{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:38Z","timestamp":1784556998530,"version":"3.55.0"},"reference-count":36,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"Summary<\/jats:title>\n \n Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab \u2013 a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16\u200a\u03bcIU\/ml (normal 0.3\u20134.7); free tri-iodothyronine (T\n 3<\/jats:sub>\n ) was markedly elevated at 1031\u200apg\/dl (normal 249\u2013405), as was free thyroxine (T\n 4<\/jats:sub>\n ) at 5.6\u200ang\/dl (normal 0.8\u20131.6). With iopanoic acid and methimazole therapy, she markedly improved within 48\u200ah, which could be attributed to lowering of serum T\n 3<\/jats:sub>\n with iopanoic acid rather than to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of T\n 4<\/jats:sub>\n -to-T\n 3<\/jats:sub>\n conversion.\n <\/jats:p>\n \n Learning points<\/jats:title>\n \n \n \n While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome.<\/jats:p>\n <\/jats:list-item>\n \n Immune-related adverse reactions usually occur after 1\u20133 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab.<\/jats:p>\n <\/jats:list-item>\n \n Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/edm-14-0092","type":"journal-article","created":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T05:56:05Z","timestamp":1424066165000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":13,"title":["A novel melanoma therapy stirs up a storm: ipilimumab-induced thyrotoxicosis"],"prefix":"10.1530","volume":"2015","author":[{"given":"Christine","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, Los Angeles, California, 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inder J","family":"Chopra","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, University of California, 757 Westwood Plaza Blvd, Suite 7501, Los Angeles, CA, 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, Los Angeles, California, 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref311","first-page":"1816","article-title":"Jod-Basedow syndrome following oral iodine and radioiodinated-antibody administration","volume":"38","year":"1997","journal-title":"Journal of Nuclear Medicine"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1089\/thy.2011.0334","article-title":"Diagnostic criteria and clinico-epidemiological features of thyroid storm based on a nationwide survey","volume":"22","year":"2012","journal-title":"Thyroid"},{"key":"ref301","first-page":"15s","article-title":"Evaluation of the effect of systemic corticosteroids for the treatment of immune-related adverse events (irAEs) on the development or maintenance of ipilimumab clinical activity","volume":"27","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1158\/1078-0432.CCR-09-1024","article-title":"A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma","volume":"15","year":"2009","journal-title":"Clinical Cancer Research"},{"key":"ref131","first-page":"1816","article-title":"Jod-Basedow syndrome following oral iodine and radioiodinated-antibody administration","volume":"38","year":"1997","journal-title":"Journal of Nuclear Medicine"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1089\/thy.2012.2207.ed1","article-title":"Clinical criteria for the diagnosis of thyroid storm","volume":"22","year":"2012","journal-title":"Thyroid"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1470-2045(09)70334-1","article-title":"Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomized, double-blind, multicentre, phase 2, dose-ranging study","volume":"11","year":"2010","journal-title":"Lancet. 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