{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T03:02:19Z","timestamp":1780110139022,"version":"3.54.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rev Endocr Metab Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immunotherapy-induced primary adrenal insufficiency (Ir-PAI) is a rare complication of immune checkpoint inhibitors (ICI). The clinical presentation is typically heterogeneous, with complex clinical pictures that may overlap with those of other endocrinopathies. Therefore, Ir-PAI may represent a life-threatening condition, with a possible subtle or acute onset, a high risk of electrolyte disorders, and hemodynamic instability. The management of Ir-PAI in cancer patients treated with ICIs requires a multidisciplinary management, involving at least oncologists and endocrinologists, to reach an early diagnosis, to safely manage patients, and to guarantee higher compliance and adherence to ICI treatment. In this study, we aimed to systematically examine cases of Ir-PAI reported in the literature and to describe our clinical experience. A total of 12 patients with Ir-PAI were collected from a systematic literature review, including cases reported from January 2011 to June 2025. Four patients were instead diagnosed at our Institution. Therefore, the evaluation of all 16 patients with Ir-PAIs identified 11 males (68.8%). Median age at PAI onset was 65 years (IQR: 18). The most common symptom at the occurrence of Ir-PAIs was asthenia\/fatigue in 13 patients (81.3%). Ir-PAIs occurred more frequently in patients treated with anti-PD-1 mAbs (9 cases, 56.3%), and the most prevalent primary tumors associated with Ir-PAIs were renal cell carcinomas in four patients (25%). Other concomitant endocrine toxicities in patients with Ir-PAIs were thyroid dysfunctions in 8 patients (50%), and hypogonadism in 2 patients (12.5%).<\/jats:p>\n                  <jats:p>Our systematic review shows that Ir-PAI is a rare but clinically relevant toxicity of ICIs.<\/jats:p>","DOI":"10.1007\/s11154-026-10058-1","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:16:44Z","timestamp":1780107404000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Primary adrenal insufficiency induced by immune checkpoint inhibitors (ICIs): a case series and systematic literature review"],"prefix":"10.1007","author":[{"given":"Sabrina","family":"Chiloiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Antonio","family":"De Sanctis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Parente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Giampietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"D\u2019Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Palluzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vertechy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Vita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Paris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"De Marinis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Iaconelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Schinzari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Tortora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Fagotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"issue":"17","key":"10058_CR1","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","volume":"36","author":"J Brahmer","year":"2018","unstructured":"Brahmer J, Lacchetti C, Schneider B, Atkins M, Brassil K, Caterino J, Chau I, Ernstoff M, Gardner J, Ginex P, Hallmeyer S, Chakrabarty J, Leighl N, Mammen J, McDermott D, Naing A, Nastoupil L, Phillips T, Porter L, Puzanov I, Reichner C, Santomasso B, Seigel C, Spira A, Suarez-Almazor M, Wang Y, Weber J, Wolchok J, Thompson J. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin oncology: official J Am Soc Clin Oncol. 2018;36(17):1714\u201368. https:\/\/doi.org\/10.1200\/JCO.2017.77.6385.","journal-title":"J Clin oncology: official J Am Soc Clin Oncol"},{"key":"10058_CR2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.tem.2021.10.009","volume":"33","author":"S Chiloiro","year":"2021","unstructured":"Chiloiro S, Bianchi A, Giampietro A, Milardi D, De Marinis L, Pontecorvi A. The changing clinical spectrum of endocrine adverse events in cancer immunotherapy. Trends Endocrinol Metabolism. 