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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Almanac of Clinical Medicine</journal-id><journal-title-group><journal-title xml:lang="en">Almanac of Clinical Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Альманах клинической медицины</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2072-0505</issn><issn publication-format="electronic">2587-9294</issn><publisher><publisher-name xml:lang="en">Moscow Regional Research and Clinical Institute (MONIKI)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1767</article-id><article-id pub-id-type="doi">10.18786/2072-0505-2022-50-056</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>CLINICAL CASES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Development of three endocrinopathies under nivolumab therapy</article-title><trans-title-group xml:lang="ru"><trans-title>Развитие трех эндокринопатий на фоне терапии ниволумабом</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7324-8344</contrib-id><name-alternatives><name xml:lang="en"><surname>Glibka</surname><given-names>Anastasia A.</given-names></name><name xml:lang="ru"><surname>Глибка</surname><given-names>Анастасия Андреевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Endocrinologist</p></bio><bio xml:lang="ru"><p>врач-эндокринолог</p></bio><email>anastasiya_glibka@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8077-9381</contrib-id><name-alternatives><name xml:lang="en"><surname>Mazurina</surname><given-names>Natalya V.</given-names></name><name xml:lang="ru"><surname>Мазурина</surname><given-names>Наталия Валентиновна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Leading Research Fellow, Department of Therapeutic Endocrinology</p></bio><bio xml:lang="ru"><p>д-р мед. наук, вед. науч. сотр. отдела терапевтической эндокринологии</p></bio><email>natalyamazurina@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1679-7985</contrib-id><name-alternatives><name xml:lang="en"><surname>Gridnev</surname><given-names>Danila I.</given-names></name><name xml:lang="ru"><surname>Гриднев</surname><given-names>Данила Игоревич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Oncologist, Department of Oncology No. 8 (Chemotherapy), Oncological In-Patient Unit</p></bio><bio xml:lang="ru"><p>врач-онколог онкологического отделения № 8 (химиотерапия) онкологического стационара</p></bio><email>danya.darko@yandex.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7817-8429</contrib-id><name-alternatives><name xml:lang="en"><surname>Sarantseva</surname><given-names>Ksenia A.</given-names></name><name xml:lang="ru"><surname>Саранцева</surname><given-names>Ксения Андреевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Research Fellow, Department of Medicinal Methods of Treatment No. 173</p></bio><bio xml:lang="ru"><p>канд. мед. наук, науч. сотр. отделения лекарственных методов лечения № 173</p></bio><email>sarantsevaka@gmail.com</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8520-8702</contrib-id><name-alternatives><name xml:lang="en"><surname>Troshina</surname><given-names>Ekaterina A.</given-names></name><name xml:lang="ru"><surname>Трошина</surname><given-names>Екатерина Анатольевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Professor, Corr. Member of Russ. Acad. Sci., Director of Institute of Clinical Endocrinology, Deputy Director</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор, чл.-корр. РАН, директор Института клинической эндокринологии, заместитель директора</p></bio><email>troshina@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Endocrinology Research Centre</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Сity Clinical Hospital named after D.D. Pletnev</institution></aff><aff><institution xml:lang="ru">ГБУЗ г. Москвы «Городская клиническая больница им. Д.Д. Плетнева ДЗМ»</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">N.N. Blokhin National Medical Research Center of Oncology</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2022-12-23" publication-format="electronic"><day>23</day><month>12</month><year>2022</year></pub-date><volume>50</volume><issue>8</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>490</fpage><lpage>496</lpage><history><date date-type="received" iso-8601-date="2022-11-26"><day>26</day><month>11</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2023-01-09"><day>09</day><month>01</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2022, Glibka A.A., Mazurina N.V., Gridnev D.I., Sarantseva K.A., Troshina E.A.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2022, Глибка А.А., Мазурина Н.В., Гриднев Д.И., Саранцева К.А., Трошина Е.А.</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="en">Glibka A.A., Mazurina N.V., Gridnev D.I., Sarantseva K.A., Troshina E.A.</copyright-holder><copyright-holder xml:lang="ru">Глибка А.А., Мазурина Н.В., Гриднев Д.И., Саранцева К.А., Трошина Е.А.