Prevalence, risk factors and features of the course of thyroid dysfunction induced by immunotherapy for cancer
- Authors: Zherebchikova K.Y.1, Soltakhanova M.O.1, Sych Y.P.1, Sekacheva M.I.1, Fadeev V.V.1, Dolidze M.V.2, Repetunov G.A.3, Vilensky A.A.4
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Affiliations:
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
- Voronezh State Medical University named after N.N. Burdenko
- Endocrinology Dispensary of the Moscow Healthcare Department
- Lomonosov Moscow State University
- Issue: Vol 32, No 2 (2025)
- Pages: 109-115
- Section: Original articles
- URL: https://journals.rcsi.science/2073-4034/article/view/294216
- DOI: https://doi.org/10.18565/pharmateca.2025.2.109-115
- ID: 294216
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Abstract
Background: The use of immune checkpoint inhibitors (ICPIs) is associated with the risk of endocrine adverse events (AEs).
Objective: Determination of the incidence, assessment of the structure, timing and predictors of development of immune related thyroid pathology during therapy with anti-PD1/ PDL1 drugs.
Materials and methods: The prospective study involved 235 patients aged 23 to 88 years without thyroid dysfunction, who were first treated with drugs from the anti-PD1/ PDL1 group for various types of malignant neoplasms. Thyroid function was assessed initially and every month throughout the treatment period. The average follow-up period was 52 weeks. The structure, incidence, time of manifestation and predictors of immune related thyroidopathy were assessed.
Results: Immune related thyroiditis was detected in 22.1% of patients, in half the pathology manifested itself in the thyrotoxic phase, in the other half - in the hypothyroid phase. The average time from the start of treatment to the development of thyroidopathy was 7.75 weeks. No predictors of the development of immune related thyroid pathology were identified. All patients with immune related thyroiditis developed manifest hypothyroidism as an outcome. All patients with hypothyroidism were prescribed replacement therapy with levothyroxine, and beta-blockers in the thyrotoxic phase of thyroiditis. In most cases, thyroiditis was asymptomatic and did not require cancellation or suspension of ICTI therapy.
Conclusion: The incidence of immune related thyroiditis was 22.1%. Further studies are required to more accurately identify predictors of the development of immune related thyroid pathology in order to determine the optimal management tactics for this group of patients.
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##article.viewOnOriginalSite##About the authors
Kristina Yu. Zherebchikova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Author for correspondence.
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0000-0003-0292-5907
Teaching Assistant at Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine
Russian Federation, MoscowMadina O. Soltakhanova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0009-0004-2816-0943
Clinical Resident
Russian Federation, MoscowYulia P. Sych
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0000-0002-7000-0095
Cand. Sci. (Med.), Associate Professor at the Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine
Russian Federation, MoscowMarina I. Sekacheva
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0000-0003-0015-7094
Dr. Sci. (Med.), Professor, Director of the Institute of Personalized Medicine, Head of the Center for Personalized Oncology
Russian Federation, MoscowValentin V. Fadeev
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0000-0002-2504-7468
r. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Medical Sciences, Head of the Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine
Russian Federation, MoscowMarina V. Dolidze
Voronezh State Medical University named after N.N. Burdenko
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0009-0003-5663-3448
Clinical Resident
Russian Federation, VoronezhGeorgy A. Repetunov
Endocrinology Dispensary of the Moscow Healthcare Department
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0009-0009-4108-3782
Endocrinologist
Russian Federation, MoscowAleksey A. Vilensky
Lomonosov Moscow State University
Email: k.y.zherebchikova@gmail.com
ORCID iD: 0000-0002-3094-7671
Head of the Department of Antitumor Drug Therapy of the Medical Scientific and Educational Center
Russian Federation, MoscowReferences
- Sanmamed M.F., Chen L. A paradigm shift in cancer immunotherapy: from enhancement to normalization. Cell. 2018;175(2):313–326. doi: 10.1016/j.cell.2018.09.035.
- Fanciulli G., Di Molfetta S., Dotto A., et al. Emerging therapies in pheochromocytoma and paraganglioma: immune checkpoint inhibitors in the starting blocks. J Clin Med. 2020;10(1):88. doi: 10.3390/jcm10010088.
- Higham C.E., Olsson-Brown A., Carroll P., et al. & Society for Endocrinology Clinical Committee. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Acute management of the endocrine complications of checkpoint inhibitor therapy. Endocrine Connections. 2018;7(7):G1-G7. doi: 10.1530/EC-18-0068.
