with immune-related adverse events (irAEs), including hypophysitis, secondary adrenal insufficiency, thyroid disorders, and insulin-dependent diabetes. We present the case of a 60-year-old male with a history of autoimmune disorders, including primary hypothyroidism and giant-cell arteritis, who developed diabetes mellitus requiring insulin therapy after 6 weeks of treatment, eosinophilic asthma after 10 weeks, and who was admitted after 28 weeks of therapy with secondary adrenal insufficiency due to suspected ICI-associated isolated adrenocorticotrophic hormone (ACTH) deficiency. Pituitary magnetic resonance imaging showed no abnormalities. After several surgeries for melanoma and basal cell carcinoma, his current treatment includes hydrocortisone, levothyroxine, and insulin therapy. This case highlights the complexities in diagnosing and managing endocrinopathies associated with ICI therapy. As ICIs become more widely used, endocrine irAEs such as hypophysitis and isolated ACTH deficiency are expected to become increasingly common. A multidisciplinary approach is key to minimizing complications. While endocrine irAEs may require prompt hormone replacement, they rarely justify discontinuation of ICI therapy, whose benefits often outweigh the risks.<\/jats:p>","DOI":"10.4103\/aam.aam_658_25","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:00:10Z","timestamp":1785484810000},"page":"S347-S351","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Secondary Adrenal Insufficiency and Multisystem Endocrinopathy Following Immune Checkpoint Inhibitor Therapy"],"prefix":"10.4103","volume":"25","author":[{"given":"Olga","family":"Fedorova","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Mediclinic Parkview Hospital, Mediclinic Middle East, Dubai, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuad","family":"AlSaraj","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Mediclinic Parkview Hospital, Mediclinic Middle East, Dubai, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"R1-20260916","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11102-015-0671-4","article-title":"Immunotherapy and hypophysitis: Clinical presentation, treatment, and biologic insights","volume":"19","author":"Faje","year":"2016","journal-title":"Pituitary"},{"key":"R2-20260916","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s40618-019-01112-8","article-title":"Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: Results of a large multicentre study","volume":"43","author":"Presotto","year":"2020","journal-title":"J Endocrinol Invest"},{"key":"R3-20260916","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis","volume":"4","author":"Barroso-Sousa","year":"2018","journal-title":"JAMA Oncol"},{"key":"R4-20260916","doi-asserted-by":"crossref","first-page":"1369268","DOI":"10.3389\/fendo.2024.1369268","article-title":"Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival","volume":"15","author":"Yang","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R5-20260916","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"},{"key":"R6-20260916","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1210\/clinem\/dgab672","article-title":"Hypophysitis, the growing spectrum of a rare pituitary disease","volume":"107","author":"Langlois","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"R7-20260916","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1016\/j.ajpath.2016.08.020","article-title":"Hypophysitis secondary to cytotoxic T-lymphocyte-associated protein 4 blockade: Insights into pathogenesis from an autopsy series","volume":"186","author":"Caturegli","year":"2016","journal-title":"Am J Pathol"},{"key":"R8-20260916","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/pin.13161","article-title":"An autopsy case study of lymphocytic hypophysitis induced by nivolumab treatment for esophageal malignant melanoma","volume":"71","author":"Okabe","year":"2021","journal-title":"Pathol Int"},{"key":"R9-20260916","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"},{"key":"R10-20260916","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-22-0689","article-title":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","volume":"187","author":"Husebye","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"R11-20260916","doi-asserted-by":"crossref","first-page":"e220513","DOI":"10.1530\/EC-22-0513","article-title":"Diagnostic criteria and proposed management of immune-related endocrinopathies following immune checkpoint inhibitor therapy for cancer","volume":"12","author":"Percik","year":"2023","journal-title":"Endocr Connect"},{"key":"R12-20260916","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.eprac.2022.04.010","article-title":"American Association of Clinical Endocrinology disease state clinical review: Evaluation and management of immune checkpoint inhibitor-mediated endocrinopathies: A practical case-based clinical approach","volume":"28","author":"Yuen","year":"2022","journal-title":"Endocr Pract"},{"key":"R13-20260916","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1002\/cncr.31629","article-title":"High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma","volume":"124","author":"Faje","year":"2018","journal-title":"Cancer"},{"key":"R14-20260916","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejca.2019.03.002","article-title":"Immune checkpoint inhibitor-associated hypophysitis-World Health Organisation vigibase report analysis","volume":"113","author":"Guerrero","year":"2019","journal-title":"Eur J Cancer"},{"key":"R15-20260916","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.3390\/jcm12103468","article-title":"Progress and challenges of immune checkpoint inhibitor-induced hypophysitis","volume":"12","author":"Chen","year":"2023","journal-title":"J Clin 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