Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei, 071000, China.
Department of Endocrinology, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, China.
Endocr Metab Immune Disord Drug Targets. 2024;24(10):1169-1179. doi: 10.2174/1871530323666230821102730.
BACKGROUND: The present recommendations, consensus, or guidelines for the replacement dosage for hypothyroidism induced by programmed cell death protein 1 (PD-1) therapy are not uniform, and there are very few special clinical trials that have examined the replacement dosage for it. OBJECTIVES: This article illustrates the clinical characteristics of hypothyroidism induced by PD-1 antibodies (Abs) and reports the recommended replacement dosage for hypothyroidism. METHODS: Eighteen patients with overt primary hypothyroidism induced by PD-1 Abs (group 1) were selected from 655 patients with different tumor types. Retrospective analysis was performed on patients in group 1 and 18 patients with natural courses of overt primary hypothyroidism who were age- and sex-matched with the patients in group 1 (group 2). The replacement dosages required for the patients in the two groups were compared. RESULTS: Thyroid dysfunction occurred in group 1 after approximately 3.0 ± 1.4 cycles of PD-1 therapy (1-6 stages), with a median time of 61.5 days. The median time of onset of hypothyroidism among all patients was 87.5 days (30-240 days). Most of the patients with hypothyroidism were asymptomatic, and the onset of hypothyroidism was independent of age, sex, TPOAb, TgAb and TSH in group 1 (P>0.05). The average replacement dosage for patients in group 1 was 1.8 ± 0.6 μg/kg/d (0.6-3.2 μg/kg/d). Multiple linear regression analysis showed that sex, age, TPOAb, TgAb and TSH were not correlated with drug dosage. CONCLUSION: It seemed that the average maintenance dosage of levothyroxine might need to be 1.8 μg/kg/day for patients with overt hypothyroidism induced by PD-1 Abs.
背景:程序性细胞死亡蛋白 1(PD-1)治疗诱导的甲状腺功能减退症的替代剂量的建议、共识或指南并不统一,很少有专门的临床试验来检查其替代剂量。
目的:本文阐述了 PD-1 抗体诱导的甲状腺功能减退症的临床特征,并报告了甲状腺功能减退症的推荐替代剂量。
方法:从 655 例不同肿瘤类型的患者中选择 18 例 PD-1 抗体(Abs)诱导的显性原发性甲状腺功能减退症患者(组 1)。对组 1 患者和与组 1 患者年龄和性别匹配的 18 例自然病程的显性原发性甲状腺功能减退症患者(组 2)进行回顾性分析。比较两组患者的替代剂量需求。
结果:组 1 患者在接受约 3.0±1.4 个周期的 PD-1 治疗(1-6 个阶段)后出现甲状腺功能障碍,中位时间为 61.5 天。所有患者甲状腺功能减退症的中位发病时间为 87.5 天(30-240 天)。大多数甲状腺功能减退症患者无症状,且组 1 患者甲状腺功能减退症的发病与年龄、性别、TPOAb、TgAb 和 TSH 无关(P>0.05)。组 1 患者的平均替代剂量为 1.8±0.6μg/kg/d(0.6-3.2μg/kg/d)。多元线性回归分析显示,性别、年龄、TPOAb、TgAb 和 TSH 与药物剂量无关。
结论:PD-1 Abs 诱导的显性甲状腺功能减退症患者的左旋甲状腺素维持剂量可能需要 1.8μg/kg/天。
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