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Abstract

Background

Immune Checkpoint Inhibitor (ICPi) therapy has revolutionized cancer treatment but can lead to immune-related adverse events (irAE), including thyroid dysfunction. The impact of ICPi on patients with pre-existing autoimmune thyroid diseases (PATD), particularly the development of Graves' disease, remains poorly understood.

Case Description

We provide the first complete case of Graves' disease with ICPi therapy in a patient who already had Hashimoto's thyroiditis.. The patient, a 52-year-old male, was diagnosed with lung adenocarcinoma and received Atezolizumab. Clinical evaluation revealed hyperthyroidism, confirmed by elevated thyroid hormones and autoantibodies (TRAb and TSAb). The patient was managed with methimazole and demonstrated a transient hyperthyroid phase followed by persistent hypothyroidism. Only 16 confirmed cases of Graves' disease induced by ICPi were reported. We conducted a review to investigate the clinical characteristics, risk factors, and prognosis trends associated with ICPi-induced Graves disease in PTAD patients. Additionally, changes in thyroid function and autoantibodies during and after ICPi treatment are examined.

Conclusion

This case underscores the importance of monitoring thyroid function and autoantibodies in patients with PATD undergoing ICPi therapy. The findings suggest distinct differences in the humoral immune response between ICPi-induced and spontaneous Graves' disease, necessitating further research into autoantibody dynamics and their relationship with cellular immunity in these patients.

© 2025 The Author(s). Published by Bentham Science Publishers
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2025-02-10
2025-07-23

