{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:25:35Z","timestamp":1792481135067,"version":"4.5.0"},"reference-count":87,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICI) prolong the survival in an increasing number of patients affected by several malignancies, but at the cost of new toxicities related to their mechanisms of action, autoimmunity. Endocrine toxicity frequently occurs in patients on ICI, but endocrine dysfunctions differ based on the ICI-subclass, as follows: agents targeting the CTLA4-receptor often induce hypophysitis and rarely thyroid dysfunction, which is the opposite for agents targeting the PD-1\/PD-L1 axis. Recently, few cases of central diabetes insipidus have been reported as an adverse event induced by both ICI-subclasses, either in the context of anterior hypophysitis or as selective damage to the posterior pituitary or in the context of hypothalamitis. These new occurrences demonstrate, for the first time, that ICI-induced autoimmunity may involve any tract of the hypothalamic\u2013pituitary axis. However, the related pathogenic mechanisms remain to be fully elucidated. Similarly, the data explaining the endocrine system susceptibility to primary and ICI-induced autoimmunity are still scarce. Since ICI clinical indications are expected to expand in the near future, ICI-induced autoimmunity to the hypothalamic\u2013pituitary axis presents as a unique in vivo model that could help to clarify the pathogenic mechanisms underlying both the dysfunction induced by ICI to the hypothalamus\u2013pituitary axis and primary autoimmune diseases affecting the same axis.<\/jats:p>","DOI":"10.3390\/cancers14041057","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:14:46Z","timestamp":1645431286000},"page":"1057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune Checkpoint Inhibitors as a Threat to the Hypothalamus\u2013Pituitary Axis: A Completed Puzzle"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0215-5853","authenticated-orcid":false,"given":"Agnese","family":"Barnabei","sequence":"first","affiliation":[{"name":"Endocrinology Unit, P.O.\u2014S. Spirito in Sassia, ASL Roma 1, Lungotevere in Sassia 1, I-00193 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Corsello","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore-Fondazione Policlinico \u201cGemelli\u201d IRCCS, Largo Gemelli 8, I-00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Paragliola","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore-Fondazione Policlinico \u201cGemelli\u201d IRCCS, Largo Gemelli 8, I-00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-6250","authenticated-orcid":false,"given":"Giovanni Maria","family":"Iannantuono","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-6826","authenticated-orcid":false,"given":"Luca","family":"Falzone","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, IRCCS Istituto Nazionale Tumori \u2018Fondazione G. Pascale\u2019, I-80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore Maria","family":"Corsello","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore-Fondazione Policlinico \u201cGemelli\u201d IRCCS, Largo Gemelli 8, I-00168 Rome, Italy"},{"name":"UniCamillus, Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro, 8, I-00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-4438","authenticated-orcid":false,"given":"Francesco","family":"Torino","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"252","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":"ref_2","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","article-title":"Fundamental Mechanisms of Immune Checkpoint Blockade Therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-Related Adverse Events Associated with Immune Checkpoint Blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sullivan, R.J., and Weber, J.S. (2021). Immune-Related Toxicities of Checkpoint Inhibitors: Mechanisms and Mitigation Strategies. Nat. Rev. Drug Discov.","DOI":"10.1038\/s41573-021-00259-5"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Deshpande, R.P., Sharma, S., and Watabe, K. (2020). The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors. Cancers, 12.","DOI":"10.3390\/cancers12102983"},{"key":"ref_6","doi-asserted-by":"crossref","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":"ref_7","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":"Barry","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1055\/a-0843-3366","article-title":"A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors","volume":"51","author":"Andreescu","year":"2019","journal-title":"Horm. Metab. Res."},{"key":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","first-page":"1077","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. Cancer Netw."