2021;33:87\u2013104. https:\/\/doi.org\/10.1016\/j.tem.2021.10.009.","journal-title":"Trends Endocrinol Metabolism"},{"key":"10058_CR3","doi-asserted-by":"publisher","first-page":"113365","DOI":"10.1016\/j.intimp.2024.113365","volume":"143 Pt 2","author":"M Hossain","year":"2024","unstructured":"Hossain M. A comprehensive review of immune checkpoint inhibitors for cancer treatment. Int Immunopharmacol. 2024;143 Pt 2:113365. https:\/\/doi.org\/10.1016\/j.intimp.2024.113365.","journal-title":"Int Immunopharmacol"},{"key":"10058_CR4","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.jaccao.2022.09.004","volume":"4","author":"S Tan","year":"2022","unstructured":"Tan S, Day D, Nicholls S, Segelov E. Immune Checkpoint Inhibitor Therapy in Oncology. JACC: CardioOncology. 2022;4:579\u201397. https:\/\/doi.org\/10.1016\/j.jaccao.2022.09.004.","journal-title":"JACC: CardioOncology"},{"key":"10058_CR5","doi-asserted-by":"publisher","unstructured":"Lee J, Ha S, Kim H. Clinical insights into novel immune checkpoint inhibitors. Front Pharmacol. 2021;12. https:\/\/doi.org\/10.3389\/fphar.2021.681320.","DOI":"10.3389\/fphar.2021.681320"},{"key":"10058_CR6","doi-asserted-by":"publisher","unstructured":"Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 2019;12. https:\/\/doi.org\/10.1186\/s13045-019-0779-5.","DOI":"10.1186\/s13045-019-0779-5"},{"key":"10058_CR7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.intimp.2018.06.001","volume":"62","author":"K Hargadon","year":"2018","unstructured":"Hargadon K, Johnson C, Williams C. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol. 2018;62:29\u201339. https:\/\/doi.org\/10.1016\/j.intimp.2018.06.001.","journal-title":"Int Immunopharmacol"},{"key":"10058_CR8","doi-asserted-by":"publisher","first-page":"451","DOI":"10.20892\/j.issn.2095-3941.2024.0055","volume":"21","author":"X Kong","year":"2024","unstructured":"Kong X, Zhang J, Chen S, Wang X, Xi Q, Shen H, Zhang R. Immune checkpoint inhibitors: breakthroughs in cancer treatment. Cancer Biology Med. 2024;21:451\u201372. https:\/\/doi.org\/10.20892\/j.issn.2095-3941.2024.0055.","journal-title":"Cancer Biology Med"},{"key":"10058_CR9","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1001\/jamaoncol.2016.1051","volume":"2 10","author":"C Friedman","year":"2016","unstructured":"Friedman C, Proverbs-Singh T, Postow M. Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors. Rev JAMA Oncol. 2016;2 10:1346\u201353. https:\/\/doi.org\/10.1001\/jamaoncol.2016.1051.","journal-title":"Rev JAMA Oncol"},{"key":"10058_CR10","doi-asserted-by":"publisher","unstructured":"Yin Q, Wu L, Han L, Zheng X, Tong R, Li L, Bai L, Bian Y. Immune-related adverse events of immune checkpoint inhibitors: a review. Front Immunol. 2023;14. https:\/\/doi.org\/10.3389\/fimmu.2023.1167975.","DOI":"10.3389\/fimmu.2023.1167975"},{"key":"10058_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41572-020-0160-6","volume":"6","author":"M Ramos-Casals","year":"2020","unstructured":"Ramos-Casals M, Brahmer J, Callahan M, Flores-Ch\u00e1vez A, Keegan N, Khamashta M, Lambotte O, Mariette X, Prat A, Suarez-Almazor M. Immune-related adverse events of checkpoint inhibitors. Nat Reviews Disease Primers. 2020;6:1\u201321. https:\/\/doi.org\/10.1038\/s41572-020-0160-6.","journal-title":"Nat Reviews Disease Primers"},{"key":"10058_CR12","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41573-021-00259-5","volume":"21","author":"R Sullivan","year":"2021","unstructured":"Sullivan R, Weber J. Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies. Nat Rev Drug Discovery. 2021;21:495\u2013508. https:\/\/doi.org\/10.1038\/s41573-021-00259-5.","journal-title":"Nat Rev Drug Discovery"},{"issue":"1","key":"10058_CR13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1210\/er.2018-00006","volume":"40","author":"L Chang","year":"2018","unstructured":"Chang L, Barroso-Sousa R, Tolaney S, Hodi F, Kaiser U, Min L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2018;40(1):17\u201365. https:\/\/doi.org\/10.1210\/er.2018-00006.","journal-title":"Endocr Rev"},{"issue":"7","key":"10058_CR14","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41574-021-00484-3","volume":"17","author":"JJ Wright","year":"2021","unstructured":"Wright JJ, Powers AC, Johnson DB. Endocrine toxicities of immune checkpoint inhibitors. Nat Rev Endocrinol. 2021;17(7):389\u201399. https:\/\/doi.org\/10.1038\/s41574-021-00484-3 . Epub 2021 Apr 19. PMID: 33875857; PMCID: PMC8769055.","journal-title":"Nat Rev Endocrinol"},{"key":"10058_CR15","doi-asserted-by":"publisher","unstructured":"Cardona Z, Sosman J, Chandra S, Huang W. Endocrine side effects of immune checkpoint inhibitors. Front Endocrinol. 