THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS

甲状腺激素（TH）抑制疗法已用于 治疗良性甲状腺疾病90多年。管理 外源性TH超过正常生产的甲状腺导致 促甲状腺激素（TSH）的血清水平降低，垂体 刺激甲状腺生长的激素。TSH抑制应该 导致良性结节收缩（或进一步生长减少 或甲状腺肿。 最近的几项研究表明，TH可能是 在减少结核的大小或防止结核的生长方面无效 甲状腺肿TH疗法也可能对骨骼产生不良影响; 研究表明，长时间的抑制性治疗， 生理剂量的TH导致骨中钙的显著损失 并且会使这些患者的骨折风险增加 脊椎，臀部和手腕的肌肉这些问题对于 妇女，因为她们患甲状腺疾病的可能性是男子的7 - 10倍。 结节或甲状腺肿，并在更大的风险，发展 骨质疏松症和骨折。这项研究的目的是 前瞻性地评估有效性和有害影响 TH抑制疗法在骨和良性甲状腺疾病中的应用。的 该提案的具体目标是：（1）评估 在良性结节和甲状腺肿的管理中抑制TH治疗， 2)评估TH治疗是否会导致显著的骨丢失 肿块3）确定是否为良性甲状腺组织萎缩或过度 骨质流失取决于TSH抑制的程度，以及4） 评价TH治疗对患者生活质量的影响。这 需要信息来确定当前接受的治疗是否 要么是不合适的，要么是需要以特定的方式管理， 既有效又安全。这项研究的结果也将有 对850万接受TH治疗的患者（主要是女性）的影响， 治疗原发性甲状腺功能减退症或甲状腺癌。具体 将在前瞻性、双盲、安慰剂对照的 女性良性结节抑制性甲状腺素（T4）治疗研究 或甲状腺肿。在接受活性T4治疗的患者中，将使用 高灵敏度的TSH检测，并将TSH值维持在两个 降低水平。患者将接受2年的随访， 尿和血清骨标志物的基线和系列测量 吸收和形成，生活质量评价，测定 使用双光子X射线骨密度仪（一种高度 灵敏和精确的技术）和客观测量甲状腺 使用高分辨率、真实的时间超声测量腺体和结节大小。

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.