MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD

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可提供最佳替代方案 甲状腺功能减退症的治疗。有两种循环中的甲状腺激素， 甲状腺激素和三碘甲腺原氨酸与标准甲状腺激素替代 由合成的甲状腺激素(左旋甲状腺素)单独组成。虽然左旋甲状腺素 在循环中转化为三碘甲状腺原氨酸，三碘甲状腺原氨酸水平 取得的效果可能不等同于甲状腺功能完整的患者。 因此，该项目的总体假设是左旋甲状腺素 替代会导致三碘甲腺原氨酸的轻微缺陷，并提供 对甲状腺功能减退症的不完全治疗。要检验的初始假设 在这个项目中，是否在个别患者中进行标准的替代 左旋甲状腺素导致血清三碘甲腺原氨酸水平低于 这些是在甲状腺功能正常时看到的。参与者将是 甲状腺功能正常的患者因良性结节疾病行甲状腺切除术 或者是甲状腺癌。甲状腺手术前血清三碘甲状腺原氨酸水平 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 替代会导致较低的亚生理性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 其表达水平能反映甲状腺状况。免费赠送(C)DNA 将利用阵列技术开发一种表达为 受甲状腺激素的调节。这个基因小组将被包括在 用于评估甲状腺状况的生化标记物。第三个假设是 左旋甲状腺素联合三碘甲腺原氨酸将提供更好的治疗 甲状腺功能减退症。生化、生理和心理指标 甲状腺状况将在几种比例的联合治疗中进行比较 左旋甲状腺素和三碘甲腺原氨酸对甲状旁腺素治疗期间指标的影响 单独使用左旋甲状腺素。将对这些方案进行比较，以确定是否 最接近地再现了三碘甲腺原氨酸的水平 甲状腺功能，对甲状腺状况也有最有利的影响。这个 该项目的最终假设是缓释三碘甲腺原氨酸是 优于市售的三碘甲腺原氨酸。因为它很短 半衰期，用三碘甲腺原氨酸替代会导致血清波动 级别。一种新的缓释产品，导致稳定的 三碘甲腺原氨酸水平，将提供更多的生理替代。这将是 与左旋甲状腺素和左旋甲状腺素进行对比试验 三碘甲腺原氨酸。

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.