2023;14. https:\/\/doi.org\/10.3389\/fendo.2023.1157805.","DOI":"10.3389\/fendo.2023.1157805"},{"key":"10058_CR16","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","volume":"4","author":"R Barroso-Sousa","year":"2017","unstructured":"Barroso-Sousa R, Barry W, Garrido-Castro A, Hodi F, Min L, Krop I, Tolaney S. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2017;4:173\u201382. https:\/\/doi.org\/10.1001\/jamaoncol.2017.3064.","journal-title":"JAMA Oncol"},{"key":"10058_CR17","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1007\/s12020-020-02355-9","volume":"69","author":"X Bai","year":"2020","unstructured":"Bai X, Lin X, Zheng K, Chen X, Wu X, Huang Y, Zhuang Y. Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse drug reaction database. VigiBase Endocr. 2020;69:670\u201381. https:\/\/doi.org\/10.1007\/s12020-020-02355-9.","journal-title":"VigiBase Endocr"},{"issue":"11","key":"10058_CR18","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1007\/s40618-022-01845-z","volume":"45","author":"D Lu","year":"2022","unstructured":"Lu D, Yao J, Yuan G, Gao Y, Zhang J, Guo X. Immune checkpoint inhibitor-associated new-onset primary adrenal insufficiency: a retrospective analysis using the FAERS. J Endocrinol Invest. 2022;45(11):2131\u20137. https:\/\/doi.org\/10.1007\/s40618-022-01845-z . Epub 2022 Jul 23. PMID: 35870109; PMCID: PMC9525402.","journal-title":"J Endocrinol Invest"},{"issue":"6","key":"10058_CR19","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1053\/j.seminoncol.2023.11.003","volume":"50","author":"S Martella","year":"2023","unstructured":"Martella S, Lucas M, Porcu M, Perra L, Denaro N, Pretta A, Deias G, Willard-Gallo K, Parra HS, Saba L, Scartozzi M, Wekking D, Kok M, Aiello MM, Solinas C. Primary adrenal insufficiency induced by immune checkpoint inhibitors: biological, clinical, and radiological aspects. Semin Oncol. 2023;50(6):144\u20138. Epub 2023 Dec 6. PMID: 38151399.","journal-title":"Semin Oncol"},{"key":"10058_CR20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1710","author":"S Bornstein","year":"2016","unstructured":"Bornstein S, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer G, Husebye E, Merke D, Murad M, Stratakis C, Torpy D. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016. https:\/\/doi.org\/10.1210\/jc.2015-1710. 101 2.","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"10058_CR21","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/joim.12162","volume":"275","author":"ES Husebye","year":"2014","unstructured":"Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, Falorni A, Gan EH, Hulting AL, Kasperlik-Zaluska A, K\u00e4mpe O, L\u00f8v\u00e5s K, Meyer G, Pearce SH. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014;275(2):104\u201315. https:\/\/doi.org\/10.1111\/joim.12162 . Epub 2013 Dec 16. PMID: 24330030.","journal-title":"J Intern Med"},{"key":"10058_CR22","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1097\/MED.0000000000000806","volume":"30","author":"V Siampanopoulou","year":"2023","unstructured":"Siampanopoulou V, Tasouli E, Angelousi A. Diagnostic strategies in adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2023;30:141\u201353. https:\/\/doi.org\/10.1097\/MED.0000000000000806.","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"10058_CR23","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.","journal-title":"BMJ"},{"issue":"4","key":"10058_CR24","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s42000-024-00535-0","volume":"23","author":"CC Spagnolo","year":"2024","unstructured":"Spagnolo CC, Campo I, Campenn\u00ec A, Cardile D, Cannav\u00f2 S, Silvestris N, Santarpia M, Ruggeri RM. Challenges and pitfalls in the management of endocrine toxicities from immune checkpoint inhibitors: a case presentation of synchronous thyrotoxicosis and primary adrenal insufficiency in a melanoma patient. Horm (Athens). 2024;23(4):759\u201364. https:\/\/doi.org\/10.1007\/s42000-024-00535-0 . Epub 2024 Feb 29. PMID: 38421588.","journal-title":"Horm (Athens)"},{"issue":"2","key":"10058_CR25","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1159\/000507652","volume":"13","author":"C Salinas","year":"2020","unstructured":"Salinas C, Renner A, Rojas C, Samtani S, Burotto M. Primary Adrenal Insufficiency during Immune Checkpoint Inhibitor Treatment: Case Reports and Review of the Literature. Case Rep Oncol. 