Subclinical thyroid dysfunction in the elderly

描述（由申请人提供）：亚临床甲状腺功能障碍，定义为甲状腺刺激激素水平异常，游离甲状腺素水平正常，常见于老年人。由于甲状腺激素受体在全身的位置以及甲状腺激素在代谢中的重要作用，甲状腺激素状态的紊乱可能引起各种各样的全身效应。亚临床甲状腺功能障碍的适当临床管理是有争议的，这在很大程度上是由于已发表的观察性研究的主要局限性和缺乏大型随机临床试验的数据。我们的中心假设是，患有持续性亚临床甲状腺功能亢进的老年人在特定不良心血管、肌肉骨骼和神经认知预后方面的风险增加，而患有持续性亚临床甲状腺功能减退的老年人则没有这种风险。我们建议在心血管健康研究中使用储存的血液和19年随访期的现有结果数据进行分析，心血管健康研究是一项由美国国立卫生研究院赞助的针对65岁及以上社区居住男性和女性的纵向研究。在我们的第一个目标，我们将检查在这一人群甲状腺功能测试的自然史。在我们的第二个目标中，我们将研究持续性亚临床甲状腺功能亢进与房颤、髋部骨折和痴呆之间的关系。在我们的第三个目标中，我们将研究持续性亚临床甲状腺功能减退与冠心病、充血性心力衰竭和痴呆之间的关系。甲状腺激素是美国第七大常用处方药，但经常没有得到适当的监测。在我们的第四个目标中，我们将定义老年人甲状腺激素治疗过度替代的频率和不良后果。我们将检查与目的2相同的结果，以确定内源性和外源性亚临床甲状腺功能亢进的影响是否相似。在研究期结束时，我们将收集足够的数据来指导内源性和外源性亚临床甲状腺功能障碍的临床管理，并完善亚临床甲状腺功能障碍治疗的随机对照临床试验的目标人群和总体设计。这项研究将解决该领域几个激烈争议的领域，并为亚临床甲状腺功能障碍管理的明确指南奠定基础。公共卫生相关性：亚临床甲状腺功能障碍，定义为高或低促甲状腺激素水平，正常游离甲状腺激素水平，在老年人中很常见。然而，一旦发现这些检测异常，关于适当的管理就存在争议。我们的研究结果将利用现有数据评估治疗的预期风险和益处，以细化临床试验的目标人群。

DESCRIPTION (provided by applicant): Subclinical thyroid dysfunction, defined as an abnormal thyroid stimulating hormone level with a normal free thyroxine level, is common in older individuals. A wide variety of systemic effects are possible from disturbances in thyroid hormone status, due to the location of thyroid hormone receptors throughout the body and the important role that thyroid hormone plays in metabolism. The appropriate clinical management of subclinical thyroid dysfunction is controversial, in large part due to major limitations in the published observational studies and a lack of data from large randomized clinical trials. Our central hypothesis is that older individuals with persistent subclinical hyperthyroidism are at increased risk for specific adverse cardiovascular, musculoskeletal, and neurocognitive outcomes, whereas those with persistent subclinical hypothyroidism are not. We propose to conduct analyses using banked blood and existing outcome data over a 19-year follow-up period in the Cardiovascular Health Study, an established, NIH-sponsored longitudinal study of community-dwelling men and women aged 65 and over. In our first aim, we will examine natural history of thyroid function testing in this population. In our second aim, we will examine the relationship between persistent subclinical hyperthyroidism and incident atrial fibrillation, hip fracture, and dementia, and in our third aim, we will examine the relationship between persistent subclinical hypothyroidism and incident coronary heart disease, congestive heart failure, and dementia. Thyroid hormones are the seventh most commonly prescribed drugs in the US, and frequently are not appropriately monitored. In our fourth aim, we will define the frequency and adverse consequences of overreplacement with thyroid hormone therapy in an older population. We will examine the same outcomes as in aim 2, to ascertain whether the effects of endogenous and exogenous subclinical hyperthyroidism are similar. By the end of the proposed study period, we will have assembled sufficient data to guide clinical management of both endogenous and exogenous subclinical thyroid dysfunction and to refine the target population and overall design of randomized, controlled clinical trials of therapy for subclinical thyroid dysfunction. This research will resolve several areas of intense controversy in the field and set the stage for definitive guidelines for management of subclinical thyroid dysfunction. PUBLIC HEALTH RELEVANCE: Subclinical thyroid dysfunction, defined as high or low thyroid stimulating hormone levels with normal free thyroid hormone levels, is common in older people. However, once these testing abnormalities are discovered, there is controversy regarding appropriate management. Our findings will assess the anticipated risks and benefits of treatment using existing data, to refine the target population for a clinical trial.