- Amin M.B., Greene F.L., Edge S.B., et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more «personalized» approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–99. doi: 10.3322/caac.21388.
- Thompson J.A., Schneider B.J., Brahmer J., et al. NCCN Guidelines® insights: management of immunotherapy-related toxicities, Version 2.2024. J Natl Compr Canc Netw. 2024;22(9):582–592. doi: 10.6004/jnccn.2024.0057.
- Cancer Institute N. Common terminology criteria for adverse events (CTCAE) common terminology criteria for adverse events (CTCAE) v5. 0. 2017. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed: 01.06.2023.
- Elshafie O., Khalil A.B., Salman B., et al. Immune checkpoint inhibitors-induced endocrinopathies: assessment, management and monitoring in a comprehensive cancer centre. Endocrinol Diabetes Metab. 2024;7(4):e00505. doi: 10.1002/edm2.505.
- Muir C.A. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment. J. Clin. Endocrinol. Metab. 2021;106(9):E3704–E3713. doi: 10.3892/ol.2023.14083.
- Girotra M., Hansen A., Farooki A., et al. The current understanding of the endocrine effects from immune checkpoint inhibitors and recommendations for management. JNCI cancer Spectr. 2018;2(3). doi: 10.1093/jncics/pky021.
- Zhai Y., Ye X., Hu F., et al. Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system. J Immunotherapy Cancer 2019;7:286. doi: 10.1186/s40425-019-0754-2.
- Ruggeri R.M., Spagnolo C.C., Alibrandi A., et al. Predictors of thyroid adverse events during cancer immunotherapy: a real-life experience at a single center. J Endocrinol Invest. 2023;46(11):2399–2409. doi: 10.1007/s40618-023-02096-2.
- Iwama S., Kobayashi T., Yasuda Y., Arima H. Immune checkpoint inhibitor-related thyroid dysfunction. Best Pract Res Clin Endocrinol Metab. 2022;36(3):101660. doi: 10.1016/j.beem.2022.101660.
- Presotto E.M., Rastrelli G., Desideri I., et al. 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.
- Barroso-Sousa R., Barry W.T., Garrido-Castro A.C., et al. 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.
- Chang L.S., Barroso-Sousa R., Tolaney S.M., et al. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev. 2019;40(1):17–65. doi: 10.1210/er.2018-00006.
- Inaba H., Ariyasu H., Okuhira H., et al. Endocrine dysfunctions during treatment of immune-checkpoint inhibitors. Trends Immunother. 2020;4(1):18–26. doi: 10.24294/ti.v2.i2.606.
- Osorio J.C., Ni A., Chaft J.E.,et al. Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol Off J Eur Soc Med Oncol. 2017;28(3):583–589. doi: 10.1093/annonc/mdw640.
- Inaba H., Ariyasu H., Takeshima K., et al. Comprehensive research on thyroid diseases associated with autoimmunity: autoimmune thyroid diseases, thyroid diseases during immune-checkpoint inhibitors therapy, and immunoglobulin-G4-associated thyroid diseases. Endocr J. 2029;66(10):843–852. doi: 10.1507/endocrj.EJ19-0234.
- Mazarico I., Capel I., Giménez-Palop O., et al. 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.
- Ferrari S.M., Fallahi P., Galetta F., et al. Thyroid disorders induced by checkpoint inhibitors. Rev Endocr Metab Disord. 2018;19(4):325–333. doi: 10.1007/s11154-018-9463-2.
- Юдин Д.И., Лактионов К.К., Саранцева К.А., и др. Иммуноопосредованная эндокринопатия у пациентов на фоне лечения ингибиторами контрольных точек. Медицинский Совет. 2020;9:16–24. [Yudin D.I., Laktionov K.K., Sarantseva K.A., et al. Immuno-related endocrinopathy in patients treated with immune checkpoint inhibitors. Meditsinskiy sovet = Medical Council. 2020;(9):16-24. (In Russ.)]. doi: 10.21518/2079-701X-2020-9-16-24.
- Поддубская Е.В., Секачева М.И., Гурьянова А.А. Эндокринологические осложнения ингибиторов контрольных точек иммунитета: результаты одноцентрового исследования. Сеченовский вестник. 2019;10(4):4–11. [Poddubskaya E.V., Sekacheva M.I., Guryanova A.A. Endocrinological complications of immune checkpoint inhibitors: results of a single-center study. Sechenov Bulletin. 2019;10(4):4–11. (In Russ.)]. doi: 10.47093/22187332.2019.4.4-11.
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