},{"key":"ref_11","first-page":"17","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":"ref_12","doi-asserted-by":"crossref","first-page":"365","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":"ref_13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ejca.2018.09.016","article-title":"Hypothalamitis and Severe Hypothalamic Dysfunction Associated with Anti-Programmed Cell Death Ligand 1 Antibody Treatment","volume":"104","author":"Tshuma","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106427","DOI":"10.1016\/j.intimp.2020.106427","article-title":"Central Diabetes Insipidus Related to Anti-Programmed Cell-Death 1 Protein Active Immunotherapy","volume":"83","author":"Deligiorgi","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"582394","DOI":"10.3389\/fonc.2020.582394","article-title":"Case Report: Ipilimumab-Induced Panhypophysitis: An Infrequent Occurrence and Literature Review","volume":"10","author":"Barnabei","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/01.ccm.0000619648.08126.8f","article-title":"Diabetes insipidus in checkpoint inhibitor treatment and acute myeloid leukemia","volume":"48","author":"Grami","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_17","first-page":"483","article-title":"Permanent Diabetes Insipidus in a Patient with Mesothelioma Treated with Immunotherapy","volume":"64","author":"Brilli","year":"2020","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.2217\/imt-2020-0334","article-title":"Anti-PD-1 Treatment-Induced Immediate Central Diabetes Insipidus: A Case Report","volume":"13","author":"Yu","year":"2021","journal-title":"Immunotherapy"},{"key":"ref_19","first-page":"EDM200123","article-title":"Diabetes Insipidus Secondary to Nivolumab-Induced Neurohypophysitis and Pituitary Metastasis","volume":"2021","author":"Fosci","year":"2021","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_20","unstructured":"Melmed, S., Polonsky, K., Larsen, P.R., and Kronenberg, H.M. (2015). Posterior Pituitary. Williams Textbook of Endocrinology, Elsevier. [13th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/nrendo.2016.193","article-title":"An Updated View of Hypothalamic-Vascular-Pituitary Unit Function and Plasticity","volume":"13","author":"Campos","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e415","DOI":"10.1210\/clinem\/dgaa771","article-title":"Hypothalamitis: A Novel Autoimmune Endocrine Disease. A Literature Review and Case Report","volume":"106","author":"Harput","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1530\/EJE-07-0156","article-title":"Hypothalamic and Pituitary Development: Novel Insights into the Aetiology","volume":"157","author":"Kelberman","year":"2007","journal-title":"Eur. J. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11154-005-3047-7","article-title":"Early Development of the Pituitary Gland: Induction and Shaping of Rathke\u2019s Pouch","volume":"6","author":"Rizzoti","year":"2005","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_25","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dhatariya, K., Dungan, K., Hershman, J.M., Hofland, J., and Kalra, S. (2000). Hypophysitis. Endotext (Internet), MDText.com, Inc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40842-016-0034-8","article-title":"Hypophysitis: Evaluation and Management","volume":"2","author":"Faje","year":"2016","journal-title":"Clin. Diabetes Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1210\/er.2004-0011","article-title":"Autoimmune Hypophysitis","volume":"26","author":"Caturegli","year":"2005","journal-title":"Endocr. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","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":"Cordes","year":"2020","journal-title":"Oncologist"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/17446651.2019.1701434","article-title":"Hypophysitis Induced by Immune Checkpoint Inhibitors: A 10-Year Assessment","volume":"14","author":"Ippolito","year":"2019","journal-title":"Expert. Rev. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","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":"ref_31","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.eprac.2020.09.016","article-title":"Immune Checkpoint Inhibitor-Induced Adrenalitis and Primary Adrenal Insufficiency: Systematic Review and Optimal Management","volume":"27","author":"Shi","year":"2021","journal-title":"Endocr. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/cen.13866","article-title":"Diagnosis and Management of Central Diabetes Insipidus in Adults","volume":"90","author":"Garrahy","year":"2019","journal-title":"Clin. Endocrinol"},{"key":"ref_33","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dhatariya, K., Dungan, K., Hershman, J.M., Hofland, J., and Kalra, S. (2000). Diabetes Insipidus. Endotext (Internet), MDText.com, Inc."},{"key":"ref_34","unstructured":"(2021, October 21). Clinical Manifestations and Causes of Central Diabetes Insipidus. Available online: www.uptodate.com."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/B978-0-12-820683-6.00015-4","article-title":"Autoimmune diabetes insipidus","volume":"181","author":"Scherbaum","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1210\/jcem.84.9.5945","article-title":"A Longitudinal Study of Vasopressin Cell Antibodies, Posterior Pituitary Function, and Magnetic Resonance Imaging Evaluations in Subclinical Autoimmune Central Diabetes Insipidus","volume":"84","author":"Colao","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1210\/jc.2013-2435","article-title":"Central Diabetes Insipidus: A Previously Unreported Side Effect of Temozolomide","volume":"98","author":"Faje","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1177\/1078155220961551","article-title":"Central Diabetes Insipidus Induced by Temozolomide: A Report of Two Cases","volume":"27","author":"Mahiat","year":"2021","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e28516","DOI":"10.1002\/pbc.28516","article-title":"Central Diabetes Insipidus: A Rare Unreported Side Effect of Temozolomide in Pediatrics","volume":"67","author":"Kuo","year":"2020","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_40","unstructured":"(2021, October 21). Diagnostic Testing for Diabetes Insipidus. Available online: www.endotext.org."