{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:30:05Z","timestamp":1789695005788,"version":"4.0.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs), by unleashing the anticancer response of the immune system, can improve survival of patients affected by several malignancies, but may trigger a broad spectrum of adverse events, including autoimmune hypophysitis. ICI-related hypophysitis mainly manifests with anterior hypopituitarism, while the simultaneous involvement of both anterior and posterior pituitary (i.e., panhypophysitis) has rarely been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>In June 2015, a 64-year-old man affected by liver metastases of a uveal melanoma was referred to us due to polyuria and polydipsia. Two months prior, he had started ipilimumab therapy (3 mg\/kg iv every 21 days). The treatment was well-tolerated (only mild asthenia and diarrhea were reported). A few days before the fourth cycle, the patient complained of intense headaches, profound fatigue, nocturia, polyuria (up to 10 L urine\/daily), and polydipsia. Laboratory tests were consistent with adrenal insufficiency, hypothyroidism, and transient central diabetes insipidus. The pituitary MRI showed an enlarged gland with microinfarcts, while the hypophyseal stalk was normal, and the neurohypophyseal \u2018bright signal\u2019 in T1 sequences was not detected. The treatment included dexamethasone (then cortisone acetate at replacement dose), desmopressin, and levothyroxine. Within the next five days, the symptoms resolved, and blood pressure, electrolytes, glucose, and urinalysis were stable within the normal ranges; desmopressin was discontinued while cortisone acetate and levothyroxine were maintained. The fourth ipilimumab dose was entirely administered in the absence of further side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As ICIs are increasingly used as anticancer agents, the damage to anterior and\/or posterior pituitary can be progressively encountered by oncologists and endocrinologists in their clinical practice. Patients on ICIs and their caregivers should be informed about that risk and be empowered to alert the referring specialists early, at the onset of panhypopituitarism symptoms, including polyuria\/polydipsia.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2020.582394","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T07:40:48Z","timestamp":1606808448000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Case Report: Ipilimumab-Induced Panhypophysitis: An Infrequent Occurrence and Literature Review"],"prefix":"10.3389","volume":"10","author":[{"given":"Agnese","family":"Barnabei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carpano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonsina","family":"Chiefari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bianchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Lauretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilda","family":"Mormando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilia","family":"Puliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Paoletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialuisa","family":"Appetecchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Torino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2019-0087","article-title":"The emerging use of immune checkpoint blockade in the adjuvant setting for solid tumors: a review","volume":"11","author":"Moujaess","year":"2019","journal-title":"Immunotherapy"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1210\/er.2018-00006","article-title":"Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints","volume":"40","author":"Chang","year":"2019","journal-title":"Endocr Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1210\/er.2004-0011","article-title":"Autoimmune Hypophysitis","volume":"26","author":"Caturegli","year":"2005","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1714","article-title":"A radiologic score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively","volume":"30","author":"Gutenberg","year":"2009","journal-title":"AJNR Am J Neuroradiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s11547-019-01120-x","article-title":"Imaging findings in hypophysitis: a review","volume":"125","author":"Caranci","year":"2020","journal-title":"Radiol Med"},{"key":"B7","first-page":"p. 751","volume-title":"Clinical Physiology of Acid-Base and Electrolyte Disorders","author":"Rose","year":"2001"},{"key":"B8","unstructured":"Clinical manifestations and causes of central diabetes insipidus\n            BichetDG"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2001.2.4.222","article-title":"MR Imaging of Central Diabetes Insipidus: A Pictorial Essay","volume":"2","author":"Shin","year":"2001","journal-title":"Korean J Radiol"},{"key":"B10","unstructured":"BichetDG\n          Treatment of central diabetes insipidus"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-018-9480-1","article-title":"Primary hypophysitis and other autoimmune disorders of the sellar and suprasellar regions","volume":"19","author":"Gubbi","year":"2018","journal-title":"Rev Endocr Metab Disord"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0434","article-title":"Endocrine side-effects of anti-cancer drugs: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses","volume":"169","author":"Torino","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1634\/theoncologist.2018-0470","article-title":"Endocrine-Related Adverse Events Related to Immune Checkpoint Inhibitors: Proposed Algorithms for Management","volume":"25","author":"Del Rivero","year":"2020","journal-title":"Oncologist"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-020-01226-4","article-title":"Immune checkpoint inhibitor-associated pituitary adverse events: an observational, retrospective, disproportionality study","volume":"43","author":"Bai","year":"2020","journal-title":"J Endocrinol Invest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.41.6750","article-title":"Management of immune-related adverse events and kinetics of response with ipilimumab","volume":"30","author":"Weber","year":"2012","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4075","article-title":"Endocrine side effects induced by immune checkpoint inhibitors","volume":"98","author":"Corsello","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2213-y","article-title":"Ipilimumab-induced endocrinopathies: when to start corticosteroids (or not)","volume":"72","author":"Corsello","year":"2013","journal-title":"Cancer Chemother Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s11102-009-0193-z","article-title":"Anti-CTLA-4 Antibody Therapy Associated Autoimmune Hypophysitis: Serious Immune-Related Adverse Events Across a Spectrum of Cancer Subtypes","volume":"13","author":"Dillard","year":"2010","journal-title":"Pituitary"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2014.0105","article-title":"Ipilimumab-induced hypophysitis and uveitis in a patient with metastatic melanoma and a history of ipilimumab-induced skin rash","volume":"12","author":"Nallapaneni","year":"2014","journal-title":"J Natl Compr Canc Netw"},{"key":"B21","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1530\/EDM-17-0146","article-title":"Combination immune checkpoint inhibitor therapy nivolumab and ipilimumab associated with multiple endocrinopathies","volume":"2018","author":"Gunawan","year":"2018","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01905","article-title":"Anti-PD-L1 treatment-induced central diabetes insipidus","volume":"103","author":"Zhao","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106427","article-title":"Central diabetes insipidus related to anti-PD1 protein active immunotherapy","volume":"83","author":"Deligiorgi","year":"2020","journal-title":"Int Immunopharm"},{"key":"B24","doi-asserted-by":"publisher","first-page":"S2359","DOI":"10.20945\/2359-3997000000221","article-title":"Permanent diabetes insipidus in a patient with mesothelioma treated with immunotherapy","volume":"6","author":"Brilli","year":"2020","journal-title":"Arch Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31200","article-title":"Endocrine dysfunction induced by immune checkpoint inhibitors: practical recommendations for diagnosis and clinical management","volume":"124","author":"Barroso-Sousa","year":"2018","journal-title":"Cancer"},{"key":"B26","doi-asserted-by":"publisher","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":"B27","doi-asserted-by":"publisher","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":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nature01621","article-title":"Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease","volume":"423","author":"Ueda","year":"2003","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1146\/annurev-med-053013-053944","article-title":"Pharmacogenetics of cancer drugs","volume":"66","author":"Hertz","year":"2015","journal-title":"Annu Rev Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14609","article-title":"Pharmacogenetics for severe adverse drug reactions induced by molecular-targeted therapy","volume":"111","author":"Udagawa","year":"2020","journal-title":"Cancer Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-019-00845-w","article-title":"Germinal Immunogenetics predict treatment outcome for PD-1\/PD-L1 checkpoint inhibitors","volume":"38","author":"Refae","year":"2020","journal-title":"Invest New Drugs"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0074-1","article-title":"Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients","volume":"118","author":"Bins","year":"2018","journal-title":"Br J Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.582394\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T07:40:51Z","timestamp":1606808451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2020.582394\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":33,"alternative-id":["10.3389\/fonc.2020.582394"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.582394","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,1]]},"article-number":"582394"}}