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

描述（由申请人提供）：亚临床甲状腺功能减退症是一种生化诊断，其特征是促甲状腺素（TSH）水平升高，循环甲状腺素（T4）和三碘甲状腺原氨酸（T3）水平正常。虽然SCH不表现为临床甲状腺功能减退的症状，但它可能与情绪、认知和身体症状以及高脂血症和缺血性心脏病的风险增加有关。SCH还可能增加抑郁、认知障碍和痴呆的易感性。SCH相对常见，约占人口的5%至10%，60岁以上妇女的患病率更高（高达20%）。迄今为止，尽管甲状腺功能障碍与情绪和认知障碍之间有充分的文献记录，但还没有设计良好的对照研究来评估SCH对最脆弱人群（即老年人）的神经精神影响，以及甲状腺激素治疗对这一群体的影响。本研究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治疗对这些患者情绪和认知的改善效果。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SCH患者与正常甲状腺对照者的情绪、认知和身体症状的具体性质、严重程度和模式。在第二阶段，我们将开展一项双盲、安慰剂对照、为期16周的研究，研究T4在改善SCH受试者这些指标方面的效果。测量患者的情绪、认知、生活质量、甲状腺功能减退的身体症状和甲状腺状态（T4、T3、TSH和抗甲状腺过氧化物酶（anti-TPO）抗体）。本研究将提供关于SCH对易感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作用的重要信息。公共卫生相关性：本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）患者是否存在特定的情绪和认知改变。此外，本研究还将探讨与亚临床甲状腺功能减退相关的情绪和认知改变是否可以通过甲状腺激素治疗得到改善。

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.