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References

  1. Wright J.J. Powers A.C. Johnson D.B. Endocrine toxicities of immune checkpoint inhibitors. Nat. Rev. Endocrinol. 2021 17 7 389 399 10.1038/s41574‑021‑00484‑3 33875857
    [Google Scholar]
  2. Chiloiro S. Bianchi A. Giampietro A. Milardi D. De Marinis L. Pontecorvi A. The changing clinical spectrum of endocrine adverse events in cancer immunotherapy. Trends Endocrinol. Metab. 2022 33 2 87 104 10.1016/j.tem.2021.10.009 34895977
    [Google Scholar]
  3. Ramos-Casals M. Sisó-Almirall A. Immune-related adverse events of immune checkpoint inhibitors. Ann. Intern. Med. 2024 177 2 ITC17 ITC32 10.7326/AITC202402200 38346306
    [Google Scholar]
  4. Wang S.J. Dougan S.K. Dougan M. Immune mechanisms of toxicity from checkpoint inhibitors. Trends Cancer 2023 9 7 543 553 10.1016/j.trecan.2023.04.002 37117135
    [Google Scholar]
  5. Tison A. Garaud S. Chiche L. Cornec D. Kostine M. Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases. Nat. Rev. Rheumatol. 2022 18 11 641 656 10.1038/s41584‑022‑00841‑0 36198831
    [Google Scholar]
  6. Sparks J.A. Pre-existing autoimmune diseases and immune checkpoint inhibitors for cancer treatment: Considerations about initiation, flares, immune-related adverse events, and cancer progression. Rheum. Dis. Clin. North Am. 2024 50 2 147 159 10.1016/j.rdc.2024.01.001 38670718
    [Google Scholar]
  7. Sumimoto H. Noda S. Koide H. Douke Y. Sakai K. Nishikawa A. Tomioka A. Hori M. Nakato H. Kimura Y. Tokuda A. Takano A. Teramoto K. Murata S. Daigo Y. Pre-existing autoimmune disease as a risk factor for immune-related adverse events in cancer patients receiving immune checkpoint inhibitors. PLoS One 2024 19 7 e0306995 10.1371/journal.pone.0306995 39012903
    [Google Scholar]
  8. Kehl K.L. Yang S. Awad M.M. Palmer N. Kohane I.S. Schrag D. Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer. Cancer Immunol. Immunother. 2019 68 6 917 926 10.1007/s00262‑019‑02321‑z 30877325
    [Google Scholar]
  9. Zhang K. Kong X. Li Y. Wang Z. Zhang L. Xuan L. PD-1/PD-L1 inhibitors in patients with preexisting autoimmune diseases. Front. Pharmacol. 2022 13 854967 10.3389/fphar.2022.854967 35370736
    [Google Scholar]
  10. Iwama S. Kobayashi T. Yasuda Y. Arima H. Immune checkpoint inhibitor-related thyroid dysfunction. Best Pract. Res. Clin. Endocrinol. Metab. 2022 36 3 101660 10.1016/j.beem.2022.101660 35501263
    [Google Scholar]
  11. Lu D. Yao J. Yuan G. Gao Y. Zhang J. Guo X. Immune checkpoint inhibitor-related new-onset thyroid dysfunction: A retrospective analysis using the US FDA adverse event reporting system. Oncologist 2022 27 2 e126 e132 10.1093/oncolo/oyab043 35641200
    [Google Scholar]
  12. Wiersinga W.M. Poppe K.G. Effraimidis G. Hyperthyroidism: Aetiology, pathogenesis, diagnosis, management, complications, and prognosis. Lancet Diabetes Endocrinol. 2023 11 4 282 298 10.1016/S2213‑8587(23)00005‑0 36848916
    [Google Scholar]
  13. Petranović Ovčariček P. Görges R. Giovanella L. Autoimmune thyroid diseases. Semin. Nucl. Med. 2024 54 2 219 236 10.1053/j.semnuclmed.2023.11.002 38044176
    [Google Scholar]
  14. Grixti L. Lane L.C. Pearce S.H. The genetics of Graves’ disease. Rev. Endocr. Metab. Disord. 2024 25 1 203 214 10.1007/s11154‑023‑09848‑8 38108994
    [Google Scholar]
  15. Pitoia F. Trimboli P. New insights in thyroid diagnosis and treatment. Rev. Endocr. Metab. Disord. 2024 25 1 1 3 10.1007/s11154‑023‑09859‑5 38041785
    [Google Scholar]
  16. Lee S.Y. Pearce E.N. Hyperthyroidism. JAMA 2023 330 15 1472 1483 10.1001/jama.2023.19052 37847271
    [Google Scholar]
  17. Lanzolla G. Marinò M. Menconi F. Graves disease: Latest understanding of pathogenesis and treatment options. Nat. Rev. Endocrinol. 2024 20 11 647 660 10.1038/s41574‑024‑01016‑5 39039206
    [Google Scholar]
  18. Azmat U. Liebner D. Joehlin-Price A. Agrawal A. Nabhan F. Treatment of ipilimumab induced Graves’ disease in a patient with metastatic melanoma. Case Rep. Endocrinol. 2016 2016 1 4 10.1155/2016/2087525 26881150
    [Google Scholar]
  19. de Filette J. Jansen Y. Schreuer M. Everaert H. Velkeniers B. Neyns B. Bravenboer B. Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab. J. Clin. Endocrinol. Metab. 2016 101 11 4431 4439 10.1210/jc.2016‑2300 27571185
    [Google Scholar]
