Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms
Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms
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DOI：
10.1055/s-0042-119528
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发表时间：
2017-04-01
影响因子：
1.8
通讯作者：
Samantray, J.
中科院分区：
文献类型：
--
作者：
Alhusseini, M.;Samantray, J.
背景资料：据报道，使用针对细胞毒性T淋巴细胞相关抗原4（CTLA-4）和程序性细胞死亡1受体（PD-1）的单克隆抗体对各种癌症进行免疫治疗会导致甲状腺功能障碍。然而，人们对潜在的致病机制和随后发生的甲状腺功能减退症的过程知之甚少。在这份报告中，我们使用的甲状腺球蛋白和甲状腺抗体水平的变化，在免疫治疗谁发展甲状腺功能减退症的患者，以更好地了解其发病机制，以及检查甲状腺功能减退症的状态，在长期的。方法：我们报告了一个病例系列的10例患者谁发展甲状腺功能减退症后开始免疫治疗（无论是抗PD-1单独或与抗CTLA-4）。在初始甲状腺炎阶段以及甲状腺功能减退阶段，观察到可用的甲状腺抗体，包括抗甲状腺球蛋白（抗Tg）、抗甲状腺过氧化物酶（抗TPO）和甲状腺刺激免疫球蛋白（TSI）。在6个月时观察到甲状腺功能减退的持续或缓解。总结：在甲状腺炎阶段，50%的患者Tg滴度升高，40%的患者抗Tg升高，40%的患者TSI升高。所有这些滴度在甲状腺功能减退期均降低。80%的病例出现永久性甲减。结论：免疫治疗后甲减的发生有免疫和非免疫介导的机制，可能是持续性的。
Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term.Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months.Summary: During the thyroiditis phase, 50 % of the patients had elevated Tg titers, 40 % had elevated anti-Tg, and 40 % had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80 % of the cases.Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent.