O'Malley Grenye, Lee Hanna J, Parekh Samir, Galsky Matthew D, Smith Cardinale B, Friedlander Philip, Yanagisawa Robert T, Gallagher Emily J
Endocr Pract. 2017 Oct;23(10):1223-1231. doi: 10.4158/EP171832.OR.
To describe the evolution of thyroid dysfunction in a series of patients with cancer treated with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) monoclonal antibody, nivolumab.
Cases of thyroid dysfunction after initiation of checkpoint inhibitor treatment were identified from the Division of Endocrinology clinical practice at Mount Sinai Hospital, New York from April 2016 to February 2017. Charts were reviewed to identify patients treated with nivolumab with new onset of thyroid dysfunction.
Nine cases of thyroid function in patients who were treated with nivolumab were identified. There were 4 male and 5 female patients, with a mean age of 66 years (range 50-76 years). Seven patients ultimately developed hypothyroidism. Five of the 7 patients developed abnormal thyroid function tests within the first 90 days of starting therapy (range 21-84 days), 3 of whom had transient hyperthyroidism. Transient hyperthyroidism evolved rapidly to hypothyroidism; elevated thyroid-stimulating hormone (TSH) levels were detected within 16 to 32 days of the last documented low TSH. In the 2 patients without a hyperthyroid phase, TSH levels >50 were found 18 to 28 days after the last normal TSH value.
As the use of immune checkpoint inhibitor therapy increases, the need for prompt diagnosis and treatment of drug-induced thyroid disease will become more important. As illustrated in this case series, in contrast to other causes of auto-immune thyroiditis, hypothyroidism can develop rapidly within 3 months of treatment. Close monitoring is necessary to detect the development of thyroid dysfunction and avoid preventable morbidity.
Anti-TPO Abs = anti-thyroglobulin antibodies; CT = computed tomography; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; FDA = U.S. Food & Drug Administration; FDG-PET = fluorodeoxyglucose-positron emission tomography; PD-1 = programmed cell death protein-1; PD-L1 = programmed death-ligand 1; T3 = triiodothyronine; T4 = thyroxine; TG = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone.
描述接受免疫检查点抑制剂抗程序性细胞死亡蛋白1（PD-1）单克隆抗体纳武单抗治疗的一系列癌症患者中甲状腺功能障碍的演变情况。
从2016年4月至2017年2月纽约西奈山医院内分泌科临床实践中确定检查点抑制剂治疗开始后出现甲状腺功能障碍的病例。查阅病历以确定接受纳武单抗治疗且新发甲状腺功能障碍的患者。
确定了9例接受纳武单抗治疗患者的甲状腺功能情况。有4例男性和5例女性患者，平均年龄66岁（范围50 - 76岁）。7例患者最终发展为甲状腺功能减退。7例患者中有5例在开始治疗的前90天内（范围21 - 84天）甲状腺功能检查出现异常，其中3例有短暂性甲状腺功能亢进。短暂性甲状腺功能亢进迅速演变为甲状腺功能减退；在最后记录的低促甲状腺激素（TSH）水平后的16至32天内检测到TSH水平升高。在没有甲状腺功能亢进阶段的2例患者中，在最后一次正常TSH值后的18至28天发现TSH水平>50。
随着免疫检查点抑制剂治疗的使用增加，及时诊断和治疗药物性甲状腺疾病的需求将变得更加重要。如本病例系列所示，与自身免疫性甲状腺炎的其他病因相比，甲状腺功能减退可在治疗后3个月内迅速发展。密切监测对于检测甲状腺功能障碍的发生并避免可预防的发病至关重要。
Anti-TPO Abs = 抗甲状腺球蛋白抗体；CT = 计算机断层扫描；CTLA-4 = 细胞毒性T淋巴细胞相关蛋白4；FDA = 美国食品药品监督管理局；FDG-PET = 氟脱氧葡萄糖正电子发射断层扫描；PD-1 = 程序性细胞死亡蛋白1；PD-L1 = 程序性死亡配体1；T3 = 三碘甲状腺原氨酸；T4 = 甲状腺素；TG = 甲状腺球蛋白；TPO = 甲状腺过氧化物酶；TSH = 促甲状腺激素
