Induction of Painless Thyroiditis in Patients Receiving Programmed Death 1 Receptor Immunotherapy for Metastatic Malignancies
Induction of Painless Thyroiditis in Patients Receiving Programmed Death 1 Receptor Immunotherapy for Metastatic Malignancies
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DOI：
10.1210/jc.2014-4560
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发表时间：
2015-05-01
影响因子：
5.8
通讯作者：
Walfish, Paul G.
中科院分区：
文献类型：
--
作者：
Orlov, Steven;Salari, Farnaz;Walfish, Paul G.
内容：针对抑制T细胞活化的免疫检查点[细胞毒性T淋巴细胞抗原4（CTLA-4）和程序性细胞死亡1（PD-1）]的免疫疗法是几种转移性恶性肿瘤的新兴且有前景的治疗。然而，这些疗法对甲状腺功能的确切不良影响尚未得到很好的描述。病例描述：我们报告10例无痛性甲状腺炎综合征（PTS）从一个新的病因，免疫治疗与抗PD-1单克隆抗体（mAb）在治疗转移性恶性肿瘤。6例患者出现短暂性甲状腺毒症，其中促甲状腺素结合抑制性免疫球蛋白（TBII）均不存在，而4例患者有阳性抗甲状腺抗体的证据。所有甲状腺功能亢进患者均需要暂时性β受体阻滞剂治疗，并且甲状腺功能亢进症自发消退，随后出现甲状腺功能减退症。4例患者出现甲状腺功能减退症，但未检测到先前的甲状腺毒性阶段，发生在首次药物暴露后6-8周。所有这些患者的抗甲状腺抗体均呈阳性，需要至少6个月的甲状腺激素替代治疗。结论：应监测接受抗PD-1 mAb治疗的患者是否有PTS的体征和症状，这些体征和症状可能需要β受体阻滞剂或甲状腺激素替代治疗的支持性治疗。抗PD-1 mAb是PTS的一种新型外源性病因，为可能调节内源性PTS（包括散发性和产后甲状腺炎病例）发生的免疫网络可能扰动提供了新的见解。
Context: Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described.Case Description: We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months.Conclusions: Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.