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"222","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":"ref_42","unstructured":"(2021, October 20). Treatment of Central Diabetes Insipidus. Available online: www.uptodate.com."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00228-004-0781-9","article-title":"Pharmacokinetics and Pharmacodynamics of Desmopressin Administered Orally versus Intravenously at Daytime versus Night-Time in Healthy Men Aged 55\u201370 Years","volume":"60","author":"Rembratt","year":"2004","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1210\/jc.2013-2326","article-title":"Clinical Review: Treatment of Neurohypophyseal Diabetes Insipidus","volume":"98","author":"Oiso","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1507\/endocrj.EJ13-0165","article-title":"Efficacy and Safety of Desmopressin Orally Disintegrating Tablet in Patients with Central Diabetes Insipidus: Results of a Multicenter Open-Label Dose-Titration Study","volume":"60","author":"Arima","year":"2013","journal-title":"Endocr. J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wass, J., Stewart, P.M., Amiel, S.A., and Davies, M.J. (2011). Hypothalamic dysfunction (hypothalamic syndromes). Oxford Textbook of Endocrinology and Diabetes, Oxford University Press. [2nd ed.].","DOI":"10.1093\/med\/9780199235292.001.1"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/B978-0-12-820683-6.00011-7","article-title":"Hypothalamitis and Pituitary Atrophy","volume":"181","author":"Chiloiro","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11102-013-0487-z","article-title":"Hypothalamitis: A Diagnostic and Therapeutic Challenge","volume":"17","author":"Bianchi","year":"2014","journal-title":"Pituitary"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1600-0404.2012.01691.x","article-title":"The Diagnosis and Treatment of Limbic Encephalitis","volume":"126","author":"Asztely","year":"2012","journal-title":"Acta Neurol. Scand."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bataduwaarachchi, V.R., and Tissera, N. (2016). Paraneoplastic Limbic Encephalitis with Associated Hypothalamitis Mimicking a Hyperdense Hypothalamic Tumor: A Case Report. BMC Med. Imaging, 16.","DOI":"10.1186\/s12880-016-0113-4"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/RCT.0000000000000504","article-title":"Magnetic Resonance Imaging Features of Solitary Hypothalamitis","volume":"41","author":"Zhang","year":"2017","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"300060519887832","DOI":"10.1177\/0300060519887832","article-title":"Clinical Aspects of Autoimmune Hypothalamitis, a Variant of Autoimmune Hypophysitis: Experience from One Center","volume":"48","author":"Wei","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1473","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. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1210\/edrv.19.2.0328","article-title":"The Endocrine Effects of Nonhormonal Antineoplastic Therapy","volume":"19","author":"Yeung","year":"1998","journal-title":"Endocr. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/jnci\/djr373","article-title":"Thyroid Dysfunction from Antineoplastic Agents","volume":"103","author":"Hamnvik","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrclinonc.2009.4","article-title":"Hypothyroidism Related to Tyrosine Kinase Inhibitors: An Emerging Toxic Effect of Targeted Therapy","volume":"6","author":"Torino","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"186","DOI":"10.2174\/1389200218666170105165832","article-title":"Toxicities of Receptor Tyrosine Kinase Inhibitors in Cancer Pharmacotherapy: Management with Clinical Pharmacology","volume":"18","author":"Fujita","year":"2017","journal-title":"Curr. Drug. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.critrevonc.2013.07.007","article-title":"Chemotherapy-Induced Ovarian Toxicity in Patients Affected by Endocrine-Responsive Early Breast Cancer","volume":"89","author":"Torino","year":"2014","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1200\/JCO.2002.03.052","article-title":"Mechanisms and Management of Toxicities Associated with High-Dose Interferon Alfa-2b Therapy","volume":"20","author":"Kirkwood","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","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":"ref_61","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/pin.13161","article-title":"An Autopsy Case Study of Lymphocytic Hypophysitis Induced by Nivolumab Treatment for Esophageal Malignant Melanoma","volume":"71","author":"Okabe","year":"2021","journal-title":"Pathol. