{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:45Z","timestamp":1760146365853,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Immunotherapy is one of the greatest advancements in oncological patient care. The broader the treatment application, the more common the adverse events associated with the therapy. Immune checkpoint inhibitors (ICI) are currently used in numerous malignancies. These drugs influence the immune cells\u2019 interactions, which translates to interruption of immune evasion and increased anti-tumor activity. However, the disruption of immunological signaling pathways often leads to adverse events, such as endocrinological insufficiencies, among which thyroid is the most common. Moreover, the co-appearance of several insufficiencies has been previously described. Case report: A 73-year-old female treated with durvalumab due to non-small cell lung carcinoma was admitted to the emergency unit due to symptoms of ketoacidosis. She had a history of well-controlled type 2 diabetes mellitus and autoimmune thyroiditis. Laboratory results showed increased anti-GAD antibodies, while the low C-peptide level indicated type 1 diabetes mellitus. Moreover, over the course of longer observation, the patient presented with abrupt aggravation of her autoimmune thyroiditis. Conclusions: The new onset of endocrinological insufficiencies is a rare adverse event of immunotherapy. Clinicians must pay particular attention to any signs indicating these life-threatening conditions. In case of the appearance of any endocrinological adverse event, the close cooperation of oncologists and endocrinologists is required to enhance patients\u2019 quality of life.<\/jats:p>","DOI":"10.3390\/jcm13216322","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T04:28:43Z","timestamp":1729657723000},"page":"6322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Double-Edged Sword of Immunotherapy\u2014Durvalumab-Induced Polyendocrinopathy\u2014Case Report"],"prefix":"10.3390","volume":"13","author":[{"given":"Olga","family":"B\u0142a\u017cowska","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7614-1108","authenticated-orcid":false,"given":"Katarzyna","family":"Str\u00f3\u017cna","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1596-2232","authenticated-orcid":false,"given":"Hanna","family":"Dancewicz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1404-7544","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Zygmunciak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Zgliczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Centre of Postgraduate Medical Education, Marymoncka St. 99\/103, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1160-9204","authenticated-orcid":false,"given":"Beata","family":"Mrozikiewicz-Rakowska","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Centre of Postgraduate Medical Education, Marymoncka St. 99\/103, 01-813 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1053\/j.seminoncol.2015.02.007","article-title":"PD-L1 Blockade for Cancer Treatment: MEDI4736","volume":"42","author":"Ibrahim","year":"2015","journal-title":"Semin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1158\/2326-6066.CIR-14-0191","article-title":"Identification and Characterization of MEDI4736, an Antagonistic Anti\u2013PD-L1 Monoclonal Antibody","volume":"3","author":"Stewart","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1056\/NEJMoa1809697","article-title":"Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC","volume":"379","author":"Antonia","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1200\/JCO.2023.41.16_suppl.2509","article-title":"Clinical and immune phenotypes associated with immune checkpoint inhibitor-induced autoimmune diabetes","volume":"41","author":"Shank","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41392-023-01522-4","article-title":"Immune checkpoint therapy for solid tumours: Clinical dilemmas and future trends","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yin, Q., Wu, L., Han, L., Zheng, X., Tong, R., Li, L., Bai, L., and Bian, Y. (2023). Immune-related adverse events of immune checkpoint inhibitors: A review. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1167975"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1158\/2326-6066.CIR-18-0245","article-title":"Autoantibody Development under Treatment with Immune-Checkpoint Inhibitors","volume":"7","author":"Rozeman","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1530\/ERC-13-0499","article-title":"Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: A comprehensive retrospective review from a single institution","volume":"21","author":"Ryder","year":"2014","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.2217\/fon-2020-1222","article-title":"Immune-Related Adverse Events with PD-1 Versus PD-L1 Inhibitors: A Meta-Analysis of 8730 Patients from Clinical Trials","volume":"17","author":"Sonpavde","year":"2021","journal-title":"Futur. Oncol."},{"key":"ref_12","unstructured":"(2024, October 20). Nivolumab Label Information 2018. Available online: https:\/\/packageinserts.bms.com\/pi\/pi_opdivo.pdf."