COMPARISON OF THYROID HORMONE LEVELS FOUND WITH NORMAL THYROID FUNCTIONING, C

甲状腺激素水平与正常甲状腺功能的比较，C

• 批准号: 7719028
• 负责人: JACQUELINE JONKLAAS
• 金额: $ 1.58万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719028
• 关键词: Benign; Biochemical; Biochemical Markers; Blood Circulation; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; DNA Microarray Chip; DNA Microarray format; Disease; Funding; Genes; Gland; Grant; Half-Life; Hypothyroidism; Individual; Institution; Malignant neoplasm of thyroid; Microarray Analysis; Moods; Neuropsychology; Operative Surgical Procedures; Participant; Patient Preferences; Patients; Physiological; Replacement Therapy; Research; Research Personnel; Resources; Schedule; Serum; Signs and Symptoms; Source; Standards of Weights and Measures; Testing; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroid carcinoma; Thyroidectomy; Thyrotropin; Thyroxine; Time; Treatment Protocols; Triiodothyronine; United States National Institutes of Health; indexing; psychologic; satisfaction

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this project is to determine what combination of thyroid hormones provides optimum replacement therapy for hypothyroidism. In an individual with a functioning thyroid gland there are two circulating thyroid hormones, thyroxine and triiodothyronine. Although some triiodothyronine is produced within the thytoid gland itself, the majority is produced in the periphery from thyroxine. Triiodothyronine also has a much shorter half-life than thyroxine. At the present time, standard thyroid hormone replacement consists of synthetic thyroxine (levothyroxine) alone. Although levothyroxine is converted into triiodothyronine in the circulation, it is not clear that the triiodothyronine levels with replacement therapy are equal to those seen with intact thyroid function. A recent study using a combination of levothyroxine and triiodothyronine indicated a patient preference for the combination therapy. Therefore, the overall hypothesis of this project is that levothyroxine replacement results in a subtle deficiency of triiodothyronine, and that levothyroxine thus provides incomplete treatment for hypothyroidism. Specific Aim 1: To compare circulating thyroxine and triiodothyronine concentrations in individuals with normal thyroid function, prior to thyroidectomy, with concentrations achieved form thyroid hormone replacement with levothyroxine, after thyroidectomy. The initial hypothesis to be tested in this project is whether, within individual patients, standard replacement with levothyroxine alone results in lower serum levels of triiodothyronine than those seen while the thyroid gland is functioning. Participants will be euthyroid individuals who are scheduled for thyroidectomy for benign nodular disease or thyroid cancer. Serum triiodothyronine levels prior to thyroid surgery will be compared with those after thyroidectomy when participants have been stabilized on levothyroxine therapy, in order to determine if levothyroxine replacement results in lower, sub-physiologic triiodothyronine levels. Specific Aim 2: To identify a panel of genes whose level of expression is altered by thyroid hormone. Adequate treatment of hypothyroidism is judged by many parameters. These include thyroid hormone and thyroid stimulating hormone levels: signs, symptoms, and biochemical indices of thyroid status; and patient mood, neuropsychologic functioning, and satisfaction. Another hypothesis of this project is that a panel of genes can be identified whose expression level is reflective of thyroid