Reduced sensitivity to thyroid hormones is associated with differentiated thyroid cancer in the euthyroid thyroidectomy population.

IF 3.9 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Frontiers in Endocrinology Pub Date : 2025-06-04 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1595002

Huaijin Xu, Hongzhou Liu, Xiaodong Hu, Xiaomeng Jia, Zhe Xue, Anning Wang, Shaoyang Kang, Zhaohui Lyu

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Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

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甲状腺激素敏感性降低与甲状腺癌分化有关。

背景：甲状腺相关激素与分化型甲状腺癌（DTC）之间的关系尚不明确，提示其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。方法：回顾性分析9,515例甲状腺功能正常的成人因甲状腺结节行甲状腺切除术的术前临床资料和术后病理资料，病理证实为良性结节或DTC。计算甲状腺综合参数，包括TSH指数（TSHI）、促甲状腺素抵抗指数（TT4RI）、FT3/FT4比值（FT3/FT4）和甲状腺分泌能力（SPINA-GT）。结果：调整混杂因素后，TSHI （OR=1.34, 95%CI: 1.27-1.41）和TT4RI （OR=1.35, 95%CI: 1.28-1.42）升高反映中枢甲状腺激素敏感性降低，FT3/FT4降低（OR=0.81, 95%CI: 0.77-0.86）反映外周甲状腺激素敏感性降低，SPINA-GT降低（OR=0.78, 95%CI: 0.74-0.82）与DTC相关。甲状腺激素敏感性指数的贡献仍然是按年龄、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。甲状腺激素敏感性指标与DTC发生概率呈非线性关系。与TSH（促甲状腺激素）等其他甲状腺参数相比，DTC与TT4RI或TSHI的相关性更强。对DTC与良性疾病的区分进行ROC分析，发现甲状腺参数没有单一，具有较高的敏感性和特异性。结论：在甲状腺功能正常的甲状腺切除术人群中，中枢和外周甲状腺激素敏感性降低与DTC相关，并提供了甲状腺结节手术风险中恶性肿瘤几率的额外信息，值得考虑甲状腺激素敏感性在DTC机制和预测模型中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

5.70

自引率

9.60%

发文量

3023

审稿时长

14 weeks

期刊介绍： Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.