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1158\/1078-0432.CCR-19-2609","article-title":"First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and\/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies","volume":"26","author":"Papadopoulos","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S845","DOI":"10.1016\/j.annonc.2021.08.1375","article-title":"991P Treatment-related adverse events (TRAEs) occurring during dostarlimab therapy in the GARNET study","volume":"32","author":"Berton","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1056\/NEJMoa2216334","article-title":"Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer","volume":"388","author":"Mirza","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_17","first-page":"19","article-title":"Simultaneous onset of type 1 diabetes mellitus and silent thyroiditis under durvalumab treatment","volume":"2019","author":"Capel","year":"2019","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_18","first-page":"19","article-title":"Durvalumab-induced diabetic ketoacidosis followed by hypothyroidism","volume":"2019","author":"Patel","year":"2019","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8295","DOI":"10.1038\/s41598-018-26471-9","article-title":"Interferon-gamma drives programmed death-ligand 1 expression on islet \u03b2 cells to limit T cell function during autoimmune diabetes","volume":"8","author":"Osum","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"22584","DOI":"10.3390\/ijms160922584","article-title":"Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus","volume":"16","author":"Perri","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fujiwara, M., Shimizu, M., Okano, T., Maejima, Y., and Shimomura, K. (2023). Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: A case report and systematic review. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1264056"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s00592-019-01402-w","article-title":"The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors","volume":"56","author":"Marchand","year":"2019","journal-title":"Acta Diabetol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.6004\/jnccn.2019.0013","article-title":"Management of immunotherapy-related toxicities","volume":"17","author":"Thompson","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/cncr.31200","article-title":"Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management","volume":"124","author":"Ott","year":"2018","journal-title":"Cancer"},{"key":"ref_25","first-page":"560","article-title":"Immune checkpoint inhibitors in clinical practice: Update on management of immune-related toxicities","volume":"4","author":"Villadolid","year":"2015","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"bcr2016217454","DOI":"10.1136\/bcr-2016-217454","article-title":"Glucocorticoids did not reverse type 1 diabetes mellitus secondary to pembrolizumab in a patient with metastatic melanoma","volume":"2016","author":"Aleksova","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"568","DOI":"10.5603\/EP.2017.0060","article-title":"Glucocorticoids and beta-cell function","volume":"68","author":"Fichna","year":"2017","journal-title":"Endokrynol. Pol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.4239\/wjd.v6.i8.1073","article-title":"Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review","volume":"6","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_29","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":"2018","journal-title":"Endocr. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1177\/0897190019850929","article-title":"Programmed Cell Death-1 Monoclonal Antibody Therapy and Type 1 Diabetes Mellitus: A Review of the Literature","volume":"34","author":"Farina","year":"2021","journal-title":"J. Pharm. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3747\/co.25.4235","article-title":"Immune-Related Adverse Events of Immune Checkpoint Inhibitors: A Brief Review","volume":"25","author":"Myers","year":"2018","journal-title":"Curr. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11912-020-0897-9","article-title":"Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls","volume":"22","author":"Darnell","year":"2020","journal-title":"Curr. Oncol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.annonc.2022.10.001","article-title":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Haanen","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2337\/dbi18-0002","article-title":"Collateral Damage: Insulin-Dependent Diabetes Induced with Checkpoint Inhibitors","volume":"67","author":"Stamatouli","year":"2018","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1530\/EJE-19-0291","article-title":"Immune checkpoint inhibitors and type 1 diabetes mellitus: A case report and systematic review","volume":"181","author":"Pen","year":"2019","journal-title":"Eur. J. Endocrinol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/21\/6322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:18:16Z","timestamp":1760113096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/21\/6322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,23]]},"references-count":35,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["jcm13216322"],"URL":"https:\/\/doi.org\/10.3390\/jcm13216322","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,10,23]]}}}