status. Complimentary DNA microarray technology will be used to develop a gene panel whose expression is regulated by thyroid hormone. Such an index of thyroid status should be particularly sensitive to changes in thyroid hormone levels, and to addition of triiodothyronine to a treatment regimen. This gene panel will be included in the biochemical markers used to assess thyroid status in specific aims three and four. Specific Aim 3: To compare several replacement regimens using different ratios of levothyroxine and triiodothyronine, to determine which has the most favorable impact on indices of thyroid status. In addition, the triiodothyronine level achieved by the regimen that best reverses the indices of hypothyroidism will be compared with the levels of triiodothyronine seen with intact thyroid function. The third hypothesis is that levothyroxine/triiodothyronine combination will provide superior treatment of hypothyroidism. Biochemical, physiologic and psychologic indices of thyroid status will be compared during combination therapy with several ratios of levothyroxine and triiodothyronine to indices during treatment with levothyroxine alone. Serum triiodothyronine levels will also be correlated with thyroid status to determine if the regimen that most closely reproduces the triiodothyronine levels seen with intact thyroid function also has the most favorable impact on the physiologic, biochemical, and psychologic indices of thyroid status. Specific Aim 4: To compare indices of thyroid hormone status during replacement with a levothyroxine/sustained release triiodothyronine combination to indices achieved with an optimal levothyroxine/triiodothyronine regimen. The final hypothesis of this project is that sustained release triiodothyronine will be superior to commercially available triiodothyronine. Because of its short half-life, replacement with triiodothyronine leads to considerable fluctuations in its circulating levels. Use of a new sustained release product, which results in steady triiodothyronine levels, will furnish more physiologic replacement. This will be tested against treatment with levothyroxine, and levothyroxine and triiodothyronine.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的目的是确定甲状腺激素的哪种组合为甲状腺功能减退症提供了最佳的替代疗法。在具有正常甲状腺功能的个体中，有两种循环的甲状腺激素，甲状腺素和三碘甲醇。尽管某些三碘甲状腺素是在甲状腺本身内产生的，但大多数是在甲状腺素的外围产生的。三碘甲状腺素的半衰期也比甲状腺素短得多。目前，标准的甲状腺激素替代物仅由合成甲状腺素（左甲状腺素）组成。尽管左甲状腺素在循环中被转化为三碘甲状腺素，但尚不清楚带有替代疗法的三碘甲状腺素水平等于具有完整的甲状腺功能的甲状腺素。最新的研究结合了左甲状腺素和三碘甲状腺素，表明患者对联合疗法的偏爱。因此，该项目的总体假设是左甲状腺素替代导致三一个甲基氨酸的细微缺乏，因此左甲状腺素因此为甲状腺功能减退提供了不完整的治疗方法。 具体目的1：比较甲状腺切除术之前正常甲状腺功能的个体中甲状腺素和三碘甲状腺素浓度的比较，在甲状腺切除术后，甲状腺激素的浓度与甲状腺素替代形成甲状腺激素替代。 在该项目中要检验的最初假设是，在个别患者中，单独用左甲状腺素的标准替代方法是否会导致三碘甲状腺素的血清水平较低，而甲状腺腺体发挥作用时所见。参与者将是原定于甲状腺切除术的甲状腺功能低下的个体。甲状腺手术前的血清三一个甲状腺素水平将与甲状腺切除术后的甲状腺切除术后的甲状腺素疗法稳定时，以确定左甲状腺素替代的替代是否会导致左丝甲状腺素的替代是否会导致较低的下型三碘二硫代肌氨酸水平。 特定目的2：确定一组基因，其表达水平被甲状腺激素改变。甲状腺功能减退症的适当治疗受许多参数判断。其中包括甲状腺激素和甲状腺刺激激素水平：甲状腺状态的体征，症状和生化指标；和患者的情绪，神经心理功能和满意度。该项目的另一个假设是，可以鉴定出一组基因的表达水平反映甲状腺状态。免费DNA微阵列技术将用于开发一个基因面板，其表达受甲状腺激素调节。这种甲状腺状态的指数应特别敏感甲状腺激素水平的变化，并将三碘甲氨酸添加到治疗方案中。该基因面板将包括在用于评估甲状腺状态的生化标记中，以三个和四个目的。 特定目的3：使用不同比率的左甲状腺素和三碘甲基氨酸比较几种替代方案，以确定哪些对甲状腺状态指数的影响最大。此外，将最能逆转甲状腺功能减退症指数的治疗方案所达到的三碘甲状腺素水平将与具有完整的甲状腺功能的三碘甲醇水平进行比较。 第三个假设是左甲状腺素/三碘甲状腺素组合将提供甲状腺功能减退症的卓越治疗。在联合疗法期间，将比较甲状腺状态的生化，生理和心理指标，单独使用左甲状腺素治疗期间，左甲状腺素和三碘甲状腺素与指数的多种比例将进行比较。血清三一个甲状腺素水平也将与甲状腺状态相关，以确定最紧密地再现具有完整甲状腺功能的三碘甲状腺素水平的方案是否对甲状腺状态的生理，生物化学和心理学索引。 特定目的4：将替代过程中甲状腺激素状态的指标与左甲状腺素/持续释放的三碘甲氨酸组合与使用最佳左丝甲甲状腺素/三碘甲状腺素方案获得的指数进行比较。 该项目的最终假设是，持续释放的三碘甲糖胺将优于市售的三碘甲醇。由于其半衰期较短，因此替代了三碘甲状腺素，导致其循环水平发生了相当大的波动。使用新的持续释放产品，从而导致稳定的三碘甲醇水平，将提供更多的生理替代品。这将在用左甲状腺素，左甲状腺素和三碘甲状腺素治疗的治疗中进行测试。