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

描述（由申请方提供）：亚临床甲状腺功能减退症是一种生化诊断，特征为促甲状腺激素（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不存在临床甲状腺功能减退症的症状，但它可能与情绪、认知和身体症状相关，并增加高脂血症和缺血性心脏病的风险。SCH还可能增加抑郁症、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岁以上女性的患病率更高（高达20%）。迄今为止，还没有设计良好的对照研究评估SCH对最脆弱人群（即，老年人），以及甲状腺激素治疗在这一群体中的影响，尽管甲状腺功能障碍与情绪和认知障碍之间存在有据可查的关联。本提案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的情绪和认知方面的疗效。拟议的研究分为两个阶段。在第I阶段，我们将采用横断面设计，评价与甲状腺功能正常对照组相比，老年非痴呆SCH受试者的情绪、认知和躯体症状的具体性质、严重程度和模式。在第二阶段，我们将进行一项双盲、安慰剂对照、为期16周的研究，研究T4在改善SCH受试者的这些指标方面的作用。将测量情绪、认知、生活质量、甲状腺功能减退症的身体症状和甲状腺状态（T4、T3、TSH和抗甲状腺过氧化物酶（抗TPO）抗体）。这项研究将产生重要的信息，SCH对脆弱人群的神经精神影响和甲状腺激素治疗在减轻症状和改善整体功能方面的作用。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）是否存在情绪和认知的特定改变。此外，本研究还将探讨甲状腺激素治疗是否能改善亚临床甲状腺功能减退症相关的情绪和认知改变。

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.