{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:32:29Z","timestamp":1789842749308,"version":"4.0.1"},"reference-count":16,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Acquired generalized lipodystrophy (AGL) is rarely associated with immune checkpoint inhibitors (ICIs). A few cases report associations with inhibitors to programmed cell death protein 1 (PD-1 inhibitors); however, association with combined immunotherapies has not been reported. We present a 48-year-old female with recurrent malignant melanoma who underwent 23 cycles of nivolumab, a PD-1 inhibitor, and 11 cycles of combined cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitor and PD-1 inhibitor ipilimumab-nivolumab. During the latter course of combination therapy, she experienced progressive weight loss and a dramatic change in body habitus over 3 to 6 months. Physical examination showed generalized loss of subcutaneous fat with protruding veins and muscular definition. Metabolic workup showed new-onset diabetes mellitus, a very low high-density lipoprotein, severe hypertriglyceridemia, and undetectable leptin\/adiponectin levels. Whole-body fluorodeoxyglucose positron emission tomography performed for restaging and response assessment revealed generalized soft tissue edema and diffuse hepatic steatosis. An excisional skin biopsy identified changes consistent with involutional lipoatrophy\/lipodystrophy. Treatment included insulin (average total daily dose 0.13-0.26 Units\/kg\/day) and a combination of lipid-lowering therapy (statins, fenofibrate, icosapent ethyl), which led to marked improvement in triglycerides and symptoms. This case further underscores the emerging challenges with endocrinopathies associated with checkpoint inhibitors.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf023","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T04:22:46Z","timestamp":1737606166000},"source":"Crossref","is-referenced-by-count":6,"title":["Acquired Generalized Lipodystrophy as an Adverse Event of Combined Immune Checkpoint Inhibitor Therapy"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1236-4939","authenticated-orcid":false,"given":"Randol","family":"Kennedy","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Duke University Medical Center , Durham, NC 27710-1000 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin Rei L","family":"Macrohon","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Makati Medical Center , Makati City 1229 ,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Lourdes Grace V","family":"David","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Makati Medical Center , Makati City 1229 ,","place":["Philippines"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meg","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Duke University Medical Center , Durham, NC 27710-1000 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April K S","family":"Salama","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Duke University Medical Center , Durham, NC 27710-1000 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afreen","family":"Shariff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Duke University Medical Center , Durham, NC 27710-1000 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"issue":"12","key":"2025021712071267700_luaf023-B1","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2025021712071267700_luaf023-B2","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"},{"issue":"1","key":"2025021712071267700_luaf023-B3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2337\/db21-1086","article-title":"Characterization and clinical association of autoantibodies against perilipin 1 in patients with acquired generalized lipodystrophy","volume":"72","author":"Corvillo","year":"2023","journal-title":"Diabetes"},{"issue":"3","key":"2025021712071267700_luaf023-B4","doi-asserted-by":"crossref","first-page":"104073","DOI":"10.1016\/j.lpm.2021.104073","article-title":"Autoimmunity in lipodystrophy syndromes","volume":"50","author":"Ceccarini","year":"2021","journal-title":"Presse Med"},{"issue":"10","key":"2025021712071267700_luaf023-B5","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.2337\/dc18-2535","article-title":"Acquired generalized lipodystrophy: a new cause of anti-PD-1 immune-related diabetes","volume":"42","author":"Jehl","year":"2019","journal-title":"Diabetes Care"},{"issue":"1","key":"2025021712071267700_luaf023-B6","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.4158\/ACCR-2019-0234","article-title":"A case of acquired generalized lipodystrophy associated with pembrolizumab in a patient with metastatic malignant melanoma","volume":"6","author":"Bedrose","year":"2020","journal-title":"AACE Clin Case Rep"},{"issue":"2","key":"2025021712071267700_luaf023-B7","doi-asserted-by":"crossref","first-page":"luad025","DOI":"10.1210\/jcemcr\/luad025","article-title":"Marked hypoleptinemia precedes overt fat loss in immune checkpoint inhibitor-induced acquired generalized lipodystrophy","volume":"1","author":"Dhanasekaran","year":"2023","journal-title":"JCEM Case Rep"},{"issue":"8","key":"2025021712071267700_luaf023-B8","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1210\/jc.2018-02221","article-title":"Acquired lipodystrophy associated with nivolumab in a patient with advanced renal cell carcinoma","volume":"104","author":"Falcao","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2025021712071267700_luaf023-B9","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7326\/L19-0635","article-title":"Lipodystrophic nonalcoholic fatty liver disease induced by immune checkpoint blockade","volume":"172","author":"Eigentler","year":"2020","journal-title":"Ann Intern Med"},{"issue":"6","key":"2025021712071267700_luaf023-B10","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.eprac.2024.03.023","article-title":"Endocrinopathies associated with immune checkpoint inhibitor use","volume":"30","author":"Kotwal","year":"2024","journal-title":"Endocr Pract"},{"issue":"4","key":"2025021712071267700_luaf023-B11","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ecl.2016.06.012","article-title":"Lipodystrophy syndromes","volume":"45","author":"Hussain","year":"2016","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"8","key":"2025021712071267700_luaf023-B12","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1056\/NEJMoa012437","article-title":"Leptin-replacement therapy for lipodystrophy","volume":"346","author":"Oral","year":"2002","journal-title":"N Engl J Med"},{"issue":"9","key":"2025021712071267700_luaf023-B13","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s40265-013-0074-7","article-title":"Metreleptin: first global approval","volume":"73","author":"Chou","year":"2013","journal-title":"Drugs"},{"issue":"6","key":"2025021712071267700_luaf023-B14","doi-asserted-by":"crossref","first-page":"922","DOI":"10.4158\/EP11229.OR","article-title":"Clinical effects of long-term metreleptin treatment in patients with lipodystrophy","volume":"17","author":"Chan","year":"2011","journal-title":"Endocr Pract"},{"issue":"3","key":"2025021712071267700_luaf023-B15","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s12020-018-1589-1","article-title":"Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy","volume":"60","author":"Brown","year":"2018","journal-title":"Endocrine"},{"issue":"1","key":"2025021712071267700_luaf023-B16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/cen.12980","article-title":"Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy","volume":"85","author":"Chan","year":"2016","journal-title":"Clin Endocrinol (Oxf)"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/3\/luaf023\/61817635\/luaf023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/3\/luaf023\/61817635\/luaf023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T12:07:25Z","timestamp":1739794045000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luaf023\/8006263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,2,10]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luaf023","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,2,10]]},"article-number":"luaf023"}}