  20. Gan E.H. Mitchell A.L. Plummer R. Pearce S. Perros P. Tremelimumab-induced graves hyperthyroidism
. Eur. Thyroid J. 2017 6 3 167 170 10.1159/000464285 28785544
    [Google Scholar]
  21. Narayen G. Lieb D. Pembrolizumab-related graves' disease: A rare adverse effect of an anti-PD-1 antibody cancer immunotherapy. J Endocr Soc 2019 3 Suppl 1 SAT-584 10.1210/js.2019‑SAT‑584
    [Google Scholar]
  22. Brancatella A. Viola N. Brogioni S. Montanelli L. Sardella C. Vitti P. Marcocci C. Lupi I. Latrofa F. Graves’ disease induced by immune checkpoint inhibitors: A case report and review of the literature. Eur. Thyroid J. 2019 8 4 192 195 10.1159/000501824 31602361
    [Google Scholar]
  23. Yajima K. Akise Y. A case report of Graves’ disease induced by the anti-human programmed cell death-1 monoclonal antibody pembrolizumab in a bladder cancer patient. Case Rep. Endocrinol. 2019 2019 1 5 10.1155/2019/2314032 31772785
    [Google Scholar]
  24. Iadarola C. Croce L. Quaquarini E. Teragni C. Pinto S. Bernardo A. Fonte R. Marinò M. Rotondi M. Chiovato L. Nivolumab induced thyroid dysfunction: Unusual clinical presentation and challenging diagnosis. Front. Endocrinol. 2019 9 813 10.3389/fendo.2018.00813 30705667
    [Google Scholar]
  25. Yamada H. Okajima F. Onda T. Fujimori S. Emoto N. Sugihara H. New-onset graves’ disease after the initiation of nivolumab therapy for gastric cancer: A case report. BMC Endocr. Disord. 2020 20 1 132 10.1186/s12902‑020‑00613‑5 32847555
    [Google Scholar]
  26. Kurihara S. Oikawa Y. Nakajima R. Satomura A. Tanaka R. Kagamu H. Shimada A. Simultaneous development of Graves’ disease and type 1 diabetes during anti‐programmed cell death‐1 therapy: A case report. J. Diabetes Investig. 2020 11 4 1006 1009 10.1111/jdi.13212 31926048
    [Google Scholar]
  27. Peiffert M. Cugnet-Anceau C. Dalle S. Chikh K. Assaad S. Disse E. Raverot G. Borson-Chazot F. Abeillon-du Payrat J. Graves’ disease during immune checkpoint inhibitor therapy (a case series and literature review). Cancers 2021 13 8 1944 10.3390/cancers13081944 33920721
    [Google Scholar]
  28. Reddy C. Zena M. Title: Case of hyperthyroidism in a patient on Anti-PD-1 (programmed cell death receptor-1 blocking antibody) therapy caused by destructive thyroiditis followed by Graves’ disease. J. Endocr. Soc. 2021 5 Suppl. 1 A968 A969 10.1210/jendso/bvab048.1979
    [Google Scholar]
  29. Alqaisi S. Rahman A. A rare case of pembrolizumab-associated Graves’ disease. Cureus 2023 15 2 e34696 10.7759/cureus.34696 36909047
    [Google Scholar]
  30. Muir C.A. Wood C.C.G. Clifton-Bligh R.J. Long G.V. Scolyer R.A. Carlino M.S. Menzies A.M. Tsang V.H.M. Association of antithyroid antibodies in checkpoint inhibitor–associated thyroid immune–related adverse events. J. Clin. Endocrinol. Metab. 2022 107 5 e1843 e1849 10.1210/clinem/dgac059 35104870
    [Google Scholar]
  31. Chieng J.H.L. Htet Z.W. Zhao J.J. Tai E.S. Tay S.H. Huang Y. Wong A. Yang S.P. Clinical presentation of immune-related endocrine adverse events during immune checkpoint inhibitor treatment. Cancers 2022 14 11 2687 10.3390/cancers14112687 35681667
    [Google Scholar]
  32. Kimbara S. Fujiwara Y. Iwama S. Ohashi K. Kuchiba A. Arima H. Yamazaki N. Kitano S. Yamamoto N. Ohe Y. Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab. Cancer Sci. 2018 109 11 3583 3590 10.1111/cas.13800 30230649
    [Google Scholar]
  33. Wang Q. Wu T. Zhao R. Li Y. Chen X. Shen S. Zhang X. Development and validation of a prediction model for thyroid dysfunction in patients during immunotherapy. Endocr Pract 2024 30 10 943 950
    [Google Scholar]
  34. Zhou X. Iwama S. Kobayashi T. Ando M. Arima H. Risk of thyroid dysfunction in PD-1 blockade is stratified by the pattern of TgAb and TPOAb positivity at baseline. J. Clin. Endocrinol. Metab. 2023 108 10 e1056 e1062 10.1210/clinem/dgad231 37084392
    [Google Scholar]
  35. Mariani G. Tonacchera M. Grosso M. Orsolini F. Vitti P. Strauss H.W. The role of nuclear medicine in the clinical management of benign thyroid disorders, Part 1: Hyperthyroidism. J. Nucl. Med. 2021 62 3 304 312 10.2967/jnumed.120.243170 33008929
    [Google Scholar]
  36. Tywanek E. Michalak A. Świrska J. Zwolak A. Autoimmunity, new potential biomarkers and the thyroid gland—The perspective of Hashimoto’s thyroiditis and its treatment. Int. J. Mol. Sci. 2024 25 9 4703 10.3390/ijms25094703 38731922
    [Google Scholar]
