THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS

甲状腺激素对骨骼和甲状腺疾病的影响

• 批准号: 2377795
• 负责人: DAVID H SARNE
• 金额: $ 23.39万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2377795
• 关键词: biomarker; blood chemistry; bone density; bone metabolism; clinical trials; drug adverse effect; endocrine disorder chemotherapy; endocrine pharmacology; female; goiter; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; longitudinal human study; photon absorptiometry; physiologic bone resorption; pituitary thyroid axis; quality of life; thyroid disorder; thyroid function; thyrotropin; thyroxine; ultrasonography; urinalysis

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.

用甲状腺激素（Th）抑制疗法已在 良性甲状腺疾病的管理已有90多年的历史。行政 甲状腺导线超过正常产生的外源性TH 降低甲状腺蛋白（TSH）的血清水平，垂体 刺激甲状腺生长的激素。 TSH抑制作用应该 导致良性结节的收缩（或进一步生长的减少） 或Goiter。 最近的一些研究表明，可能是 无效减少结节的大小或防止生长 山雀。治疗也可能对骨骼产生不利影响。一些 研究表明，抑制性甚至什至 TH的生理剂量导致骨骼严重损失 并将这些患者预见到骨折的风险增加 脊柱，臀部和腕部。这些问题对于 女性由于男性的7-10倍，甲状腺的可能性是男性的7-10倍 结节或山雀，并且有更大的风险 骨质疏松和骨折。这项拟议的研究的目的是 前瞻性评估有效性和有害影响 TH抑制骨骼和良性甲状腺疾病的抑制疗法。这 该提案的具体目的是1）评估的有效性 抑制良性结节和甲状腺肿的管理疗法， 2）评估该治疗是否会产生骨骼的重大损失 质量3）确定良性甲状腺组织的收缩还是多余 骨质流失取决于TSH抑制程度，4） 评估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 是不合适的，要么需要以特定方式管理 既有效又安全。这项研究的这些结果也将有 对850万患者（主要是妇女）的影响 原发性甲状腺功能减退症或甲状腺癌的治疗。具体 目标将在预期的双盲，安慰剂控制中评估 良性结节女性抑制性甲状腺素（T4）疗法的研究 或山雀。在接受活动T4的患者中，将使用 高度敏感的TSH分析并保持在两个之一的TSH值 降低水平。患者将接受2年的治疗 骨骼的尿液和血清标记的基线和系列测量 吸收和形成，评估生活质量，决心 使用双光子X射线吸收法（高度高度）的骨矿物质密度 敏感且精确的技术）和甲状腺的客观测量 腺体和结节尺寸使用高分辨率，实时超声。