2020;13(2):621\u20136. PMID: 32595473; PMCID: PMC7315192.","journal-title":"Case Rep Oncol"},{"issue":"8","key":"10058_CR26","doi-asserted-by":"publisher","first-page":"e16933","DOI":"10.7759\/cureus.16933","volume":"13","author":"N Figueroa-Perez","year":"2021","unstructured":"Figueroa-Perez N, Kashyap R, Bal D, Anjum Khan S, Pattan V, Autoimmune Myasthenia. Primary Adrenal Insufficiency, and Progressive Hypothyroidism Due to Pembrolizumab and Axitinib Combination Regimen. Cureus. 2021;13(8):e16933. https:\/\/doi.org\/10.7759\/cureus.16933 . PMID: 34513503; PMCID: PMC8412885.","journal-title":"Cureus"},{"key":"10058_CR27","doi-asserted-by":"publisher","unstructured":"Wang F, Shi X, Yu X, Yang Y. Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review. Front Endocrinol. 2024;15. https:\/\/doi.org\/10.3389\/fendo.2024.1326684.","DOI":"10.3389\/fendo.2024.1326684"},{"issue":"6","key":"10058_CR28","doi-asserted-by":"publisher","first-page":"e8602","DOI":"10.7759\/cureus.8602","volume":"12","author":"S Gaballa","year":"2020","unstructured":"Gaballa S, Hlaing KM, Mahler N, Moursy S, Ahmed A. A Rare Case of Immune-Mediated Primary Adrenal Insufficiency With Cytotoxic T-Lymphocyte Antigen-4 Inhibitor Ipilimumab in Metastatic Melanoma of Lung and Neck of Unknown Primary. Cureus. 2020;12(6):e8602. https:\/\/doi.org\/10.7759\/cureus.8602 . PMID: 32676241; PMCID: PMC7362642.","journal-title":"Cureus"},{"key":"10058_CR29","doi-asserted-by":"publisher","unstructured":"Rossi S, Silvetti F, Bordoni M, Ciarloni A, Salvio G, Balercia G. Pembrolizumab-induced Thyroiditis, Hypophysitis and Adrenalitis: A Case of Triple Endocrine Dysfunction. JCEM Case Rep. 2024;2(11):luae200. https:\/\/doi.org\/10.1210\/jcemcr\/luae200. Erratum in: JCEM Case Rep. 2025;3(11):luaf254. doi: 10.1210\/jcemcr\/luaf254. PMID: 39498471; PMCID: PMC11532647.","DOI":"10.1210\/jcemcr\/luae200"},{"issue":"10","key":"10058_CR30","doi-asserted-by":"publisher","first-page":"e71759","DOI":"10.7759\/cureus.71759","volume":"16","author":"\u00d6F Aydin","year":"2024","unstructured":"Aydin \u00d6F. Pembrolizumab-Induced Addison\u2019s Disease Leading to Severe Hyponatremia in a Breast Cancer Survivor: A Case Report With Implications for Emergency Department Practice. Cureus. 2024;16(10):e71759. https:\/\/doi.org\/10.7759\/cureus.71759 . PMID: 39552964; PMCID: PMC11569407.","journal-title":"Cureus"},{"issue":"11","key":"10058_CR31","doi-asserted-by":"publisher","first-page":"e231829","DOI":"10.1136\/bcr-2019-231829","volume":"12","author":"I Iqbal","year":"2019","unstructured":"Iqbal I, Khan MAA, Ullah W, Nabwani D. Nivolumab-induced adrenalitis. BMJ Case Rep. 2019;12(11):e231829. https:\/\/doi.org\/10.1136\/bcr-2019-231829 . PMID: 31791986; PMCID: PMC6887423.","journal-title":"BMJ Case Rep"},{"key":"10058_CR32","doi-asserted-by":"publisher","first-page":"526","DOI":"10.17179\/excli2018-1357","volume":"17","author":"K Aziz","year":"2018","unstructured":"Aziz K, Shahbaz A, Umair M, Sachmechi I. Avelumab inducing hypothyroidism and hypoadrenalism: A case report and review of literature. EXCLI J. 2018;17:526\u201330. https:\/\/doi.org\/10.17179\/excli2018-1357 . PMID: 30034316; PMCID: PMC6046621.","journal-title":"EXCLI J"},{"key":"10058_CR33","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvae163.255","author":"A Calderon","year":"2024","unstructured":"Calderon A, Calderon-Martinez E, Shakil J, Kansara A. 12616 Pembrolizumab-induced Autoimmune Adrenal Insufficiency: A Case Report And Literature Review. J Endocr Soc. 2024. https:\/\/doi.org\/10.1210\/jendso\/bvae163.255. 8.","journal-title":"J Endocr Soc"},{"key":"10058_CR34","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jaut.2016.03.003","volume":"69","author":"J Ji","year":"2016","unstructured":"Ji J, Sundquist J, Sundquist K. Gender-specific incidence of autoimmune diseases from national registers. J Autoimmun. 2016;69:102\u20136. https:\/\/doi.org\/10.1016\/j.jaut.2016.03.003.","journal-title":"J Autoimmun"},{"key":"10058_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2042-6410-2-1","volume":"2","author":"R Voskuhl","year":"2011","unstructured":"Voskuhl R. Sex differences in autoimmune diseases. Biology Sex Differences. 2011;2:1\u20131. https:\/\/doi.org\/10.1186\/2042-6410-2-1.","journal-title":"Biology Sex Differences"},{"key":"10058_CR36","doi-asserted-by":"publisher","first-page":"R207","DOI":"10.1530\/ec-20-0342","volume":"9","author":"M Stelmachowska-Bana\u015b","year":"2020","unstructured":"Stelmachowska-Bana\u015b M, Czajka-Oraniec I. Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review. Endocr Connections. 2020;9 R207 - R228. https:\/\/doi.org\/10.1530\/ec-20-0342","journal-title":"Endocr Connections"},{"key":"10058_CR37","doi-asserted-by":"publisher","unstructured":"Huang X, Zhang L, Zhang C, Wang H, Shao Z, Liu N, Song S, Jiang M, Hou H. Retrospective analysis of clinical characteristics and treatment of patients with immune checkpoint inhibitors-induced adrenal insufficiency. Front Oncol. 2025;15. https:\/\/doi.org\/10.3389\/fonc.2025.1614223.","DOI":"10.3389\/fonc.2025.1614223"},{"key":"10058_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2020.09.016","author":"Y Shi","year":"2020","unstructured":"Shi Y, Shen M, Zheng X, Yang T. Immune Checkpoint Inhibitor-Induced Adrenalitis and Primary Adrenal Insufficiency: Systematic Review and Optimal Management. Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2020. https:\/\/doi.org\/10.1016\/j.eprac.2020.09.016.","journal-title":"Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists"},{"key":"10058_CR39","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.4167755","author":"Q Cai","year":"2022","unstructured":"Cai Q, Wu W, Li X, Xu Q, Zhao L, Lyu Q. Immune Checkpoint Inhibitor\u2013Associated Adrenal Insufficiency in Chinese Cancer Patients: A Real-World Retrospective Analysis. SSRN Electron J. 2022. https:\/\/doi.org\/10.2139\/ssrn.4167755.","journal-title":"SSRN Electron J"},{"key":"10058_CR40","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz438.016","author":"D Etoh","year":"2019","unstructured":"Etoh D, Harada T, Shimauchi A, Ibusuki R, Kayukawa T, Okamatsu Y, Inoue K, Tsubouchi K. Incidence and characteristic of adrenal insufficiency due to immune checkpoint inhibitors therapy. Ann Oncol. 2019. https:\/\/doi.org\/10.1093\/annonc\/mdz438.016.","journal-title":"Ann Oncol"},{"issue":"1","key":"10058_CR41","doi-asserted-by":"publisher","first-page":"e191","DOI":"10.1002\/onco.13588","volume":"26","author":"C Salinas","year":"2021","unstructured":"Salinas C, Samtani S, Burotto M. Primary Adrenal Insufficiency due to Immune Checkpoint Inhibitors: More Common than We Thought. Oncologist. 2021;26(1):e191. https:\/\/doi.org\/10.1002\/onco.13588 . Epub 2020 Nov 23. PMID: 33150991; PMCID: PMC7794173.","journal-title":"Oncologist"},{"key":"10058_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2025.04.008","author":"A Surani","year":"2025","unstructured":"Surani A, Carroll T. Autoimmune Primary Adrenal Insufficiency: Understanding the Past, Present, and Future. Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2025. https:\/\/doi.org\/10.1016\/j.eprac.2025.04.008.","journal-title":"Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists"},{"key":"10058_CR43","doi-asserted-by":"publisher","unstructured":"Jennings B, Arenz A, Frankki S, Riaz A. Diagnosis and management of immune checkpoint inhibitor-associated adrenal insufficiency: A single-institution experience. J Oncol Pharm practice: official publication Int Soc Oncol Pharm Practitioners. 2025;10781552251332284. https:\/\/doi.org\/10.1177\/10781552251332284.","DOI":"10.1177\/10781552251332284"},{"key":"10058_CR44","doi-asserted-by":"publisher","unstructured":"Akmatov M, Kohring C, Pessler F, Holstiege J. Sex-specific and regional differences in the prevalence of diagnosed autoimmune diseases in Germany, 2022. Res Health Serv Reg. 2025;4. https:\/\/doi.org\/10.1007\/s43999-025-00061-5.","DOI":"10.1007\/s43999-025-00061-5"},{"key":"10058_CR45","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.yfrne.2014.04.004","volume":"35","author":"S Ngo","year":"2014","unstructured":"Ngo S, Steyn F, Mccombe P, Mccombe P. Gender differences in autoimmune disease. Front Neuroendocr. 2014;35:347\u201369. https:\/\/doi.org\/10.1016\/j.yfrne.2014.04.004.","journal-title":"Front Neuroendocr"},{"key":"10058_CR46","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jaut.2011.10.003","volume":"38","author":"O Quintero","year":"2012","unstructured":"Quintero O, Amador-Patarroyo M, Montoya-Ortiz G, Rojas-Villarraga A, Anaya J. Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J Autoimmun. 2012;38:2\u20133. https:\/\/doi.org\/10.1016\/j.jaut.2011.10.003. J109-19.","journal-title":"J Autoimmun"},{"issue":"3","key":"10058_CR47","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.ando.2023.03.014","volume":"84","author":"F Albarel","year":"2023","unstructured":"Albarel F, Brue T, Castinetti F. Pituitary and adrenal disorders induced by immune checkpoint inhibitors. Ann Endocrinol (Paris). 