  37. Krieger C.C. Kahaly G.J. Azam A. Klubo-Gwiezdzinska J. Neumann S. Gershengorn M.C. Graves’ autoantibodies exhibit different stimulating activities in cultures of thyrocytes and orbital fibroblasts not reflected by clinical assays. Thyroid 2022 32 1 90 96 34714162
    [Google Scholar]
  38. Stan M.N. Algeciras-Schimnich A. Murthy V. Thapa P. Araki N. Diagnostic utility of a new assay for thyroid stimulating immunoglobulins in Graves’ disease and thyroid eye disease. Thyroid 2022 32 2 170 176 10.1089/thy.2021.0299 34714163
    [Google Scholar]
  39. Kahaly G.J. Diana T. Kanitz M. Frommer L. Olivo P.D. Prospective trial of functional thyrotropin receptor antibodies in Graves disease. J. Clin. Endocrinol. Metab. 2020 105 4 e1006 e1014 10.1210/clinem/dgz292 31865369
    [Google Scholar]
  40. Napolitano G. Bucci I. Di Dalmazi G. Giuliani C. Non-conventional clinical uses of TSH receptor antibodies: The case of chronic autoimmune thyroiditis. Front. Endocrinol. 2021 12 769084 10.3389/fendo.2021.769084 34803929
    [Google Scholar]
  41. Nalla P. Young S. Sanders J. Carter J. Adlan M.A. Kabelis K. Chen S. Furmaniak J. Rees Smith B. Premawardhana L.D.K.E. Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease. Clin. Endocrinol. 2019 90 2 369 374 10.1111/cen.13908 30485487
    [Google Scholar]
  42. Bukhari S. Henick B.S. Winchester R.J. Lerrer S. Adam K. Gartshteyn Y. Maniar R. Lin Z. Khodadadi-Jamayran A. Tsirigos A. Salvatore M.M. Lagos G.G. Reiner S.L. Dallos M.C. Mathew M. Rizvi N.A. Mor A. Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors. Cell Rep. Med. 2023 4 1 100868 10.1016/j.xcrm.2022.100868 36513074
    [Google Scholar]
  43. Yasuda Y. Iwama S. Sugiyama D. Okuji T. Kobayashi T. Ito M. Okada N. Enomoto A. Ito S. Yan Y. Sugiyama M. Onoue T. Tsunekawa T. Ito Y. Takagi H. Hagiwara D. Goto M. Suga H. Banno R. Takahashi M. Nishikawa H. Arima H. CD4 + T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice. Sci. Transl. Med. 2021 13 593 eabb7495 10.1126/scitranslmed.abb7495 33980577
    [Google Scholar]
  44. Kotwal A. Gustafson M.P. Bornschlegl S. Kottschade L. Delivanis D.A. Dietz A.B. Gandhi M. Ryder M. Immune checkpoint inhibitor-induced thyroiditis is associated with increased intrathyroidal T lymphocyte subpopulations. Thyroid 2020 30 10 1440 1450 10.1089/thy.2020.0075 32323619
    [Google Scholar]
  45. Taylor J. Gandhi A. Gray E. Zaenker P. Checkpoint inhibitor immune-related adverse events: A focused review on autoantibodies and B cells as biomarkers, advancements and future possibilities. Front. Immunol. 2023 13 991433 10.3389/fimmu.2022.991433 36713389
    [Google Scholar]
  46. Vargas-Uricoechea H. Molecular mechanisms in autoimmune thyroid disease. Cells 2023 12 6 918 10.3390/cells12060918 36980259
    [Google Scholar]
  47. Inaba H. De Groot L.J. Akamizu T. Thyrotropin receptor epitope and human leukocyte antigen in Graves’ disease. Front. Endocrinol. 2016 7 120 10.3389/fendo.2016.00120 27602020
    [Google Scholar]
  48. Muller I. Willis M. Healy S. Nasser T. Loveless S. Butterworth S. Zhang L. Draman M.S. Taylor P.N. Robertson N. Dayan C.M. Ludgate M.E. Longitudinal characterization of autoantibodies to the thyrotropin receptor (TRAb) during alemtuzumab therapy: Evidence that TRAb may precede thyroid dysfunction by many years. Thyroid 2018 28 12 1682 1693 10.1089/thy.2018.0232 30351224
    [Google Scholar]
  49. Dwivedi S.N. Kalaria T. Buch H. Thyroid autoantibodies. J. Clin. Pathol. 2023 76 1 19 28 10.1136/jcp‑2022‑208290 36270794
    [Google Scholar]
  50. Hu X. Wang L. Shang B. Wang J. Sun J. Liang B. Su L. You W. Jiang S. Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors. Front. Immunol. 2023 14 1094414 10.3389/fimmu.2023.1094414 36949956
    [Google Scholar]
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ICPi-Induced Graves' Disease with Pre-existing Autoimmune Thyroid Disorders: A Case Report and Literature Review
Bentham Science Publishers ; https://doi.org/10.2174/0118715303317264250116095028
/content/journals/emiddt/10.2174/0118715303317264250116095028
/content/journals/emiddt/10.2174/0118715303317264250116095028
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  • Article Type:     Case Report
Keywords: autoantibody ; autoimmune disease ; immune checkpoint inhibitor ; thyroid toxicity ; Graves' disease

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