SIMPLIFIED POPULATION SCREENING FOR ADULT HYPOTHYROIDISM

胸腺功能减退症是一种常见病，在某些人群中，往往不能早期诊断，因为微妙的，非特异性的症状和体征。采用滤纸干血点（DBS）筛查新生儿的非常具有成本效益和准确性的方法，可应用于儿科和成人人群，以便在残疾和出现严重症状之前发现疾病，并在治疗期间监测患者，与传统方法相比，具有更高的成本效益、相当的准确性和更高的患者依从性。我们建立并验证了一种灵敏、精确的方法来测量DBS标本中促甲状腺激素（TSH）和甲状腺抗体、甲状腺过氧化物酶抗体（TPOAb）和甲状腺球蛋白抗体（TGAb）。具体目的：我们将从以下三种自身免疫性甲状腺炎和甲状腺功能减退的高危人群中收集DBS标本：(a)目前居住在护理和个人护养院的老年人每年进行筛查，为期两年。(b)母亲在怀孕诊断、六周例行检查和产后一年例行检查时将接受检查，因为她们在产后第一年患甲状腺功能减退的风险增加，而且如果母亲在怀孕早期出现甲状腺功能减退，可能对未出生的婴儿产生有害影响。(c)胰岛素依赖型糖尿病（IDDM）患者患自身免疫性甲状腺疾病的风险为30%至40%。当每年采集血液常规筛查甲状腺功能减退或作为常规医疗保健的一部分进行其他检查时，我们测量DBS标本中的甲状腺抗体，以确定甲状腺抗体的存在是否可以预先选择需要每年进行TSH筛查的患者。我们将开发脑起搏器样本收集包，以便提供给病人或医护人员，方便收集和邮寄脑起搏器样本到人口筛查实验室，以测量TSH和甲状腺抗体。可以确定人群的材料、标本收集、运输和检测的成本，并将其与收集、运输和检测血清标本以进行这些相同检测的成本进行比较。有了这些信息和三个研究人群中甲状腺功能减退和甲状腺炎患病率的数据，我们可以确定筛查甲状腺功能减退风险增加的成年人的成本效益，使用一种非常低成本，准确的方法，使用易于收集的标本进行测量。这项研究的结果将决定这种筛查方法对高危人群的适宜性。拟议的商业应用：类似于目前强制性的、非常具有成本效益的新生儿遗传和代谢疾病人群筛查，筛查大量成年人可以由区域商业实验室开发和实施。由于患者、亲属、朋友或包括医生办公室在内的卫生保健专业人员可以轻松地收集4至8滴血液并将标本邮寄到化验室，比收集和运输血清标本的成本低得多，因此使用干血斑点滤纸标本可以提高商业应用的成本节约。筛选大量人群和使用非常便宜的标本大大提高了测试的成本效益和这项技术的商业应用。

Hypothymidism is a common disease in certain populations, and often is not diagnosed early because of subtle, non-specific symptoms and signs. The adaptation of the very cost effective and accurate method for screening newborn infants using filter paper dried blood spots (DBS) can be applied to pediatric and adult populations to detect diseases before disability and severe symptoms develop, and to monitor patients during therapy, providing greater cost effectiveness, comparable accuracy and greater patient compliance than found with traditional methods. We developed and validated sensitive and precise methods to measure thyroid stimulating hormone (TSH)and the thyroid antibodies, thyroperoxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb)in DBS specimens. Specific Aims: We shall collect DBS specimens from the following three populations who are at high risk for the development of autoimmune thyroiditis and hypothyroidism: (a) An elderly population currently Living in Nursing and Personal Care Homes will be screened annually for two years. (b) Mothers at diagnosis of pregnancy, at their routine six week visit and at their one year postpartum visit will be screened because they are at increased risk for hypothyroidism during the first postpartum year, and because there may be a deleterious effect on the unborn child if the mother is hypothyroid during early pregnancy. (c) Patients with insulin dependent diabetes mellitus (IDDM) have a 30 to 40% risk of autoimmune thyroid diseases. We are measuring thyroid antibodies in DBS specimens when blood is collected annually to routinely screen for hypothyroidism or for other tests as part of their routine medical care to determine if the presence of thyroid antibodies can preselect those patients who need annual TSH screening. DBS specimen collection kits will be developed so they can be provided to patients or health care professionals to facilitate the collection and mailing of DBS specimens to a population screening Laboratory for the measurement of TSH and thyroid antibodies. The cost for materials, specimen collection, transportation and testing of the populations can be established and compared to the cost to collect, transport and test serum specimens to measure these same tests. With this information and the data on the prevalence of hypothyroidism and thyroiditis in the three populations studied, we can determine the cost effectiveness of screening adults who are at increased risk for hypothyroidism using an easily collected specimen measured by a very Low cost, accurate method. The results of this study will determine the appropriateness of this screening methodology for the populations at risk. PROPOSED COMMERCIAL APPLICATION: Analogous to the currently mandated, very cost-effective population screening of newborns for genetic and metabolic diseases, screening Large populations of adults can be developed and implemented by regional commercial Laboratories. The cost savings for commercial applications is enhanced by the use of the dried blood spotted filter paper specimen since the patient, relative, friend or health care professional including the physician's office can easily collect the four to eight drops of blood and mail the specimen to the Laboratory at a much Lower cost than the collection and shipment of serum specimens. Screening Large populations and using very inexpensive specimens greatly enhance the cost- effectiveness of the test and the commercial application of this technology.