Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States.
Department of Family and Social Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States.
Front Endocrinol (Lausanne). 2023 Apr 19;14:1169173. doi: 10.3389/fendo.2023.1169173. eCollection 2023.
Immune-related endocrinopathies are common after immune checkpoint inhibitor (ICI) therapy, among which destructive thyroiditis is the most prevalent. Improved survival outcomes have been associated with immune-related adverse events. We aimed to compare the clinical course and biochemical parameters of two subtypes of ICI-related destructive thyroiditis: a transient thyrotoxicosis that reverts to either euthyroidism (TT; transient thyroiditis) versus progression to permanent hypothyroidism (PH), and to identify prognostic markers in cancer patients receiving ICI therapy who developed DT.
This retrospective observational study included 124 patients who developed a transient thyrotoxicosis due to a destructive thyroiditis after ICI therapy from January 1, 2016 to April 30, 2021 at the Montefiore Medical Center. Patients were categorized as either TT or PH based on spontaneous renormalization of the TSH or the permanent need for thyroid hormone replacement, respectively. Thyroid hormone and antibody levels, serum inflammatory markers, eosinophils, and metabolic uptake of the thyroid on PET imaging, each corresponding closest to a suppressed TSH, were characterized. Survival from TT and PH were also analyzed.
Of the 124 patients, 53 developed PH and 71 developed TT. The PH group developed thyrotoxicosis at a median of 42 days from the first ICI dose while the TT group took significantly longer at 56 days. Thyroidal PET uptake was increased in 18.9% of the PH group versus 6.0% of the TT group (P=0.04). Three different survival models consistently demonstrated a trend towards increased survival in the PH group, compared to the TT group.
Our results suggest that PH developing after ICI-induced destructive thyroiditis may be associated with a more robust inflammatory and antitumor response to ICI therapy. The results suggests that PH may be a potential clinical predictor of improved survival.
免疫检查点抑制剂（ICI）治疗后常发生免疫相关内分泌疾病，其中破坏性甲状腺炎最为常见。改善生存结果与免疫相关不良事件有关。我们旨在比较两种 ICI 相关破坏性甲状腺炎的临床过程和生化参数：一种是恢复至甲状腺功能正常（TT；一过性甲状腺炎）的一过性甲状腺毒症，另一种是进展为永久性甲状腺功能减退（PH），并确定接受 ICI 治疗的癌症患者发生 DT 的预后标志物。
这项回顾性观察研究纳入了 2016 年 1 月 1 日至 2021 年 4 月 30 日期间在 Montefiore 医疗中心因 ICI 治疗后发生破坏性甲状腺炎而出现一过性甲状腺毒症的 124 例患者。根据 TSH 自发性恢复或永久性甲状腺激素替代的需要，将患者分为 TT 或 PH 组。对甲状腺激素和抗体水平、血清炎症标志物、嗜酸性粒细胞以及甲状腺 PET 成像的代谢摄取进行了特征描述，这些描述分别对应于抑制 TSH 时的情况。还分析了 TT 和 PH 的生存情况。
124 例患者中，53 例发展为 PH，71 例发展为 TT。PH 组在首次 ICI 剂量后中位 42 天出现甲状腺毒症，而 TT 组需要更长时间，为 56 天。PH 组甲状腺 PET 摄取增加的比例为 18.9%，而 TT 组为 6.0%（P=0.04）。三种不同的生存模型均一致表明，与 TT 组相比，PH 组的生存趋势更好。
我们的结果表明，ICI 诱导的破坏性甲状腺炎后发生 PH 可能与对 ICI 治疗的更强烈炎症和抗肿瘤反应有关。结果表明，PH 可能是改善生存的潜在临床预测指标。
