Two distinct clinical patterns of checkpoint inhibitor-induced thyroid dysfunction
Two distinct clinical patterns of checkpoint inhibitor-induced thyroid dysfunction
复制标题
DOI：
10.1530/ec-19-0473
复制
发表时间：
2020-04-01
影响因子：
2.9
通讯作者：
Pirmohamed, Munir
中科院分区：
文献类型：
--
作者：
Olsson-Brown, Anna;Lord, Rosemary;Pirmohamed, Munir
简介：免疫检查点抑制剂可导致甲状腺功能障碍。然而，在现实世界的人群中ICI诱导的甲状腺功能障碍的临床表型的理解是有限的。本研究的目的是为了验证功能障碍的临床模式，并评估与此患者cohol.Materials和方法相关的人口统计学，生化和免疫学特征：要验证从一个单一的，英国区域癌症中心的患者甲状腺功能障碍的纵向临床过程中，进行了回顾性分析。入选标准包括所有接受抗PD-1检查点抑制剂（ICI）治疗的患者，无论是单药治疗（派姆单抗/纳武单抗）还是与CTLA-4抑制剂（伊匹单抗）联合治疗。毒性的模式进行了评估，连同抗体titres.Results的评估：在16个月，甲状腺功能障碍被认为是在13/90和3/13的患者与抗PD 1单药治疗，并与ipilimumab相结合，分别。患者发生甲状腺功能亢进，随后发生甲状腺功能减退（12/16）或新发甲状腺功能减退（4/16）。大多数患者为女性（n = 11）。所有患者均需要甲状腺替代治疗。甲状腺功能障碍的临床模式和甲状腺自身抗体的存在之间没有关系。结论：ICI治疗的患者甲状腺功能障碍有两种不同的模式。甲状腺炎患者在绝大多数情况下发展为继发性甲状腺功能减退症。类固醇或其他治疗方法对甲亢期的潜在益处尚不清楚。通过适当的监测早期发现这些患者将改善临床管理和早期激素替代治疗，减少甲状腺功能减退症的症状负担。
Introduction: Immune checkpoint inhibitors can lead to thyroid dysfunction. However, the understanding of the clinical phenotype of ICI-induced thyroid dysfunction in the real-world population is limited. The purpose of this study was to characterise the clinical patterns of dysfunction and evaluate the demographic, biochemical and immunological features associated with this patient cohort.Materials and methods: To characterise the longitudinal clinical course of thyroid dysfunction in patients from a single, UK regional cancer centre, a retrospective review of patients was conducted. Inclusion criteria included all patients treated with antiPD-1 checkpoint inhibitors (ICI), either as monotherapy (pembrolizumab/nivolumab) or in combination with a CTLA-4 inhibitor (ipilimumab). Patterns of toxicity were evaluated together with assessment of antibody titres.Results: Over 16 months, thyroid dysfunction was seen in 13/90 and 3/13 patients treated with anti-PD1 monotherapy and in combination with ipilimumab, respectively. Patients either developed hyperthyroidism followed by hypothyroidism (12/16) or de novo hypothyroidism (4/16). Most patients were female (n = 11). All patients required thyroid replacement therapy. There was no relationship between clinical pattern of dysfunction and the presence of thyroid autoantibodies.Conclusions: There are two distinct patterns of thyroid dysfunction in ICI-treated patients. Patients with thyroiditis develop subsequent hypothyroidism in the vast majority of cases. The potential benefit from steroids or other therapy to manage the hyperthyroid phase remains unclear. Early detection of these patients through appropriate monitoring will improve clinical management and early hormone replacement, reducing the symptomatic burden of hypothyroidism.