免疫检查点抑制剂相关甲状腺毒症

武凌鸽; 徐燕; 李乃适

doi:10.3969/j.issn.1674-9081.2020.00.004

免疫检查点抑制剂相关甲状腺毒症

doi: 10.3969/j.issn.1674-9081.2020.00.004

1.
中国医学科学院北京协和医学院北京协和医院内分泌科国家卫健委内分泌重点实验室, 北京 100730
2.
中国医学科学院北京协和医学院北京协和医院呼吸与危重症医学科, 北京 100730

基金项目:

国家“十三五”重大新药创制专项子课题“创新药物临床评价示范性平台建设” 2019ZX09734001-002

中国医学科学院医学与健康科技创新工程重大协同创新项目 2017-I2M-1-009

详细信息

通讯作者:
李乃适电话：010-69155073, E-mail：LNS@medmail.com.cn

中图分类号: R979.5; R581
计量
- 文章访问数: 663
- HTML全文浏览量: 140
- PDF下载量: 43
- 被引次数: 0
出版历程
- 收稿日期: 2020-04-13
- 录用日期: 2020-05-14
- 网络出版日期: 2020-08-14
- 刊出日期: 2021-01-30

Thyrotoxicosis Related to Immune Checkpoint Inhibitors

WU Ling-ge¹,
XU Yan²,
LI Nai-shi^{1
, ,}

1.
Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission of the People's Republic of China, Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funds:

"13th Five-Year"National Science and Technology Major Project for New Drugs 2019ZX09734001-002

CAMS Innovation Fund for Medical Sciences 2017-I2M-1-009

More Information

Corresponding author: LI Nai-shi Tel: 86-10-69155073, E-mail: LNS@medmail.com.cn

摘要

摘要: 免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)是近年来恶性肿瘤治疗领域的一项重大突破。其通过针对T细胞的调节作用，增强抗肿瘤免疫反应，改善恶性肿瘤患者的预后，延长患者生存期，现已获批用于治疗多种肿瘤，但ICIs在应用过程中产生的甲状腺毒症是不容忽视的临床问题。本文对ICIs相关甲状腺毒症的发生机制、临床表现、处理对策等进行综述。
- 免疫检查点抑制剂 /
- 免疫相关不良反应 /
- 甲状腺毒症
Abstract: Immune checkpoint inhibitors (ICIs) have come out in recent years as a breakthrough of the treatments for malignant tumors by regulating T cells with the purpose of enhancing their anti-tumor response, which can improve prognosis and increase survival. However, thyrotoxicosis caused by ICIs has become a clinical problem that cannot be ignored. This review summarizes the pathogenic mechanisms, clinical manifesta-tions, and treatments of ICIs associated thyrotoxicosis.
- immune checkpoint inhibitors /
- immune-related adverse events /
- thyrotoxicosis
注释:

作者贡献：武凌鸽负责文献检索、数据分析及文章初稿撰写；李乃适、徐燕负责文章初稿修订；李乃适负责文章审校。

利益冲突 无

HTML全文

参考文献(56)

