帕博利珠单抗致甲状腺功能减退症1例病例报道及文献复习
A Case Report and Literature Review of Hypothyroidism Caused by Pembrolizumab
DOI: 10.12677/acm.2024.1451597, PDF,   
作者: 贾慧萍, 苏永娥, 赵萌萌, 郭 转, 郝金荣, 袁淑梅, 张梦姣, 毛媛媛：西安市中心医院内分泌科，陕西 西安；延安大学医学院，陕西 延安；田竹芳*：西安市中心医院内分泌科，陕西 西安
关键词: 帕博利珠单抗；免疫检查点抑制剂；免疫相关不良事件；甲状腺功能减退症；Pembrolizumab； Immune Checkpoint Inhibitors； Immune-Related Adverse Events； Hypothyroidism
摘要: 近年来，肿瘤免疫治疗在临床应用越来越广泛，已经取得了较好的疗效。但在治疗过程中可能会产生免疫相关不良事件(Immue-Related Adverse Events, irAEs)，帕博利珠单抗属于免疫检查点抑制剂(Immune Checkpoint Inhibitors, ICIs)里的PD-1抑制剂。甲状腺功能减退症是免疫相关内分泌毒性常见的一种。本文报告一例帕博利珠单抗导致甲状腺功能减退症，结合相关文献对免疫检查点抑制剂相关的甲状腺功能减退症进行复习，为临床医生应对免疫相关不良事件提供更多经验。
Abstract: In recent years, tumor immunotherapy has been applied more and more widely in clinical practice, and has achieved good curative effect. However, immune-related adverse events (irAEs) may occur during treatment. Pembrolizumab belongs to the PD-1 inhibitor in the immune checkpoint inhibitors (ICIs). Hypothyroidism is a common type of immune-related endocrine toxicity. This paper reports a case of pembrolizumab-induced hypothyroidism, and reviews immune checkpoint inhibitor-related hypothyroidism in conjunction with relevant literature to provide clinicians with more experience in dealing with immune-related adverse events.
文章引用：贾慧萍, 苏永娥, 赵萌萌, 郭转, 郝金荣, 袁淑梅, 张梦姣, 毛媛媛, 田竹芳. 帕博利珠单抗致甲状腺功能减退症1例病例报道及文献复习[J]. 临床医学进展, 2024, 14(5): 1627-1632. https://doi.org/10.12677/acm.2024.1451597

