THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS

甲状腺激素(TH)的抑制疗法已用于 良性甲状腺疾病90多年的治疗。行政管理 外源性TH超过正常分泌的甲状腺引导物 由于血清促甲状腺激素(TSH)水平的降低，脑下垂体 刺激甲状腺生长的激素。抑制TSH应 导致良性结节缩小(或进一步生长减少) 或者是甲状腺肿。最近的几项研究表明，这可能是 在缩小结核大小或防止结核生长方面效果不佳 甲状腺肿大。TH疗法也可能对骨骼产生不利影响；几个 研究表明，长期使用抑制性或甚至 生理剂量的TH会导致骨骼中钙的显著损失 并且会使这些患者面临更高的骨折风险 脊椎、臀部和手腕。这些问题对 女性患甲状腺疾病的几率是男性的7-10倍 结节或甲状腺肿，并有更大的风险发展为 骨质疏松症和骨折。这项拟议研究的目标是 前瞻性地评估其有效性和不利影响 TH抑制疗法对骨骼和良性甲状腺疾病的影响。这个 这项建议的具体目的是：1)评估 抑制性TH治疗良性结节和甲状腺肿 2)评估TH疗法是否产生显著的骨丢失 肿块3)以确定良性甲状腺组织的萎缩或过度 骨丢失取决于TSH抑制的程度和4) 评估TH治疗对患者生活质量的影响。这 需要信息来确定目前接受的治疗方法是否 要么不合适，要么需要以特定的方式进行管理 既有效又安全。这项研究的这些结果也将具有 对850万接受TH治疗的患者(主要是女性)的影响 原发性甲状腺功能减退症或甲状腺癌的治疗。具体的 AIMS将以前瞻性、双盲、安慰剂对照的方式进行评估 抑制性甲状腺激素(T4)治疗女性良性结节的研究 或者是甲状腺肿。在接受活性T4的患者中，剂量将通过以下方式调整 一种高灵敏度的TSH测定，并将TSH值维持在两个值中的一个 降低了级别。患者将接受为期两年的治疗 尿骨和血清骨标志物的基线和系列测定 再吸收和形成，生活质量的评估，测定 使用双光子x射线骨密度仪(一种高度的 灵敏和精确的技术)和客观的甲状腺测量 使用高分辨率实时超声测量腺体和结节的大小。

Suppressive therapy with thyroid hormone (TH) has been used in the management of benign thyroid disorders for over 90 years. Administration of exogenous TH in excess of normal production by the thyroid gland leads to a reduction in the serum level of thyrotropin (TSH), the pituitary hormone which stimulates thyroid gland growth. TSH suppression should lead to shrinkage (or a reduction in further growth) of benign nodules or goiter. Several recent studies have suggested that TH may be ineffective in reducing the size of nodules or preventing the growth of goiters. TH therapy may also have adverse effects on bone; several studies have suggested that prolonged treatment with suppressive or even physiologic doses of TH leads to a significant loss of calcium from bone and would pre.dispose these patients to an increased risk for fractures of the spine, hip and wrist. These issues are especially important to women since they are 7 - 10 times as likely as men to have thyroid nodules or goiters and are at greater risk for the development of osteoporosis and fracture. The goal of this proposed study is to prospectively evaluate both the effectiveness and the detrimental effects of TH suppressive therapy on bone and benign thyroid diseases. The specific aims of this proposal are 1) to evaluate the effectiveness of suppressive TH therapy in the management of benign nodules and goiter, 2) to evaluate whether TH therapy produces a significant loss of bone mass 3) to establish whether shrinkage of benign thyroid tissue or excess bone loss is dependent upon the extent of TSH suppression and 4) to evaluate the effect of TH therapy on the patient's quality of life. This information is needed to determine whether a currently accepted therapy is either inappropriate or needs to be administered in a specific way to be both effective and safe. These results of this study will also have implications for the 8.5 million patients (mostly women) receiving TH for the treatment of primary hypothyroidism or thyroid cancer. The specific aims will be evaluated in a prospective, double-blind, placebo controlled study of suppressive thyroxine (T4) therapy in women with benign nodules or goiters. In patients receiving active T4, doses will be adjusted using a highly sensitive TSH assay and maintaining TSH values at one of two reduced levels. Patients will be followed for 2 years on therapy with baseline and serial measurements of urine and serum markers for bone resorption and formation, evaluations of quality of life, determination of bone mineral density using dual-photon x-ray absorptiometry (a highly sensitive and precise technique) and objective measurements of thyroid gland and nodule size using high resolution, real time ultrasound.