[1]	Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nat Rev Cancer, 2012, 12:252-64. doi: 10.1038/nrc3239
[2]	Sharma P, Allison JP. The future of immune checkpoint therapy[J]. Science, 2015, 348:56-61. doi: 10.1126/science.aaa8172
[3]	Momtaz P, Postow MA.Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1) receptor pathway[J]. Pharmgenomics Pers Med, 2014, 7:357-365. http://www.tandfonline.com/servlet/linkout?suffix=CIT0001&dbid=8&doi=10.1517%2F14740338.2015.1085969&key=25484597
[4]	Postow MA, Callahan MK, Wolchok JD. Immune Check-point Blockade in Cancer Therapy[J]. J Clin Oncol, 2015, 33:1974-1982. doi: 10.1200/JCO.2014.59.4358
[5]	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[J]. JAMA Oncol, 2018, 4:173-182. doi: 10.1001/jamaoncol.2017.3064
[6]	Surks MI, Chopra IJ, Mariash CN, et al.American Thyroid Association guidelines for use of laboratory tests in thyroid disorders[J]. JAMA, 1990, 263:1529-1532. doi: 10.1001/jama.1990.03440110095035
[7]	Sharma P, Hu-Lieskovan S, Wargo JA, et al.Primary, Adaptive, and Acquired Resistance to Cancer Immuno-therapy[J]. Cell, 2017, 168:707-723. doi: 10.1016/j.cell.2017.01.017
[8]	Reeves E, James E.Antigen processing and immune regulation in the response to tumours[J]. Immunology, 2017, 150:16-24. doi: 10.1111/imm.12675
[9]	Harding FA, McArthur JG, Gross JA, et al.CD28-media-ted signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones[J]. Nature, 1992, 356:607-609. doi: 10.1038/356607a0
[10]	Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity[J]. Nat Rev Immunol, 2004, 4:336-347. doi: 10.1038/nri1349
[11]	Fecher LA, Agarwala SS, Hodi FS, et al. Ipilimumab and its toxicities: a multidisciplinary approach[J]. Oncologist, 2013, 18:733-743. doi: 10.1634/theoncologist.2012-0483
[12]	Brahmer JR, Lacchetti C, Thompson JA. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Summary[J]. J Oncol Pract, 2018, 14:247-249. doi: 10.1200/JOP.18.00005
[13]	Barroso-Sousa R, Ott PA, Hodi FS, et al. Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management[J]. Cancer, 2018, 124:1111-1121. doi: 10.1002/cncr.31200
[14]	Delivanis DA, Gustafson MP, Bornschlegl S, et al.Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms[J]. J Clin Endocrinol Metab, 2017, 102:2770-2780. doi: 10.1210/jc.2017-00448
[15]	Angell TE, Min L, Wieczorek TJ, et al.Unique Cytologic Features of Thyroiditis Caused by Immune Checkpoint Inhibitor Therapy for Malignant Melanoma[J]. Genes Dis, 2018, 5:46-48. doi: 10.1016/j.gendis.2017.11.002
[16]	Yamauchi I, Sakane Y, Fukuda Y, et al.Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study[J]. Thyroid, 2017, 27:894-901. doi: 10.1089/thy.2016.0562
[17]	Inoue H, Park JH, Kiyotani K, et al. Intratumoral expres-sion levels of PD-L1, GZMA, and HLA-A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma[J]. Oncoimmunology, 2016, 5:e1204507. doi: 10.1080/2162402X.2016.1204507
[18]	Scott ES, Long GV, Guminski A, et al.The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma[J].Eur J Endocrinol, 2018, 178:173-180. doi: 10.1530/EJE-17-0810
[19]	Morganstein DL, Lai Z, Spain L, et al. Thyroid abnor-malities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma[J]. Clin Endocrinol (Oxf), 2017, 86:614-620. doi: 10.1111/cen.13297
[20]	Lee H, Hodi FS, Giobbie-Hurder A, et al. Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy[J]. Cancer Immunol Res, 2017, 5:1133-1140. doi: 10.1158/2326-6066.CIR-17-0208
[21]	Guaraldi F, La Selva R, Samà MT, et al. Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution[J]. J Endocrinol Invest, 2018, 41:549-556. doi: 10.1007/s40618-017-0772-1
[22]	Yamazaki H, Iwasaki H, Yamashita T, et al. Potential Risk Factors for Nivolumab-induced Thyroid Dysfunction[J]. In Vivo, 2017, 31:1225-1228.
[23]	Orlov S, Salari F, Kashat L, et al. Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies[J]. J Clin Endocrinol Metab, 2015, 100:1738-1741. doi: 10.1210/jc.2014-4560
[24]	O'Malley G, Lee HJ, Parekh S, et al. Rapid Evolution of Thyroid Dysfunction in Patients Treated with Nivolumab[J]. Endocr Pract, 2017, 23:1223-1231. doi: 10.4158/EP171832.OR
[25]	de Filette J, Jansen Y, Schreuer M, et al. Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab[J]. J Clin Endocrinol Metab, 2016, 101:4431-4439. doi: 10.1210/jc.2016-2300
[26]	Kimbara S, Fujiwara Y, Iwama S, et al.Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab[J].Cancer Sci, 2018, 109:3583-3590. doi: 10.1111/cas.13800
[27]	Osorio JC, Ni A, Chaft JE, et al.Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer[J]. Ann Oncol, 2017, 28:583-589. doi: 10.1093/annonc/mdw640
[28]	Kavvoura FK, Akamizu T, Awata T, et al. Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune thyroid disease: a meta-analysis[J]. J Clin Endocrinol Metab, 2007, 92:3162-3170. doi: 10.1210/jc.2007-0147
[29]	Azmat U, Liebner D, Joehlin-Price A, et al.Treatment of Ipilimumab Induced Graves' Disease in a Patient with Metastatic Melanoma[J].Case Rep Endocrinol, 2016:2087525. http://pubmedcentralcanada.ca/pmcc/articles/PMC4737013/
[30]	Heward JM, Allahabadia A, Armitage M, et al.The development of Graves' disease and the CTLA-4 gene on chromosome 2q33[J]. J Clin Endocrinol Metab, 1999, 84:2398-2401. http://www.ncbi.nlm.nih.gov/pubmed/10404810
[31]	Daroszewski J, Pawlak E, Karabon L, et al. Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms[J]. Eur J Endocrinol, 2009, 161:787-793. doi: 10.1530/EJE-09-0600
[32]	Ting WH, Chien MN, Lo FS, et al.Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study[J]. PLoS One, 2016, 11:e0154394. doi: 10.1371/journal.pone.0154394
[33]	Vaidya B, Imrie H, Perros P, et al. Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers suscepti-bility to thyroid associated orbitopathy[J]. Lancet, 1999, 354:743-744. doi: 10.1016/S0140-6736(99)01465-8
[34]	Buzzetti R, Nisticò L, Signore A, et al. CTLA-4 and HLA gene susceptibility to thyroid-associated orbitopathy[J]. Lancet, 1999, 354:1824. http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=2212292&site=ehost-live
[35]	Villanueva R, Inzerillo AM, Tomer Y, et al. Limited genetic susceptibility to severe Graves' ophthalmopathy: no role for CTLA-4 but evidence for an environmental etiology[J]. Thyroid, 2000, 10:791-798. doi: 10.1089/thy.2000.10.791
[36]	Allahabadia A, Heward JM, Nithiyananthan R, et al.MHC class Ⅱ region, CTLA4 gene, and ophthalmopathy in patients with Graves' disease[J]. Lancet, 2001, 358:984-985. doi: 10.1016/S0140-6736(01)06125-6
[37]	Kotsa K, Watson PF, Weetman AP. A CTLA-4 gene polymorphism is associated with both Graves disease and autoimmune hypothyroidism[J].Clin Endocrinol (Oxf), 1997, 46:551-554. doi: 10.1046/j.1365-2265.1997.1710996.x
[38]	Bednarczuk T, Gopinath B, Ploski R, et al.Susceptibility genes in Graves' ophthalmopathy: searching for a needle in a haystack?[J]. Clin Endocrinol (Oxf), 2007, 67:3-19. doi: 10.1111/j.1365-2265.2007.02854.x
[39]	Mitchell AL, Cordell HJ, Soemedi R, et al.Programmed death ligand 1 (PD-L1) gene variants contribute to autoimmune Addison's disease and Graves' disease susceptibility[J]. J Clin Endocrinol Metab, 2009, 94:5139-5145. doi: 10.1210/jc.2009-1404
[40]	Hayashi M, Kouki T, Takasu N, et al.Association of an A/C single nucleotide polymorphism in programmed cell death-ligand 1 gene with Graves' disease in Japanese patients[J]. Eur J Endocrinol, 2008, 158:817-822. doi: 10.1530/EJE-07-0649
[41]	de Filette J, Andreescu CE, Cools F, et al. A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors[J].Horm Metab Res, 2019, 51:145-156. doi: 10.1055/a-0843-3366
[42]	Gan EH, Mitchell AL, Plummer R, et al.Tremelimumab-Induced Graves Hyperthyroidism[J]. Eur Thyroid J, 2017, 6:167-170. doi: 10.1159/000464285
[43]	Brancatella A, Viola N, Brogioni S, et al. Graves' Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature[J]. Eur Thyroid J, 2019, 8:192-195. doi: 10.1159/000501824
[44]	Iadarola C, Croce L, Quaquarini E, et al. Nivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis[J]. Front Endocrinol (Lausanne), 2019, 9:813. doi: 10.3389/fendo.2018.00813
[45]	Min L, Vaidya A, Becker C.Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy[J]. Eur J Endocrinol, 2011, 164:303-307. doi: 10.1530/EJE-10-0833
[46]	Borodic G, Hinkle DM, Cia Y. Drug-induced graves disease from CTLA-4 receptor suppression. Ophthalmic Plast Reconstr Surg[J]. Ophthalmic Plast Reconstr Surg, 2011, 27:e87-e88. doi: 10.1097/IOP.0b013e3181ef72a1
[47]	McElnea E, Ní Mhéalóid A, Moran S, et al. Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab[J]. Orbit, 2014, 33:424-427. doi: 10.3109/01676830.2014.949792
[48]	Park ESY, Rabinowits G, Hamnvik OR, et al. A case of Graves' ophthalmopathy associated with pembrolizumab (Keytruda) therapy[J]. J AAPOS, 2018, 22:310-312. doi: 10.1016/j.jaapos.2018.01.006
[49]	Campredon P, Imbert P, Mouly C, et al. Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment[J]. Eur Thyroid J, 2018, 7:84-87. doi: 10.1159/000485742
[50]	Hudzik B, Zubelewicz-Szkodzinska B. Radiocontrast-induced thyroid dysfunction: is it common and what should we do about it?[J]. Clin Endocrinol (Oxf), 2014, 80:322-327. doi: 10.1111/cen.12376
[51]	Thompson JA, Schneider BJ, Brahmer J, et al. NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020[J].J Natl Compr Canc Netw, 2020, 18:230-241. doi: 10.6004/jnccn.2020.0012
[52]	Peiró I, Palmero R, Iglesias P, et al.Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes[J]. Endocrine, 2019, 64:605-613. doi: 10.1007/s12020-019-01871-7
[53]	Borodic GE, Hinkle D.Ipilimumab-induced orbital inflamma-tion resembling Graves disease with subsequent development of systemic hyperthyroidism from CTLA-4 receptor suppression[J]. Ophthalmic Plast Reconstr Surg, 2014, 30:83. http://www.ncbi.nlm.nih.gov/pubmed/24398505
[54]	Yu C, Chopra IJ, Ha E.A novel melanoma therapy stirs up a storm: ipilimumab-induced thyrotoxicosis[J]. Endocrinol Diabetes Metab Case Rep, 2015:140092. http://pubmedcentralcanada.ca/pmcc/articles/PMC4330494/?lang=fr
[55]	Yonezaki K, Kobayashi T, Imachi H, et al. Combination therapy of ipilimumab and nivolumab induced thyroid storm in a patient with Hashimoto's disease and diabetes mellitus: a case report[J]. J Med Case Rep, 2018, 12:171. doi: 10.1186/s13256-018-1708-x
[56]	McMillen B, Dhillon MS, Yong-Yow S. A rare case of thyroid storm[J]. BMJ Case Rep, 2016: 10.1136/bcr-2016-214603.