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://almclinmed.ru/jour/article/view/1767">https://almclinmed.ru/jour/article/view/1767</self-uri><abstract xml:lang="en"><p>Active implementation of immune checkpoint inhibitors into oncology practice leads to an increase in numbers of observed immune-mediated adverse events, including various endocrinopathies. The focus is on multiple endocrine gland involvement because their predictors are unclear.</p> <p>The paper describes a clinical case of a patient with central cancer of the right lung, who had been administered immune therapy with anti-PD-1 monoclonal antibody (nivolumab). Under this treatment, three endocrine immune-mediated adverse events developed without any concomitant problems from other organs and body systems. The most interesting was the occurrence of adrenal insufficiency and fulminant diabetes mellitus, while, unlike hypothyroidism, which also developed in this patient, those two have been significantly less often described and up to now their incidence, prevalence and association with a certain subgroup of immune checkpoint inhibitors have not been identified. Despite multiple endocrine organ involvement and taking into account positive effects of the anti-tumor treatment, as well as titration of the corresponding hormonal replacement therapy, treatment with nivolumab was continued.</p> <p>Patients treated with immune checkpoint inhibitors require a multidisciplinary team approach including an endocrinologist, because of the potential multiple endocrinopathies, including life-threatening.</p></abstract><trans-abstract xml:lang="ru"><p>Активное применение ингибиторов контрольных точек иммунного ответа в онкологической практике приводит к увеличению числа наблюдаемых иммуноопосредованных нежелательных явлений, в том числе различных эндокринопатий. В фокусе внимания случаи с развитием полигландулярных поражений по причине их неясных предикторов.</p> <p>В статье приведено клиническое наблюдение пациента с центральным раком правого легкого, которому была назначена иммунотерапия анти-PD-1-моноклональным антителом (ниволумаб). На фоне данной терапии развилось три эндокринных иммуноопосредованных нежелательных явления без сопутствующего поражения других органов и систем. Наибольший интерес представляет возникновение надпочечниковой недостаточности и фульминантного сахарного диабета, так как в отличие от гипотиреоза, также развившегося у пациента, они описываются значимо реже и на данный момент не определена частота их встречаемости и ассоциация с определенной подгруппой препаратов ингибиторов контрольных точек. Невзирая на множественное поражение органов эндокринной системы, с учетом наличия положительной динамики в противоопухолевом лечении и подбора соответствующей гормональной терапии лечение ниволумабом было продолжено.</p> <p>Пациенты, получающие ингибиторы контрольных точек, нуждаются в мультидисциплинарном ведении с участием эндокринолога, так как существует вероятность развития множественных (в том числе жизнеугрожающих) эндокринопатий.</p></trans-abstract><kwd-group xml:lang="en"><kwd>immune checkpoint inhibitors</kwd><kwd>nivolumab</kwd><kwd>endocrine immune-mediated adverse events</kwd><kwd>adrenal insufficiency</kwd><kwd>hypothyroidism</kwd><kwd>diabetes mellitus</kwd><kwd>lung cancer</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>ингибиторы контрольных точек</kwd><kwd>ниволумаб</kwd><kwd>эндокринные иммуноопосредованные нежелательные явления</kwd><kwd>надпочечниковая недостаточность</kwd><kwd>гипотиреоз</kwd><kwd>сахарный диабет</kwd><kwd>рак легкого</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Правительство РФ</institution></institution-wrap></funding-source><award-id>Рег. №АААА-А20-120011790180-4</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Vaddepally RK, Kharel P, Pandey R, Garje R, Chandra AB. Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence. Cancers (Basel). 2020;12(3):738. doi: 10.3390/cancers12030738.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Khader A, Bokhari R, Hakimelahi R, Scheirey C, Afnan J, Braschi-Amirfarzan M, Thomas R. A radiologist's guide to novel anticancer therapies in the era of precision medicine. Eur J Radiol Open. 2022;9:100406. doi: 10.1016/j.ejro.2022.100406.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Liu X, Hogg GD, DeNardo DG. Rethinking immune checkpoint blockade: 'Beyond the T cell'. J Immunother Cancer. 2021;9(1):e001460. doi: 10.1136/jitc-2020-001460.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>de Filette J, Andreescu CE, 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. 2019;51(3):145–156. doi: 10.1055/a-0843-3366.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Mazarico I, Capel I, Giménez-Palop O, Albert L, Berges I, Luchtenberg F, García Y, Fernández-Morales LA, De Pedro VJ, Caixàs A, Rigla M. Low frequency of positive antithyroid antibodies is observed in patients with thyroid dysfunction related to immune check point inhibitors. J Endocrinol Invest. 2019;42(12):1443–1450. doi: 10.1007/s40618-019-01058-x.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Higham CE, Olsson-Brown A, Carroll P, Cooksley T, Larkin J, Lorigan P, Morganstein D, Trainer PJ; Society for Endocrinology Clinical Committee. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Acute management of the endocrine complications of checkpoint inhibitor therapy. Endocr Connect. 2018;7(7):G1–G7. doi: 10.1530/EC-18-0068.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019;40(1):17–65. doi: 10.1210/er.2018-00006.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>U.S. Department Of Health And Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0 [Internet]. 2017 Nov 27. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Bisgaard Jørgensen L, Bastholt L, Yderstræde KB. Immunterapi med checkpointhæmmere og endokrinologiske bivirkninger. Ugeskrift for Laeger. 2018;179(2):132–136.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Majety P, Groysman A, Seery V, Shea M, Hou R. Monitoring Endocrine Complications of Immunotherapy: A Screening Tool. Cureus. 2022;14(7):e26859. doi: 10.7759/cureus.26859.</mixed-citation></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">Glibka AA, Mel'nichenko GA, Mikhina MS, Mazurina NV, Kharkevich GYu. Development of destructive thyroiditis and diabetes mellitus after three injections of pembrolizumab for skin melanoma. Problems of Endocrinology. 2021;67(2):20–27. doi: 10.14341/probl12698.</mixed-citation><mixed-citation xml:lang="ru">Глибка АА, Мельниченко ГА, Михина МС, Мазурина НВ, Харкевич ГЮ. Развитие деструктивного тиреоидита и сахарного диабета после трех введений пембролизумаба по поводу меланомы кожи. Проблемы Эндокринологии. 2021;67(2):20–27. doi: 10.14341/probl12698.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><mixed-citation>Rubino R, Marini A, Roviello G, Presotto EM, Desideri I, Ciardetti I, Brugia M, Pimpinelli N, Antonuzzo L, Mini E, Livi L, Maggi M, Peri A. Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy. Endocrine. 2021;74(1):172–179. doi: 10.1007/s12020-021-02750-w.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Presotto EM, Rastrelli G, Desideri I, Scotti V, Gunnella S, Pimpinelli N, Vaccher E, Bearz A, Di Costanzo F, Bruggia M, Mini E, Maggi M, Peri A. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. J Endocrinol Invest. 2020;43(3):337–345. doi: 10.1007/s40618-019-01112-8.</mixed-citation></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">Dedov II, Shestakova MV, Mayorova AYu, editors. [Algorithms of the specialized medical care to patients with diabetes mellitus]. 10th ed. Moscow; 2021. Russian. doi: 10.14341/DM12802.</mixed-citation><mixed-citation xml:lang="ru">Дедов ИИ, Шестакова МВ, Майорова АЮ, ред. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 10-й вып. М.; 2021. doi: 10.14341/DM12802.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><mixed-citation>Nogueira E, Newsom-Davis T, Morganstein DL. Immunotherapy-induced endocrinopathies: assessment, management and monitoring. Ther Adv Endocrinol Metab. 2019;10:2042018819896182. doi: 10.1177/2042018819896182.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Girotra M, Hansen A, Farooki A, Byun DJ, Min L, Creelan BC, Callahan MK, Atkins MB, Sharon E, Antonia SJ, West P, Gravell AE; Investigational Drug Steering Committee (IDSC) Immunotherapy Task Force collaboration. The Current Understanding of the Endocrine Effects From Immune Checkpoint Inhibitors and Recommendations for Management. JNCI Cancer Spectr. 2018;2(3):pky021. doi: 10.1093/jncics/pky021.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Thapi S, Leiter A, Galsky M, Gallagher EJ. Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis. J Immunother Cancer. 2019;7(1):248. doi: 10.1186/s40425-019-0729-3.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Inaba H, Ariyasu H, Okuhira H, Yamamoto Y, Hiroaki Akamatsu H, Katsuda M, Jinnin M, Hara I, Akamizu T. Endocrine dysfunctions during treatment of immune-checkpoint inhibitors. Trends Immunother, 2018;2(2):565. doi: 10.24294/ti.v2i2.606.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(2):173–182. doi: 10.1001/jamaoncol.2017.3064.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>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;187(6):G1–G21. doi: 10.1530/EJE-22-0689.</mixed-citation></ref><ref id="B21"><label>21.</label><citation-alternatives><mixed-citation xml:lang="en">Protsenko SA, Antimonik NYu, Ballyuzek MF, Bershteyn LM, Zhukova NV, Novik AV, Nosov DA, Petenko NN, Semenova AI, Chubenko VA, Kharkevich GYu, Yudin DI. [Practical guidelines on management of immune-mediated adverse events]. Malignant Tumours. 2022;12(3s2-2):203–241. Russian. doi: 10.18027/2224-5057-2022-12-3s2-203-241.</mixed-citation><mixed-citation xml:lang="ru">Проценко СА, Антимоник НЮ, Баллюзек МФ, Берштейн ЛМ, Жукова НВ, Новик АВ, Носов ДА, Петенко НН, Семенова АИ, Чубенко ВА, Харкевич ГЮ, Юдин ДИ. Практические рекомендации по управлению иммуноопосредованными нежелательными явлениями. Злокачественные опухоли. 2022;12(3s2-2):203–241. doi: 10.18027/2224-5057-2022-12-3s2-203-241.</mixed-citation></citation-alternatives></ref></ref-list></back></article>
