SIMPLIFIED POPULATION SCREENING FOR ADULT HYPOTHYROIDISM

甲状腺功能减退症是某些人群中的一种常见疾病，由于微妙的、非特异性的症状和体征，通常不能及早诊断。使用滤纸干血斑(DBS)筛查新生儿的方法非常经济高效且准确，可应用于儿科和成人人群，在残疾和严重症状出现之前检测疾病，并在治疗期间监测患者，提供比传统方法更高的成本效益、相当的准确性和更好的患者依从性。我们建立和验证了敏感和准确的方法来检测DBS标本中的促甲状腺激素(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)。具体目标：我们将从以下三个易患自身免疫性甲状腺炎和甲状腺功能减退症的高危人群中收集DBS样本：(A)每年将对目前居住在护养院和个人护理院的老年人口进行筛查，为期两年。(B)母亲在被诊断为怀孕时、例行六周探视和产后一年探视时将接受筛查，因为她们在产后第一年患甲状腺机能减退症的风险增加，而且如果母亲在怀孕早期患有甲状腺机能减退症，可能会对未出生的婴儿产生有害影响。(三)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%。我们正在检测DBS样本中的甲状腺抗体，每年采集血液进行常规筛查甲状腺功能减退或其他检查，作为其常规医疗保健的一部分，以确定甲状腺抗体的存在是否可以预先选择那些需要进行年度TSH筛查的患者。将开发DBS样本收集试剂盒，以便向患者或医疗保健专业人员提供DBS样本，以便收集DBS样本并将其邮寄到人口筛查实验室，以测定TSH和甲状腺抗体。可以确定人口的材料、样本收集、运输和测试的成本，并将其与收集、运输和测试血清样本以测量这些相同测试的成本进行比较。有了这些信息和三个被研究人群中甲状腺功能减退和甲状腺炎患病率的数据，我们可以确定使用一种非常低成本、准确方法测量的容易收集的样本来筛查甲状腺功能减退风险增加的成年人的成本效益。这项研究的结果将决定这种筛查方法是否适用于高危人群。拟议的商业应用：类似于目前规定的、非常经济高效的新生儿遗传和代谢性疾病人群筛查，区域商业实验室可以开发和实施对大量成年人的筛查。由于患者、亲属、朋友或健康护理专业人员(包括医生办公室)可以很容易地收集四到八滴血液并将样本邮寄到实验室，因此使用干血斑滤纸样本可以提高商业应用的成本节约，成本比收集和运输血清样本低得多。对大量人群进行筛查，并使用非常便宜的标本，大大提高了检测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.