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"520","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":"ref_63","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.4049\/jimmunol.2001073","article-title":"Th17 Cells Contribute to the Pathology of Autoimmune Hypophysitis","volume":"206","author":"Chalan","year":"2021","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejca.2020.10.006","article-title":"Evidence for Interleukin 17 Involvement in Severe Immune-Related Neuroendocrine Toxicity","volume":"141","author":"Mazzarella","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3445","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":"ref_66","doi-asserted-by":"crossref","first-page":"506","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":"ref_67","doi-asserted-by":"crossref","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":"ref_68","doi-asserted-by":"crossref","first-page":"3225","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":"ref_69","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1210\/jc.2012-2269","article-title":"Involvement of Hypothalamus Autoimmunity in Patients with Autoimmune Hypopituitarism: Role of Antibodies to Hypothalamic Cells","volume":"97","author":"Sinisi","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bellastella, G., Maiorino, M.I., Longo, M., Cirillo, P., Scappaticcio, L., Vietri, M.T., Bellastella, A., Esposito, K., and De Bellis, A. (2020). Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041392"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1530\/eje.0.1490363","article-title":"Lymphocytic Hypophysitis: A Rare or Underestimated Disease?","volume":"149","author":"Bellastella","year":"2003","journal-title":"Eur. J. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.autrev.2008.04.016","article-title":"Pituitary Autoimmunity: 30 Years Later","volume":"7","author":"Caturegli","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"ref_73","first-page":"EDM190102","article-title":"Clinical Heterogeneity of Hypophysitis Secondary to PD-1\/PD-L1 Blockade: Insights from Four Cases","volume":"2019","author":"Lupi","year":"2019","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bellastella, G., Carbone, C., Scappaticcio, L., Cirillo, P., Troiani, T., Morgillo, F., Vietri, M.T., Della Corte, C.M., De Falco, V., and Napolitano, S. (2021). Hypothalamic-Pituitary Autoimmunity in Patients Treated with Anti-PD-1 and Anti-PD-L1 Antibodies. Cancers, 13.","DOI":"10.3390\/cancers13164036"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41423-019-0232-2","article-title":"Hypothalamic Expression of PD-L1: Does It Mediate Hypothalamitis?","volume":"16","author":"Iervasi","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1136\/jnnp-2020-323212","article-title":"Encephalitis as an Immune-Related Adverse Event","volume":"91","author":"Suzuki","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EC-18-0068","article-title":"Society for Endocrinology Endocrine Emergency Guidance: Acute Management of the Endocrine Complications of Checkpoint Inhibitor Therapy","volume":"7","author":"Higham","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"iv119","DOI":"10.1093\/annonc\/mdx225","article-title":"Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"28","author":"Haanen","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1714","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":"ref_80","doi-asserted-by":"crossref","first-page":"e002435","DOI":"10.1136\/jitc-2021-002435","article-title":"Society for Immunotherapy of Cancer (SITC) Clinical Practice Guideline on Immune Checkpoint Inhibitor-Related Adverse Events","volume":"9","author":"Brahmer","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_81","unstructured":"(2021, October 21). NCCN Guidelines\u00ae for Management of Immunotherapy-Related Toxicities in NCCN Guidelines for Supportive Care. Version 2. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/immunotherapy.pdf."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1002\/cncr.31629","article-title":"High-Dose Glucocorticoids for the Treatment of Ipilimumab-Induced Hypophysitis Is Associated with Reduced Survival in Patients with Melanoma","volume":"124","author":"Faje","year":"2018","journal-title":"Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e000779","DOI":"10.1136\/jitc-2020-000779","article-title":"Pituitary Dysfunction Induced by Immune Checkpoint Inhibitors Is Associated with Better Overall Survival in Both Malignant Melanoma and Non-Small Cell Lung Carcinoma: A Prospective Study","volume":"8","author":"Kobayashi","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/annonc\/mdw640","article-title":"Antibody-Mediated Thyroid Dysfunction during T-Cell Checkpoint Blockade in Patients with Non-Small-Cell Lung Cancer","volume":"28","author":"Osorio","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Yamauchi, I., Yasoda, A., Matsumoto, S., Sakamori, Y., Kim, Y.H., Nomura, M., Otsuka, A., Yamasaki, T., Saito, R., and Kitamura, M. (2019). Incidence, Features, and Prognosis of Immune-Related Adverse Events Involving the Thyroid Gland Induced by Nivolumab. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216954"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3803\/EnM.2021.1007","article-title":"Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors","volume":"36","author":"Iwama","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/MED.0000000000000664","article-title":"Survival Benefit of Endocrine Dysfunction Following Immune Checkpoint Inhibitors for Nonthyroidal Cancers","volume":"28","author":"Kotwal","year":"2021","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/1057\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:22:54Z","timestamp":1760134974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/1057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":87,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14041057"],"URL":"https:\/\/doi.org\/10.3390\/cancers14041057","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]}}}