de Filette Jeroen, Jansen Yanina, Schreuer Max, Everaert Hendrik, Velkeniers Brigitte, Neyns Bart, Bravenboer Bert
Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
J Clin Endocrinol Metab. 2016 Nov;101(11):4431-4439. doi: 10.1210/jc.2016-2300. Epub 2016 Aug 29.
Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized.
To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction.
Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis.
Ninety-nine patients with advanced melanoma (age, 26.3-93.6 years; 63.6% females) who received at least one administration of pembrolizumab.
Patient characteristics, thyroid function (TSH, free T), thyroid autoantibodies, and FDG-PET/CT.
Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism.
Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates.
免疫检查点阻断与内分泌相关不良事件有关。帕博利珠单抗（一种抗程序性细胞死亡蛋白1（PD-1）受体单克隆抗体）治疗期间的甲状腺功能障碍仍有待充分阐明。
评估帕博利珠单抗相关甲状腺功能障碍的发生率和特征。
在一家转诊肿瘤中心的扩大准入项目中，对开始使用帕博利珠单抗的黑色素瘤患者进行前瞻性甲状腺功能监测。对符合亚急性甲状腺炎的病例，回顾正电子发射断层扫描/计算机断层扫描（FDG-PET/CT）上的氟脱氧葡萄糖摄取情况。
99例晚期黑色素瘤患者（年龄26.3 - 93.6岁；63.6%为女性），接受了至少一次帕博利珠单抗治疗。
患者特征、甲状腺功能（促甲状腺激素、游离甲状腺素）、甲状腺自身抗体及FDG-PET/CT。
17例患者出现18次甲状腺功能障碍不良事件。12例患者发生甲状腺毒症，其中9例进展为甲状腺功能减退。6例患者出现单纯性甲状腺功能减退。15例甲状腺功能减退患者中有10例需要左甲状腺素治疗。10例病例中有4例在甲状腺功能障碍期间甲状腺自身抗体升高。在所有7例进展为甲状腺功能减退的甲状腺毒症患者中，均观察到甲状腺弥漫性FDG摄取增加。
帕博利珠单抗治疗的黑色素瘤患者中甲状腺功能障碍很常见。与亚急性甲状腺炎相关的甲状腺功能减退和甲状腺毒症是最常见的表现形式。在抗PD-1单克隆抗体治疗期间，建议进行系列甲状腺功能检查。与亚急性甲状腺炎相符的甲状腺毒症与甲状腺弥漫性FDG摄取增加有关。甲状腺自身抗体的前瞻性作用以及组织病理学相关性应进一步研究。
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