Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, Illinois, USA.
Department of Family & Preventative Medicine, Rush University Medical Centers, Chicago, Illinois, USA.
Thyroid. 2024 Oct;34(10):1205-1213. doi: 10.1089/thy.2024.0358. Epub 2024 Sep 18.
Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; value = 0.006; mean working memory scores: 6.8 vs 6.4; value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms.
接受左甲状腺素（LT4）单药治疗的甲状腺功能减退症患者，尽管促甲状腺激素（TSH）水平正常，但仍可能存在持续的甲状腺功能减退症症状，包括认知症状。目前尚不清楚 LT4 单药治疗是否足以随着时间的推移使认知功能结果正常化。这是一项在美国 7 个研究地点的多个研究中心进行的、代表 5 个族裔/种族群体的中年女性的多站点纵向研究，该研究纳入了来自全美各地的妇女，参加了妇女健康全国研究。对这些女性进行了甲状腺疾病史和 LT4 使用情况的筛查。该研究包括两个主要组：接受 LT4 治疗的甲状腺功能减退症妇女和没有甲状腺疾病的对照组妇女。每位参与者在研究期间完成了最多 9 次认知评估，测试了处理速度、工作记忆和情景记忆（即时和延迟回忆）。为了确定 LT4 治疗的甲状腺功能减退症与认知功能轨迹之间的关系，对每个认知评估的评分进行了多变量广义线性混合模型分析。协变量包括社会人口统计学、临床特征和绝经状态（早/绝经前期、晚绝经前期和手术/绝经后期）。进行了敏感性分析，以评估异常 TSH 水平和练习效应（即重复测试后评分提高）的影响。在纳入研究的 2033 名女性中，有 227 名（11.2%）符合 LT4 治疗的甲状腺功能减退症标准。在基线时，LT4 治疗的女性处理速度和工作记忆评分更高（平均处理速度评分：56.5 对 54.4； 值=0.006；平均工作记忆评分：6.8 对 6.4； 值=0.018）。然而，当考虑 LT4 治疗的甲状腺功能减退症随时间的影响时，在不调整协变量的情况下，甲状腺功能减退症组和对照组之间的认知下降率（任何测量）没有显著差异。当考虑 TSH 水平异常的 LT4 治疗女性或最小化练习效应后，结果相似。我们观察到 LT4 治疗的甲状腺功能减退症女性与无甲状腺疾病的女性之间认知衰退无差异。对于有认知症状的相似年龄患者，如果甲状腺功能检测正常，临床医生应考虑除甲状腺激素治疗不足以外的其他原因来解释这些症状。