2023;84(3):339\u201345. https:\/\/doi.org\/10.1016\/j.ando.2023.03.014. Epub 2023 Mar 23. PMID: 36965852.","journal-title":"Ann Endocrinol (Paris)"},{"key":"10058_CR48","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2022.40.16_suppl.12092","author":"B Nguyen","year":"2022","unstructured":"Nguyen B, Shah N, Knezevic A, Newman S, Fitzgerald K, Kotecha R, Lee C, Carlo M, Aggen D, Feldman D, Shapnik N, Motzer R, Voss M, Girotra M. Long-term outcomes of adrenal insufficiency (AI) due to anti\u2013PD(L)-1 immune checkpoint inhibitors (ICI) among patients with cancer. J Clin Oncol. 2022. https:\/\/doi.org\/10.1200\/jco.2022.40.16_suppl.12092.","journal-title":"J Clin Oncol"},{"key":"10058_CR49","doi-asserted-by":"publisher","unstructured":"Husebye ES, Castinetti F, Criseno S, Curigliano G, Decallonne B, Fleseriu M, Higham CE, Lupi I, Paschou SA, Toth M, van der Kooij M, Dekkers OM. Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline. Eur J Endocrinol. 2022 Oct 25;187(6):G1\u2013G21. https:\/\/doi.org\/10.1530\/EJE-22-0689.\u00a0PMID: 36149449; PMCID: PMC9641795.","DOI":"10.1530\/EJE-22-0689"},{"key":"10058_CR50","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/s0140-6736(21)00136-7","volume":"397","author":"E Husebye","year":"2021","unstructured":"Husebye E, Pearce S, Krone N, K\u00e4mpe O. Adrenal insufficiency. Lancet. 2021;397:613\u201329. https:\/\/doi.org\/10.1016\/s0140-6736(21)00136-7.","journal-title":"Lancet"},{"key":"10058_CR51","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/eva.13167","volume":"14","author":"V Kronzer","year":"2020","unstructured":"Kronzer V, Bridges S, Davis J. Why women have more autoimmune diseases than men: An evolutionary perspective. Evol Appl. 2020;14:629\u201333. https:\/\/doi.org\/10.1111\/eva.13167.","journal-title":"Evol Appl"},{"issue":"8","key":"10058_CR52","doi-asserted-by":"publisher","first-page":"102590","DOI":"10.1016\/j.autrev.2020.102590","volume":"19","author":"P Triggianese","year":"2020","unstructured":"Triggianese P, Novelli L, Galdiero MR, Chimenti MS, Conigliaro P, Perricone R, Perricone C, Gerli R. Immune checkpoint inhibitors-induced autoimmunity: The impact of gender. Autoimmun Rev. 2020;19(8):102590. https:\/\/doi.org\/10.1016\/j.autrev.2020.102590 . Epub 2020 Jun 17. PMID: 32561463.","journal-title":"Autoimmun Rev"},{"key":"10058_CR53","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0555","author":"V Grouthier","year":"2020","unstructured":"Grouthier V, Lebrun-Vignes B, Moey M, Johnson D, Moslehi J, Salem J, Bachelot A. Immune Checkpoint Inhibitors Associated Primary Adrenal Insufficiency: WHO VigiBase Report Analysis. Oncologist. 2020. https:\/\/doi.org\/10.1634\/theoncologist.2019-0555.","journal-title":"Oncologist"},{"issue":"7","key":"10058_CR54","doi-asserted-by":"publisher","first-page":"4665","DOI":"10.3390\/curroncol29070370","volume":"29","author":"I Druce","year":"2022","unstructured":"Druce I, Tawagi K, Shaw JLV, Ibrahim A, Lochnan H, Ong M. Routine Screening for Central and Primary Adrenal Insufficiency during Immune-Checkpoint Inhibitor Therapy: An Endocrinology Perspective for Oncologists. Curr Oncol. 2022;29(7):4665\u201377. https:\/\/doi.org\/10.3390\/curroncol29070370 . PMID: 35877230; PMCID: PMC9315594.","journal-title":"Curr Oncol"},{"key":"10058_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41572-021-00252-7","volume":"7","author":"S Hahner","year":"2021","unstructured":"Hahner S, Ross R, Arlt W, Bancos I, Burger-Stritt S, Torpy D, Husebye E, Quinkler M. Adrenal insufficiency. Nat Reviews Disease Primers. 2021;7:1\u201324. https:\/\/doi.org\/10.1038\/s41572-021-00252-7.","journal-title":"Nat Reviews Disease Primers"},{"key":"10058_CR56","doi-asserted-by":"publisher","unstructured":"Helderman N, Lucas M, Blank C. Autoantibodies involved in primary and secondary adrenal insufficiency following treatment with immune checkpoint inhibitors. Immuno-Oncology Technol. 2023;17. https:\/\/doi.org\/10.1016\/j.iotech.2023.100374.","DOI":"10.1016\/j.iotech.2023.100374"},{"issue":"6","key":"10058_CR57","doi-asserted-by":"publisher","first-page":"466","DOI":"10.14341\/probl12106","volume":"65","author":"L Sozaeva","year":"2020","unstructured":"Sozaeva L, Makazan N, Nikankina L, Malysheva N, Kuvaldina E, Kareva M, Orlova E, Peterkova V. [Assessment of autoantibodies against 21-hydroxylase in the diagnosis of primary autoimmune adrenal insufficiency]. Problemy endokrinologii. 