LEVOTHYROXINE: TRIIODOTHYRONINE COMBINATION THERAPY

左旋甲状腺素：三碘甲状腺原氨酸联合疗法

• 批准号: 6721117
• 负责人: JACQUELINE JONKLAAS
• 金额: $ 14.15万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6721117
• 关键词: biochemistry; blood chemistry; clinical research; clinical trials; combination chemotherapy; endocrine disorder chemotherapy; gene expression; hormone therapy; human subject; human therapy evaluation; hypothyroidism; microarray technology; neuropsychology; patient oriented research; psychophysiology; thyroid function; thyroidectomy; thyroxine analog; triiodothyronine

DESCRIPTION (provided by applicant): The objective of this project is to determine what combination of thyroid hormones provides optimum replacement therapy for hypothyroidism. There are two circulating thyroid hormones, thyroxine and triiodothyronine, and standard thyroid hormone replacement consists of synthetic thyroxine (levothyroxine) alone. Although levothyroxine is converted into triiodothyronine in the circulation, triiodothyronine levels achieved may not be equal to those seen with intact thyroid function. Therefore, the overall hypothesis of this project is that levothyroxine replacement results in a subtle deficiency of triiodothyronine and provides incomplete treatment for hypothyroidism. The initial hypothesis to be tested in this project is whether, within individual patients, standard replacement with levothyroxine results in lower serum levels of triiodothyronine than those seen while the thyroid gland is functioning. Participants will be euthyroid individuals scheduled for thyroidectomy for benign nodular disease or thyroid cancer. Serum triiodothyronine levels prior to thyroid surgery will be compared with those after thyroidectomy, to determine if levothyroxine replacement results in lower, sub-physiologic triiodothyronine levels. Another hypothesis of this project is that a panel of genes can be identified whose expression level is reflective of thyroid status. Complimentary (c) DNA array technology will be used to develop a gene panel whose expression is regulated by thyroid hormone. This gene panel will be included in the biochemical markers used to assess thyroid status. The third hypothesis is that levothyroxinetriiodothyronine 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. The regimens will be compared to determine if the one that most closely reproduces the triiodothyronine levels seen with intact thyroid function, also has the most favorable impact on thyroid status. The final hypothesis of this project is that sustained release triiodothyronine is superior to commercially available triiodothyronine. Because of its short half-life, replacement with triiodothyronine leads to fluctuating serum levels. 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.

描述（由申请人提供）：本项目的目标是 确定哪种甲状腺激素组合提供最佳替代 治疗甲状腺功能减退症 有两种甲状腺激素循环， 甲状腺素和三碘甲状腺原氨酸，以及标准甲状腺激素替代 由单独的合成甲状腺素（左旋甲状腺素）组成。 虽然左旋甲状腺素 在循环中转化为三碘甲状腺原氨酸， 实现的甲状腺功能可能不等于甲状腺功能完好时所见的。 因此，本项目的总体假设是， 替代导致三碘甲状腺原氨酸的微妙缺乏， 甲状腺功能减退症治疗不彻底。 待检验的初始假设 在这个项目中，是否在个别患者中， 与左旋甲状腺素相比， 甲状腺功能正常时所见。 参与者将被 甲状腺功能正常者因良性结节性疾病拟行甲状腺切除术 或甲状腺癌。 甲状腺手术前血清三碘甲腺原氨酸水平 将与甲状腺切除术后的患者进行比较，以确定左旋甲状腺素是否 替代导致较低的亚生理三碘甲状腺原氨酸水平。 该项目的另一个假设是，可以识别一组基因， 其表达水平反映了甲状腺状态。 DNA（C）DNA 阵列技术将用于开发一个基因面板，其表达是 由甲状腺激素调节。 该基因组将被纳入 用于评估甲状腺状态的生化标志物。 第三个假设是 左旋甲状腺素三碘甲状腺原氨酸组合将提供上级治疗 甲状腺功能减退症 生化、生理和心理指标 在联合治疗期间，将使用几个比率比较甲状腺状态 治疗期间的指标 单独使用左旋甲状腺素。 将对这些方案进行比较，以确定 最接近地再现了完整的 甲状腺功能，也对甲状腺状态有最有利的影响。 的 本项目的最终假设是缓释三碘甲腺原氨酸是 其上级于市售的三碘甲状腺原氨酸。 由于其短 半衰期，用三碘甲状腺原氨酸替代导致血清 程度. 一种新的缓释产品， 三碘甲腺原氨酸水平，将提供更多的生理替代。 这将 对左旋甲状腺素治疗进行测试，左旋甲状腺素和 三碘甲腺原氨酸