Department of Internal Medicine, Ito Hospital, Shibuya, Japan.
Department of Social Epidemiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Thyroid. 2022 Oct;32(10):1243-1248. doi: 10.1089/thy.2022.0252. Epub 2022 Sep 28.
The severity of hyperthyroidism in Graves' disease (GD) has been reported to be worse in younger patients and to gradually improve with advancing age, accompanied by declining thyrotropin (TSH) receptor antibody (TRAb) values. This study was conducted to explore the extent to which the declining TRAb production may contribute to a decrease in severe hyperthyroidism with advancing age in patients with GD. This study was a cross-sectional analysis of retrospectively reviewed data. The medical records of patients newly diagnosed with GD at Ito Hospital, between January 2005 and June 2019, were examined. Patients were divided into age-stratified groups for evaluation. Multivariable logistic regression was performed to estimate the odds ratio (OR) of severe hyperthyroidism by increasing age. Mediation analyses were also conducted to quantify the association between age and declining severity of hyperthyroidism mediated through decreased TRAb productivity. A total of 21,018 patients with newly diagnosed GD (3848 male and 17,170 female) were included. A correlation was observed between TRAb value and thyroid hormone values in each age-stratified group, which became weaker with an increase in age. Patients aged <40 years had a higher risk of severe hyperthyroidism (free thyroxine [fT4] level >7.0 ng/dL [ = 5616], OR [confidence interval, CI] = 1.80 [1.68-1.92]; free triiodothyronine [fT3] level >25 pg/mL [ = 4501], OR [CI] = 2.06 [1.92-2.23]) than those aged ≧40 years. In examining the relationship between age and severe hyperthyroidism, the proportion mediated through TRAb productivity was 8.5% and 8.4% using fT4 and fT3 as an outcome index, respectively. Declining TRAb value mediated only 8.5% of the negative association between age and severity of hyperthyroidism. The presence of other underlying mechanisms, such as the decline in the reactivity of thyrocytes to TSH stimulation, requires further investigation.
格雷夫斯病（GD）的甲状腺功能亢进症的严重程度据报道在年轻患者中更为严重，并且随着年龄的增长逐渐改善，同时促甲状腺激素（TSH）受体抗体（TRAb）值下降。本研究旨在探讨 TRAb 产生的下降在多大程度上导致 GD 患者随着年龄的增长，严重甲状腺功能亢进症的减少。本研究是对 Ito 医院 2005 年 1 月至 2019 年 6 月期间新诊断为 GD 的患者回顾性数据的横断面分析。检查了患者的病历。将患者分为年龄分层组进行评估。采用多变量逻辑回归估计年龄增加时严重甲状腺功能亢进症的优势比（OR）。还进行了中介分析，以量化年龄与 TRAb 生产力下降导致的甲状腺功能亢进严重程度下降之间的关联。共纳入 21018 例新诊断为 GD 的患者（男 3848 例，女 17170 例）。在每个年龄分层组中观察到 TRAb 值与甲状腺激素值之间存在相关性，随着年龄的增长相关性减弱。年龄<40 岁的患者发生严重甲状腺功能亢进症（游离甲状腺素[fT4]水平>7.0ng/dL[=5616]，OR[置信区间，CI]为 1.80[1.68-1.92]；游离三碘甲状腺原氨酸[fT3]水平>25pg/mL[=4501]，OR[CI]为 2.06[1.92-2.23]）的风险高于年龄≧40 岁的患者。在检查年龄与严重甲状腺功能亢进症之间的关系时，使用 fT4 和 fT3 作为结局指标，TRAb 产量介导的比例分别为 8.5%和 8.4%。TRAb 值的下降仅介导了年龄与甲状腺功能亢进症严重程度之间负相关的 8.5%。需要进一步研究其他潜在机制，如甲状腺细胞对 TSH 刺激反应性的下降。