参考文献

[1] Chalan, P., Di Dalmazi, G., Pani, F., et al. (2018) Thyroid Dysfunctions Secondary to Cancer Immunotherapy. Journal of Endocrinological Investigation, 41, 625-638. [Google Scholar] [CrossRef] [PubMed]
[2] Cuenca, D., Rodríguez-Meléndez, E., Aguilar-Soto, M., et al. (2021) Incidence and Clinical Characteristics of Thyroid Abnormalities in Cancer Patients Treated with Immune Checkpoint Inhibitors. Gaceta Médica De México, 157, 305-310. [Google Scholar] [CrossRef] 
[3] Darnell, E.P., Mooradian, M.J., Baruch, E.N., et al. (2020) Immune-Related Adverse Events (IrAEs): Diagnosis, Management, and Clinical Pearls. Current Oncology Reports, 22, Article No. 39. [Google Scholar] [CrossRef] [PubMed]
[4] Haanen, J., Obeid, M., Spain, L., et al. (2022) Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up. Annals of Oncology, 33, 1217-1238. [Google Scholar] [CrossRef] [PubMed]
[5] Barroso-Sousa, R., Barry, W.T., Garrido-Castro, A.C., et al. (2018) Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-Analysis. JAMA Oncology, 4, 173-182. [Google Scholar] [CrossRef] [PubMed]
[6] Arnaud-Coffin, P., Maillet, D., Gan, H.K., et al. (2019) A Systematic Review of Adverse Events in Randomized Trials Assessing Immune Checkpoint Inhibitors. International Journal of Cancer, 145, 639-648. [Google Scholar] [CrossRef] [PubMed]
[7] Byun, D.J., Wolchok, J.D., Rosenberg, L.M., et al. (2017) Cancer Immunotherapy—Immune Checkpoint Blockade and Associated Endocrinopathies. Nature Reviews Endocrinology, 13, 195-207. [Google Scholar] [CrossRef] [PubMed]
[8] Ferrari, S.M., Fallahi, P., Galetta, F., et al. (2018) Thyroid Disorders Induced by Checkpoint Inhibitors. Reviews in Endocrine and Metabolic Disorders, 19, 325-333. [Google Scholar] [CrossRef] [PubMed]
[9] Sznol, M., Postow, M.A., Davies, M.J., et al. (2017) Endocrine-Related Adverse Events Associated with Immune Checkpoint Blockade and Expert Insights on Their Management. Cancer Treatment Reviews, 58, 70-76. [Google Scholar] [CrossRef] [PubMed]
[10] Muir, C.A., Menzies, A.M., Clifton-Bligh, R., et al. (2020) Thyroid Toxicity Following Immune Checkpoint Inhibitor Treatment in Advanced Cancer. Thyroid, 30, 1458-1469. [Google Scholar] [CrossRef] [PubMed]
[11] 罗景梅, 杨中策, 潘俐, 张丽华. 免疫检查点抑制剂所致内分泌不良反应处理流程研究进展[J]. 解放军医学杂志, 2021(2): 200-206.
[12] Rubino, R., Marini, A., Roviello, G., et al. (2021) Endocrine-Related Adverse Events in a Large Series of Cancer Patients Treated with Anti-PD1 Therapy. Endocrine, 74, 172-179. [Google Scholar] [CrossRef] [PubMed]
[13] Li, X., Wang, X., Wang, S., et al. (2023) Thyroid Dysfunction Induced by Immune Checkpoint Inhibitors and Tumor Progression during Neoadjuvant Therapy of Non-Small Cell Lung Cancer: A Case Report and Literature Review. Oncology Letters, 26, Article No. 496. [Google Scholar] [CrossRef] [PubMed]
[14] Wang, Y., Wang, C., Qiu, J., et al. (2022) Targeting CD96 Overcomes PD-1 Blockade Resistance by Enhancing CD8 TIL Function in Cervical Cancer. Journal for Immunotherapy of Cancer, 10, e003667. [Google Scholar] [CrossRef] [PubMed]
[15] Meng, X., Liu, X., Guo, X., et al. (2018) FBXO38 Mediates PD-1 Ubiquitination and Regulates Anti-Tumour Immunity of T Cells. Nature, 564, 130-135. [Google Scholar] [CrossRef] [PubMed]
[16] Bhardwaj, M., Chiu, M.N. and Pilkhwal Sah, S. (2022) Adverse Cutaneous Toxicities by PD-1/PD-L1 Immune Checkpoint Inhibitors: Pathogenesis, Treatment, and Surveillance. Cutaneous and Ocular Toxicology, 41, 73-90. [Google Scholar] [CrossRef] [PubMed]
[17] Tang, Q., Chen, Y., Li, X., et al. (2022) The Role of PD-1/PD-L1 and Application of Immune-Checkpoint Inhibitors in Human Cancers. Frontiers in Immunology, 13, Article ID: 964442. [Google Scholar] [CrossRef] [PubMed]
[18] Suijkerbuijk, K.P.M., Kapiteijn, E. and Verheijden, R.J. (2020) Management of Immune-Related Adverse Events Affecting Outcome in Patients Treated with Checkpoint Inhibitors. JAMA Oncology, 6, 1300-1301. [Google Scholar] [CrossRef] [PubMed]
[19] Kobayashi, T., Iwama, S., Yasuda, Y., et al. (2018) Patients with Antithyroid Antibodies Are Prone to Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. Journal of the Endocrine Society, 2, 241-251. [Google Scholar] [CrossRef] [PubMed]
[20] Osorio, J.C., Ni, A., Chaft, J.E., et al. (2017) Antibody-Mediated Thyroid Dysfunction during T-Cell Checkpoint Blockade in Patients with Non-Small-Cell Lung Cancer. Annals of Oncology, 28, 583-589. [Google Scholar] [CrossRef] [PubMed]
[21] Fentiman, I.S., Balkwill, F.R., Thomas, B.S., et al. (1988) An Autoimmune Aetiology for Hypothyroidism Following Interferon Therapy for Breast Cancer. European Journal of Cancer and Clinical Oncology, 24, 1299-1303. [Google Scholar] [CrossRef] [PubMed]
[22] Lowndes, S.A., Asher, R. and Middleton, M.R. (2010) Thyrotoxicosis with Pegylated Interferon Alfa-2b. Archives of Dermatology, 146, 1273-1275. [Google Scholar] [CrossRef] [PubMed]
[23] Scalzo, S., Gengaro, A., Boccoli, G., et al. (1990) Primary Hypothyroidism Associated with Interleukin-2 and Interferon Alpha-2 Therapy of Melanoma and Renal Carcinoma. European Journal of Cancer and Clinical Oncology, 26, 1152-1156. [Google Scholar] [CrossRef] 
[24] Atkins, M.B., Mier, J.W., Parkinson, D.R., et al. (1988) Hypothyroidism after Treatment with Interleukin-2 and Lymphokine-Activated Killer Cells. New England Journal of Medicine, 318, 1557-1563. [Google Scholar] [CrossRef] 
[25] Abdel-Rahman, O., ElHalawani, H. and Fouad, M. (2016) Risk of Endocrine Complications in Cancer Patients Treated with Immune Check Point Inhibitors: A Meta-Analysis. Future Oncology, 12, 413-425. [Google Scholar] [CrossRef] [PubMed]
[26] Larkin, J., Chiarion-Sileni, V., Gonzalez, R., et al. (2015) Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. New England Journal of Medicine, 373, 23-34. [Google Scholar] [CrossRef] 
[27] Hellmann, M.D., Rizvi, N.A., Goldman, J.W., et al. (2017) Nivolumab plus Ipilimumab as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer (CheckMate 012): Results of an Open-Label, Phase 1, Multicohort Study. The Lancet Oncology, 18, 31-41. [Google Scholar] [CrossRef] 
[28] Morris, G.P., Brown, N.K. and Yi-Chi, M.K. (2009) Naturally-Existing CD4 CD25 Foxp3 Regulatory T Cells Are Required for Tolerance to Experimental Autoimmune Thyroiditis Induced by Either Exogenous or Endogenous Autoantigen. Journal of Autoimmunity, 33, 68-76. [Google Scholar] [CrossRef] [PubMed]
[29] Francisco, L.M., Sage, P.T. and Sharpe, A.H. (2010) The PD-1 Pathway in Tolerance and Autoimmunity. Immunological Reviews, 236, 219-242. [Google Scholar] [CrossRef] 
[30] Yamauchi, I., Sakane, Y., Fukuda, Y., et al. (2017) Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study. Thyroid, 27, 894-901. [Google Scholar] [CrossRef] [PubMed]
[31] Delivanis, D.A., Gustafson, M.P., Bornschlegl, S., et al. (2017) Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights into Underlying Involved Mechanisms. The Journal of Clinical Endocrinology & Metabolism, 102, 2770-2780. [Google Scholar] [CrossRef] [PubMed]

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