2020;65(6):466\u201373. https:\/\/doi.org\/10.14341\/probl12106.","journal-title":"Problemy endokrinologii"},{"issue":"3","key":"10058_CR58","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1210\/jcem.82.3.3849","volume":"82","author":"C Betterle","year":"1997","unstructured":"Betterle C, Volpato M, Smith R, Furmaniak J, Chen S, Zanchetta R, Greggio N, Pedini B, Boscaro M, Presotto F. II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison\u2019s disease. J Clin Endocrinol Metab. 1997;82(3):939\u201342. https:\/\/doi.org\/10.1210\/jcem.82.3.3849.","journal-title":"J Clin Endocrinol Metab"},{"key":"10058_CR59","doi-asserted-by":"publisher","unstructured":"Nuralieva N, Yukina M, Troshina E, Malysheva N, Nikankina L. Autoantibodies to 21-hydroxylase as a diagnostic marker of primary autoimmune adrenal insufficiency, including at its potential and latent stages. Almanac Clin Med. 2020;48. https:\/\/doi.org\/10.18786\/2072-0505-2020-48-023.","DOI":"10.18786\/2072-0505-2020-48-023"},{"key":"10058_CR60","doi-asserted-by":"publisher","unstructured":"Falorni A, Falorni A, Laureti S, Nikoshkov A, Picchio M, Hallengren B, Vandewalle C, Gorus F, Registry B, Tortoioli C, Luthman H, Brunetti P, Santeusanio F. 21-hydroxylase autoantibodies in adult patients with endocrine autoimmune diseases are highly specific for Addison\u2019s disease. Clin Experimental Immunol. 1997;107. https:\/\/doi.org\/10.1111\/j.1365-2249.1997.262-ce1153.x.","DOI":"10.1111\/j.1365-2249.1997.262-ce1153.x"},{"key":"10058_CR61","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1530\/eje-20-1268","volume":"184","author":"A Wolff","year":"2021","unstructured":"Wolff A, Breivik L, Hufthammer K, Grytaas M, Bratland E, Husebye E, Oftedal B. The natural history of 21-hydroxylase autoantibodies in autoimmune Addison\u2019s disease. Eur J Endocrinol. 2021;184:607\u201315. https:\/\/doi.org\/10.1530\/eje-20-1268.","journal-title":"Eur J Endocrinol"},{"issue":"9","key":"10058_CR62","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.tem.2019.06.004","volume":"30","author":"S Chiloiro","year":"2019","unstructured":"Chiloiro S, Capoluongo ED, Tartaglione T, Giampietro A, Bianchi A, Giustina A, Pontecorvi A, De Marinis L. The Changing Clinical Spectrum of Hypophysitis. Trends Endocrinol Metab. 2019;30(9):590\u2013602. https:\/\/doi.org\/10.1016\/j.tem.2019.06.004 . Epub 2019 Jul 22. PMID: 31345630.","journal-title":"Trends Endocrinol Metab"},{"issue":"4","key":"10058_CR63","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1001\/ARCHINTE.1997.00440250114013","volume":"157","author":"C Cronin","year":"1997","unstructured":"Cronin C, Callaghan N, Kearney P, Murnaghan D, Shanahan F. Addison disease in patients treated with glucocorticoid therapy. Arch Intern Med. 1997;157(4):456\u20138. https:\/\/doi.org\/10.1001\/ARCHINTE.1997.00440250114013.","journal-title":"Arch Intern Med"},{"key":"10058_CR64","doi-asserted-by":"publisher","unstructured":"Barnabei A, Senes P, Scoppola A, Chiefari A, Iannantuono G, Appetecchia M, Torino F. Endocrine toxicities of antineoplastic therapy: The adrenal topic. Cancers; 2022; 14. https:\/\/doi.org\/10.3390\/cancers14030593.","DOI":"10.3390\/cancers14030593"},{"key":"10058_CR65","doi-asserted-by":"publisher","unstructured":"Cui K, Wang Z, Zhang Q, Zhang X. Immune checkpoint inhibitors and adrenal insufficiency: a large-sample case series study. Annals Translational Med. 2021;10. https:\/\/doi.org\/10.21037\/atm-21-7006.","DOI":"10.21037\/atm-21-7006"},{"issue":"12","key":"10058_CR66","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.annonc.2022.10.001","volume":"33","author":"J Haanen","year":"2022","unstructured":"Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, Lyon AR, Wick W, Kostine M, Peters S, Jordan K, Larkin J, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(12):1217\u201338. https:\/\/doi.org\/10.1016\/j.annonc.2022.10.001 . Epub 2022 Oct 18. PMID: 36270461.","journal-title":"Ann Oncol"},{"key":"10058_CR67","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1055\/a-0843-3366","volume":"51","author":"J De Filette","year":"2018","unstructured":"De Filette J, Andreescu C, Cools F, Bravenboer B, Velkeniers B. A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors. Horm Metab Res. 2018;51:145\u201356. https:\/\/doi.org\/10.1055\/a-0843-3366.","journal-title":"Horm Metab Res"},{"key":"10058_CR68","doi-asserted-by":"publisher","unstructured":"Oprea A, Bonnet N, Poll\u00e9 O, Lysy P. Novel insights into glucocorticoid replacement therapy for pediatric and adult adrenal insufficiency. Therapeutic Adv Endocrinol Metabolism. 