Background: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. Methods: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. Results: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3–32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%,p< 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4–98.0), kappa 0.83. Conclusion: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.
背景：用于免疫检查点抑制剂（ICI）疗效评估的FDG-PET/CT可偶然识别免疫相关不良事件（irAEs），包括甲状腺炎。本研究旨在探讨FDG-PET/CT显示的甲状腺炎证据与甲状腺功能障碍临床及生化演变过程的时间关联性。方法：由两位独立的盲态核医学医师对127例晚期黑色素瘤患者进行回顾性分析，这些患者在2016年1月至2019年1月期间接受联合ICI治疗，并在基线期和治疗监测期间接受PET/CT检查，评估甲状腺FDG摄取情况。采用甲状腺功能检测（TFTs）作为金标准，通过受试者工作特征（ROC）曲线评估观察者间一致性并确定FDG-PET/CT的诊断效能。连续记录甲状腺最大标准化摄取值（SUVmax）及其随时间变化与纵向生化指标的关系。结果：在开始ICI治疗后中位时间3周，43/127例（34%）患者通过异常TFTs确诊甲状腺炎。FDG-PET/CT检查在基线期及治疗后中位时间11周（范围3-32周）进行。ROC分析显示FDG-PET/CT检测甲状腺炎的曲线下面积为0.87（95% CI 0.80-0.94），阳性预测值为93%。在具有生化证据的甲状腺炎患者中，FDG-PET/CT阳性者更易发展为显性甲状腺功能减退症（77% vs 35%，p<0.01）。在指标测试评估中，核医学医师间的观察者一致性达到近乎完美的93.7%（95% CI 89.4-98.0），kappa值为0.83。结论：在接受ICI治疗的患者中，常规FDG-PET/CT检查发现的甲状腺代谢活性增高通常晚于常规生化诊断。甲状腺FDG摄取升高可预测显性临床甲状腺功能减退，提示初始甲状腺毒症期后持续存在的强烈炎症反应可能预示着甲状腺组织的破坏。
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