Subclinical Hypothyroidism: Mood, Cognition and the effect of L-thyroxine treatme

描述(申请人提供)：亚临床甲状腺功能减退症是一种生化诊断，其特征是促甲状腺激素(TSH)水平升高，而循环甲状腺激素(T4)和三碘甲状腺原氨酸(T3)水平正常。虽然SCH不存在临床甲状腺功能减退的症状，但它可能与情绪、认知和身体症状有关，并增加了高脂血症和缺血性心脏病的风险。SCH还可能增加抑郁、认知障碍和痴呆症的易感性。SCH相对常见，发生在大约5%至10%的人口中，60岁以上的女性患病率较高(高达20%)。到目前为止，还没有设计良好的对照研究来评估SCH对最脆弱的人群(即老年人)的神经精神影响，以及这一群体中甲状腺激素治疗的影响，尽管甲状腺功能障碍与情绪和认知障碍之间的联系得到了很好的证明。这项建议的目的是评估非痴呆老年SCH患者的抑郁和神经心理功能，以及T4治疗在改善这些受试者情绪和认知方面的效果。这项拟议的研究分为两个阶段。在第一阶段，我们将采用横断面设计来评估老年、非痴呆的SCH参与者与正常甲状腺对照组的情绪、认知和身体症状的具体性质、严重程度和模式。在第二阶段，我们将开展一项为期16周的双盲、安慰剂对照研究，研究T4在改善SCH受试者这些措施方面的效果。将测量情绪、认知、生活质量、甲状腺功能减退的身体症状和甲状腺状况(T4、T3、TSH和抗TPO抗体)。这项研究将提供关于SCH对脆弱人群的神经精神影响以及甲状腺激素治疗在减轻症状和改善整体功能方面的效果的重要信息。公共卫生相关性：该项目旨在确定轻度甲状腺功能衰竭(也称为亚临床甲状腺功能减退症)是否存在特定的情绪和认知变化。此外，这项研究还将探讨与亚临床甲状腺功能减退症相关的情绪和认知变化是否会通过甲状腺激素治疗而得到改善。

DESCRIPTION (provided by applicant): Subclinical hypothyroidism is a biochemical diagnosis characterized by elevated thyrotropin (TSH) levels with normal circulating thyroxine (T4) and triiodothyronine (T3) levels. Although SCH does not present with symptoms of clinical hypothyroidism it may be associated with mood, cognitive, and physical symptoms, and increased risk for hyperlipidemia and ischemic heart disease. SCH may also increase vulnerability to depression, cognitive impairment, and dementia. SCH is relatively common and occurs in approximately five to ten percent of the population, with higher prevalence (up to 20%) in women over age 60. To date, there have been no well designed, controlled studies that have evaluated the neuropsychiatric effects of SCH on the most vulnerable population (i.e., elderly individuals), and the impact of thyroid hormone treatment in this group, despite the well documented association between thyroid dysfunction and mood and cognitive disturbance. The purpose of this proposal is to evaluate depression and neuropsychological function in non-demented, elderly individuals with SCH and the efficacy of T4 treatment in improving mood and cognition in these subjects. There are two phases to the proposed study. In phase I, we will employ a cross- sectional design to evaluate the specific nature, severity and pattern of mood, cognitive, and physical symptoms in elderly, non-demented participants with SCH compared with euthyroid controls. In the second phase, we will carry out a double-blind, placebo- controlled, sixteen week study of the effect of T4 in improving these measures in the SCH subjects. Mood, cognition, quality of life, physical symptoms of hypothyroidism and thyroid status (T4, T3, TSH and antithyroperoxidase (anti-TPO) antibodies) will be measured. This study will yield important information about the neuropsychiatric effects of SCH on a vulnerable population and the effect of thyroid hormone treatment in reducing symptoms and improving overall functioning. Public Health Relevance: This project aims to determine whether there are specific alterations of mood and cognition with mild thyroid failure, also known as subclinical hypothyroidism. Furthermore, this research will also address whether alterations of mood and cognition associated with subclinical hypothyroidism are improved with thyroid hormone treatment.