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 663
HTML全文浏览量: 140
PDF下载量: 43
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

地址：	北京市东城区帅府园1号北京协和医院老楼7号楼 3层302室《协和医学杂志》编辑部
电话：	010-69154261/4262
E - mail：	medj@pumch.cn mjpumch@126.com
期刊网站版权所有：	《协和医学杂志》编辑部京ICP备 11002662

留言板

免疫检查点抑制剂相关甲状腺毒症

doi: 10.3969/j.issn.1674-9081.2020.00.004

通讯作者:
李乃适电话：010-69155073, E-mail：LNS@medmail.com.cn

计量

Thyrotoxicosis Related to Immune Checkpoint Inhibitors

Corresponding author: LI Nai-shi Tel: 86-10-69155073, E-mail: LNS@medmail.com.cn

计量

目录

留言板

免疫检查点抑制剂相关甲状腺毒症

doi: 10.3969/j.issn.1674-9081.2020.00.004

通讯作者: 李乃适 电话：010-69155073, E-mail：LNS@medmail.com.cn

计量

出版历程

Thyrotoxicosis Related to Immune Checkpoint Inhibitors

Corresponding author: LI Nai-shi Tel: 86-10-69155073, E-mail: LNS@medmail.com.cn

计量

出版历程

目录

通讯作者:
李乃适电话：010-69155073, E-mail：LNS@medmail.com.cn