Xu Huaijin, Liu Hongzhou, Hu Xiaodong, Jia Xiaomeng, Xue Zhe, Wang Anning, Kang Shaoyang, Lyu Zhaohui
School of Medicine, Nankai University, Tianjin, China.
Department of Endocrinology, First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Front Endocrinol (Lausanne). 2025 Jun 4;16:1595002. doi: 10.3389/fendo.2025.1595002. eCollection 2025.
The inconclusive associations between thyroid-related hormones and differentiated thyroid cancer (DTC) suggest complex pathophysiologic processes, for which thyroid hormone sensitivity may provide new insights.
We retrospectively analyzed preoperative clinical data and postoperative pathological data of 9,515 euthyroid adults who underwent thyroidectomy for thyroid nodules pathologically confirmed as benign nodules or DTC. Composite thyroid parameters were calculated, including TSH index (TSHI), thyrotroph thyroxine resistance index (TT4RI), FT3/FT4 ratio (FT3/FT4) and the thyroid's secretory capacity (SPINA-GT).
Increased TSHI (OR=1.34, 95%CI: 1.27-1.41) and TT4RI (OR=1.35, 95%CI: 1.28-1.42) reflecting reduced central thyroid hormone sensitivity, decreased FT3/FT4 (OR=0.81, 95%CI: 0.77-0.86) reflecting reduced peripheral thyroid hormone sensitivity, and decreased SPINA-GT (OR=0.78, 95%CI: 0.74-0.82) were associated with DTC after adjustment for confounders. The contributions of thyroid hormone sensitivity indices remained in subgroups stratified by age, sex, metabolic factors, thyroid autoimmunity status, and nodule size. A non-linear relationship between thyroid hormone sensitivity indices and probability of DTC was observed. The association of DTC with TT4RI or TSHI was stronger than with other thyroid parameters such as TSH (thyroid stimulating hormone). ROC analysis for the distinction between DTC and benign disease showed no single thyroid parameter with the coexistence of high sensitivity and specificity.
Reduced central and peripheral sensitivity to thyroid hormones is associated with DTC in the euthyroid thyroidectomy population and provides additional information on the odds of malignancy in thyroid nodules at risk for surgery, warranting consideration of the role of sensitivity to thyroid hormones in mechanisms and prediction models for DTC.
甲状腺相关激素与分化型甲状腺癌（DTC）之间不确定的关联提示了复杂的病理生理过程，甲状腺激素敏感性可能为其提供新的见解。
我们回顾性分析了9515例甲状腺功能正常的成年人的术前临床数据和术后病理数据，这些患者因甲状腺结节接受了甲状腺切除术，术后病理证实为良性结节或DTC。计算了综合甲状腺参数，包括促甲状腺激素指数（TSHI）、促甲状腺素甲状腺素抵抗指数（TT4RI）、游离三碘甲状腺原氨酸/游离甲状腺素比值（FT3/FT4）和甲状腺分泌能力（SPINA-GT）。
反映中枢甲状腺激素敏感性降低的TSHI升高（OR=1.34，95%CI：1.27-1.41）和TT4RI升高（OR=1.35，95%CI：1.28-1.42），反映外周甲状腺激素敏感性降低的FT3/FT4降低（OR=0.81，95%CI：0.77-0.86），以及SPINA-GT降低（OR=0.78，95%CI：0.74-0.82）在调整混杂因素后与DTC相关。甲状腺激素敏感性指数的作用在按年龄、性别、代谢因素、甲状腺自身免疫状态和结节大小分层的亚组中仍然存在。观察到甲状腺激素敏感性指数与DTC概率之间存在非线性关系。DTC与TT4RI或TSHI的关联强于与其他甲状腺参数如促甲状腺激素（TSH）的关联。区分DTC和良性疾病的ROC分析显示，没有单一的甲状腺参数同时具有高敏感性和特异性。
在甲状腺功能正常的甲状腺切除人群中，中枢和外周对甲状腺激素的敏感性降低与DTC相关，并为有手术风险的甲状腺结节的恶性几率提供了额外信息，有必要考虑甲状腺激素敏感性在DTC的机制和预测模型中的作用。
