{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:38:07Z","timestamp":1787647087849,"version":"build-2736575974"},"reference-count":15,"publisher":"Endocrinology Research Centre","issue":"2","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>The exponential rise in the use of immune checkpoint inhibitors (Ipilimumab, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, and Avelumab) as the new standard for cancer treatment increase the incidence the immune-related adverse events due to immune activation. Endocrine immune-related adverse events are the third most commonly reported. Thyroid gland is most susceptible to autoimmune dysfunctions from immune checkpoint inhibitors and associated with the use of anti-PD-1 monoclonal antibodies. Hypophysitis develops more often during therapy with anti-CTLA-4 monoclonal antibodies. But such immune-related adverse events as diabetes mellitus, hypoparathyroidism are rare (about 1% of cases).We present a clinical case of the patient with skin melanoma who was prescribed therapy with immune checkpoints inhibitors (Pembrolizumab). Immune-related adverse events developed with damage to the endocrine organs after 3 Pembrolizumab injections. Of greatest interest is the development of two endocrine immune-related adverse events at once: destructive thyroiditis (with a short phase of thyrotoxicosis and subsequent persistent hypothyroidism) and diabetes mellitus. We tried to reflect the chronology of diseases and their features as fully as possible for endocrinologists, oncologists, therapists, family doctors and other medical doctors of related specialties.<\/jats:p>","DOI":"10.14341\/probl12698","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T19:53:11Z","timestamp":1621367591000},"page":"20-27","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":3,"title":["Development of destructive thyroiditis and diabetes mellitus after three injections of pembrolizumab for skin melanoma"],"prefix":"10.14341","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7324-8344","authenticated-orcid":true,"given":"A. A.","family":"Glibka","sequence":"first","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-7877","authenticated-orcid":true,"given":"G. A.","family":"Mel`nichenko","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4382-0514","authenticated-orcid":true,"given":"M. S.","family":"Mikhina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-9381","authenticated-orcid":true,"given":"N. V.","family":"Mazurina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5487-2299","authenticated-orcid":true,"given":"G. Yu.","family":"Kharkevich","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5458","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"ref1","unstructured":"NobelPrize.org. [Internet]. The Nobel Prize in Physiology or Medicine 2018. [cited 2020 Nov 30]. Available from: https:\/\/www.nobelprize.org\/prizes\/medicine\/2018\/summary\/"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Shubnikova EV, Bukatina TM, Velts NYu, et al. Immune checkpoint inhibitors: new risks of a new class of antitumour agents. Safety and Risk of Pharmacotherapy. 2020;8(1):9-22. (In Russ.) doi: https: doi.org\/10.30895\/2312-7821-2020-8-1-9-22","DOI":"10.30895\/2312-7821-2020-8-1-9-22"},{"key":"ref3","unstructured":"Grls.rosminzdrav.ru. [Internet]. [cited 2020 Nov 30]. Available from: https:\/\/grls.rosminzdrav.ru\/grls.aspx."},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Mazarico I, Capel I, Gim\u00e9nez-Palop O, et al. 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(In Russ.) doi: https:\/\/doi.org\/10.14341\/omet9834","DOI":"10.14341\/omet9834"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Standards of specialized diabetes care. Ed. by Dedov II, Shestakova MV, Mayorov AYu. 9th Edition (revised). Moscow; 2019. (In Russ.) doi: https:\/\/doi.org\/10.14341\/DM221S1","DOI":"10.14341\/DM221S1"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Nardin C, Jeand\u2019heur A, Bouiller K, et al. Vitiligo under anti-programmed cell death-1 therapy is associated with increased survival in melanoma patients. J Am Acad Dermatol. 2020;82(3):770-772. doi: https:\/\/doi.org\/10.1016\/j.jaad.2019.11.017","DOI":"10.1016\/j.jaad.2019.11.017"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Gracia-Caza\u00f1a T, Padgett E, Hern\u00e1ndez-Garc\u00eda A, et al. Vitiligo-like lesions located over In-transit metastases of malignant melanoma as a clinical marker of complete response to pembrolizumab. Dermatol Online J. 2019;25(12):12.","DOI":"10.5070\/D32512046728"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Hakami OA, Ioana J, Ahmad S, et al. A case of pembrolizumabinduced severe DKA and hypothyroidism in a patient with metastatic melanoma. Endocrinol Diabetes Metab Case Reports. 2019;2019. doi: https:\/\/doi.org\/10.1530\/EDM-18-0153","DOI":"10.1530\/EDM-18-0153"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Barroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 20181;4(2):173-182. doi: https:\/\/doi.org\/10.1001\/jamaoncol.2017.3064","DOI":"10.1001\/jamaoncol.2017.3064"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Gunawan F, George E, Roberts A. Combination immune checkpoint inhibitor therapy nivolumab and ipilimumab associated with multiple endocrinopathies. Endocrinol Diabetes Metab Case Rep. 2018;17-0146. doi: https:\/\/doi.org\/10.1530\/EDM-17-0146.","DOI":"10.1530\/EDM-17-0146"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/12698\/9917","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T20:41:44Z","timestamp":1672173704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/12698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":15,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,5,18]]}},"URL":"https:\/\/doi.org\/10.14341\/probl12698","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"value":"2308-1430","type":"electronic"},{"value":"0375-9660","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5,18]]}}}