2019;10. https:\/\/doi.org\/10.1177\/2042018818821294.","DOI":"10.1177\/2042018818821294"},{"key":"10058_CR69","doi-asserted-by":"publisher","unstructured":"Younes N, Bourdeau I, Lacroix A. Latent adrenal insufficiency: From concept to diagnosis. Front Endocrinol. 2021;12. https:\/\/doi.org\/10.3389\/fendo.2021.720769.","DOI":"10.3389\/fendo.2021.720769"},{"key":"10058_CR70","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.semarthrit.2016.03.001","volume":"46","author":"R Joseph","year":"2016","unstructured":"Joseph R, Hunter A, Ray D, Dixon W. Systemic glucocorticoid therapy and adrenal insufficiency in adults: A systematic review. Semin Arthritis Rheum. 2016;46:133\u201341. https:\/\/doi.org\/10.1016\/j.semarthrit.2016.03.001.","journal-title":"Semin Arthritis Rheum"},{"key":"10058_CR71","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s40618-022-01889-1","volume":"46","author":"F Ceccato","year":"2022","unstructured":"Ceccato F, Torchio M, Tizianel I, Falb P, Barbot M, Sabbadin C, Betterle C, Scaroni C. Renin and electrolytes indicate the mineralocorticoid activity of fludrocortisone: a 6 year study in primary adrenal insufficiency. J Endocrinol Investig. 2022;46:111\u201322. https:\/\/doi.org\/10.1007\/s40618-022-01889-1.","journal-title":"J Endocrinol Investig"},{"key":"10058_CR72","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1210\/jc.2017-01928","volume":"103","author":"D Esposito","year":"2017","unstructured":"Esposito D, Pasquali D, Johannsson G. Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy. J Clin Endocrinol Metabolism. 2017;103:376\u201387. https:\/\/doi.org\/10.1210\/jc.2017-01928.","journal-title":"J Clin Endocrinol Metabolism"},{"issue":"1","key":"10058_CR73","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.beem.2014.08.008","volume":"29","author":"M Quinkler","year":"2015","unstructured":"Quinkler M, Oelkers W, Remde H, Allolio B. Mineralocorticoid substitution and monitoring in primary adrenal insufficiency. Best practice & research. Clin Endocrinol metabolism. 2015;29(1):17\u201324. https:\/\/doi.org\/10.1016\/j.beem.2014.08.008.","journal-title":"Clin Endocrinol metabolism"},{"issue":"2","key":"10058_CR74","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1210\/jc.2007-1134","volume":"93","author":"E Gurnell","year":"2008","unstructured":"Gurnell E, Hunt P, Curran S, Conway C, Pullenayegum E, Huppert F, Compston J, Herbert J, Chatterjee K. Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial. J Clin Endocrinol Metab. 2008;93(2):400\u20139. https:\/\/doi.org\/10.1210\/jc.2007-1134.","journal-title":"J Clin Endocrinol Metab"},{"key":"10058_CR75","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac130","author":"M Wierman","year":"2022","unstructured":"Wierman M, Vasilliades K. Should DHEA be Administered to Women? J Clin Endocrinol Metab. 2022. https:\/\/doi.org\/10.1210\/clinem\/dgac130.","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"10058_CR76","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.1210\/jc.2009-0672","volume":"94","author":"A Alkatib","year":"2009","unstructured":"Alkatib A, Cosma M, Elamin M, Erickson D, Swiglo B, Erwin P, Montori V. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab. 2009;94(10):3676\u201381. https:\/\/doi.org\/10.1210\/jc.2009-0672.","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Reviews in Endocrine and Metabolic Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11154-026-10058-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11154-026-10058-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11154-026-10058-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:16:46Z","timestamp":1780107406000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11154-026-10058-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":76,"alternative-id":["10058"],"URL":"https:\/\/doi.org\/10.1007\/s11154-026-10058-1","relation":{},"ISSN":["1389-9155","1573-2606"],"issn-type":[{"value":"1389-9155","type":"print"},{"value":"1573-2606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]},"assertion":[{"value":"11 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}