{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:57Z","timestamp":1784557017032,"version":"3.55.0"},"reference-count":21,"publisher":"Bioscientifica","issue":"11","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,30]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The aim of this study was to define functional and anatomical pituitary disease at the time of presentation following immune checkpoint inhibitor (ICI) therapy and to describe any changes in pituitary function over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective observational audit of patients on ICI therapy at our centre between January 2013 and September 2023. We reviewed all patients on ICI therapy under the care of the oncology department at University Hospital Plymouth, a 1000-bedded hospital serving a population of 500,000 people. From this group, we identified all individuals referred to the endocrinology department with a suspected diagnosis of adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. People were included if they had pituitary disease, as evidenced by low ACTH, other pituitary dysfunction and\/or abnormalities on pituitary imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine hundred and fifty-four patients received ICI therapy during the study period, and 37 (a prevalence of 3.9%) developed hypothalamic\u2013pituitary\u2013adrenal axis dysfunction. Their mean age was 65 years, and 70% were male. About 86.5% of the total patients affected were treated for metastatic malignancies. Ten of the 37 patients died during follow-up as a direct consequence or complication of their primary cancer diagnosis. The median interval for the onset of symptoms was 4 months. Following repeated testing, there was no recovery in cortisol or ACTH levels for any individual. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target the corticotrophs, with no evidence of recovery over time. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, which appeared to be a particular feature of immune-mediated hypophysitis. These were confined to the anterior aspect of the pituitary gland, appearing as striations, and were not visible on any of the scans performed more than 3 months after the likely onset of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data show that immune-related hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary that are richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and, therefore, cortisol production.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-24-0223","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T12:25:53Z","timestamp":1727699153000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":7,"title":["Immune checkpoint inhibitor induced hypophysitis: a specific disease of corticotrophs?"],"prefix":"10.1530","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-0001","authenticated-orcid":true,"given":"Nishchil","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kagabo","family":"Hirwa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Pearce","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinny","family":"Jeffery","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fizzah","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1833-1276","authenticated-orcid":true,"given":"Daniel","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Cancer Medicine","first-page":"6585","article-title":"Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma","volume":"8","author":"Kassi","year":"2019","unstructured":"Kassi EAngelousi AAsonitis NDiamantopoulos PAnastasopoulou APapaxoinis GKokkinos MGiovanopoulos IKyriakakis GPetychaki F, et al. 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Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline. European Journal of Endocrinology 2022 187 G1\u2013G21. (https:\/\/doi.org\/10.1530\/EJE-22-0689)"},{"key":"bib7","series-title":"Endocrine Connections","first-page":"G1","article-title":"Society for endocrinology endocrine emergency guidance: acute management of the endocrine complications of checkpoint inhibitor therapy","volume":"7","author":"Higham","year":"2018","unstructured":"Higham CEOlsson-Brown ACarroll PCooksley TLarkin JLorigan PMorganstein DTrainer PJ & Society for Endocrinology Clinical Committee. Society for endocrinology endocrine emergency guidance: acute management of the endocrine complications of checkpoint inhibitor therapy. Endocrine Connections 2018 7 G1\u2013G7. (https:\/\/doi.org\/10.1530\/EC-18-0068)"},{"key":"bib8","series-title":"Journal of Clinical Medicine","first-page":"3468","article-title":"Tan H. Progress and challenges of immune checkpoint inhibitor-induced hypophysitis","volume":"12","author":"Chen","year":"2023","unstructured":"Chen PLi J & Tan H. Tan H. Progress and challenges of immune checkpoint inhibitor-induced hypophysitis. Journal of Clinical Medicine 2023 12 3468. (https:\/\/doi.org\/10.3390\/jcm12103468)"},{"key":"bib9","series-title":"European Journal of Endocrinology","first-page":"211","article-title":"Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis","volume":"181","author":"Faje","year":"2019","unstructured":"Faje AReynolds KZubiri LLawrence DCohen JVSullivan RJNachtigall L & Tritos N. Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis. European Journal of Endocrinology 2019 181 211\u2013219. (https:\/\/doi.org\/10.1530\/EJE-19-0238)"},{"key":"bib10","series-title":"Frontiers in Endocrinology (Lausanne)","first-page":"1091185","article-title":"Frequency and clinical characteristics of hypophysitis and hypopituitarism in patients undergoing immunotherapy - A systematic review","volume":"14","author":"Jacques","year":"2023","unstructured":"Jacques JPValadares LPMoura ACOliveira MRF & Naves LA. Frequency and clinical characteristics of hypophysitis and hypopituitarism in patients undergoing immunotherapy - A systematic review. Frontiers in Endocrinology (Lausanne) 2023 14 1091185. (https:\/\/doi.org\/10.3389\/fendo.2023.1091185)"},{"key":"bib11","series-title":"Frontiers in Oncology","first-page":"836859","article-title":"Immune checkpoint inhibitor-induced hypophysitis and patterns of loss of pituitary function","volume":"12","author":"Jessel","year":"2022","unstructured":"Jessel SWeiss SAAustin MMahajan AEtts KZhang LAizenbud LPerdigoto ALHurwitz MSznol M, et al. Immune checkpoint inhibitor-induced hypophysitis and patterns of loss of pituitary function. Frontiers in Oncology 2022 12 836859. (https:\/\/doi.org\/10.3389\/fonc.2022.836859)"},{"key":"bib12","series-title":"Journal of the National Comprehensive Cancer Network","first-page":"281","article-title":"Hypophysitis and secondary adrenal insufficiency from immune checkpoint inhibitors: diagnostic challenges and link with survival","volume":"21","author":"Johnson","year":"2023","unstructured":"Johnson JGoldner WAbdallah DQiu FGanti AK & Kotwal A. Hypophysitis and secondary adrenal insufficiency from immune checkpoint inhibitors: diagnostic challenges and link with survival. Journal of the National Comprehensive Cancer Network 2023 21 281\u2013287. (https:\/\/doi.org\/10.6004\/jnccn.2022.7098)"},{"key":"bib13","series-title":"Journal of Investigative Medicine","first-page":"939","article-title":"Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort","volume":"70","author":"Kotwal","year":"2022","unstructured":"Kotwal ARouleau SGDasari SKottschade LRyder MKudva YCMarkovic S & Erickson D. Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort. Journal of Investigative Medicine 2022 70 939\u2013946. (https:\/\/doi.org\/10.1136\/jim-2021-002099)"},{"key":"bib14","series-title":"Cancer Management and Research","first-page":"9551","article-title":"Managing ipilimumab-induced hypophysitis: challenges and current therapeutic strategies","volume":"12","author":"Tsoli","year":"2020","unstructured":"Tsoli MKaltsas GAngelousi AAlexandraki KRandeva H & Kassi E. Managing ipilimumab-induced hypophysitis: challenges and current therapeutic strategies. Cancer Management and Research 2020 12 9551\u20139561. (https:\/\/doi.org\/10.2147\/CMAR.S224791)"},{"key":"bib15","series-title":"Medical Oncology","first-page":"243","article-title":"Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events","volume":"40","author":"Meybodi","year":"2023","unstructured":"Meybodi SMFarasati Far BPourmolaei ABaradarbarjastehbaf FSafaei MMohammadkhani N & Samadani AA. Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events. Medical Oncology 2023 40 243. 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(https:\/\/doi.org\/10.1210\/jendso\/bvad012)"},{"key":"bib17","series-title":"Frontiers in Endocrinology (Lausanne)","first-page":"1295865","article-title":"Imaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis","volume":"14","author":"Galligan","year":"2023","unstructured":"Galligan AIravani ALasocki AWallace RWeppler AMSachithanandan NChiang CColman PGWentworth JSpain L, et al. Imaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis. Frontiers in Endocrinology (Lausanne) 2023 14 1295865. 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(https:\/\/doi.org\/10.1016\/j.currproblcancer.2020.100644)"},{"key":"bib20","series-title":"AJNR. American Journal of Neuroradiology","first-page":"1751","article-title":"Ipilimumab-induced hypophysitis: MR imaging findings","volume":"30","author":"Carpenter","year":"2009","unstructured":"Carpenter KJMurtagh RDLilienfeld HWeber J & Murtagh FR. Ipilimumab-induced hypophysitis: MR imaging findings. AJNR. American Journal of Neuroradiology 2009 30 1751\u20131753. (https:\/\/doi.org\/10.3174\/ajnr.A1623)"},{"key":"bib21","series-title":"Endotext [Internet]","article-title":"Development and microscopic anatomy of the pituitary gland","author":"Larkin","year":"2000","unstructured":"Larkin S & Ansorge O. Development and microscopic anatomy of the pituitary gland. In Endotext [Internet] Eds Feingold KRAnawalt BBlackman MRBoyce AChrousos GCorpas Ede Herder WWDhatariya KDungan KHofland J, et al. South Dartmouth, MA, USA: MD. Text.com, Inc., 2000."}],"container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/13\/11\/EC-24-0223.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/13\/11\/EC-24-0223.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/13\/11\/EC-24-0223.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:47:20Z","timestamp":1784555240000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/1629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,30]]},"references-count":21,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.1530\/ec-24-0223","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,30]]}}}