Levothyroxine Dosing in Older Individuals

老年人的左旋甲状腺素剂量

• 批准号: 10638015
• 负责人: ANNE R CAPPOLA
• 金额: $ 59.16万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638015
• 关键词: Adult; Age; Atrial Fibrillation; C-telopeptide; Cardiovascular system; Clinical; Clinical Treatment; Clinical Trials; Cognitive; Confidence Intervals; Data; Diabetes Mellitus; Disease; Dose; Double-Blind Method; Drug Prescriptions; Elderly; Frequencies; Functional disorder; Goals; Guidelines; Health; Health Expenditures; Health Status; Hip Fractures; Hypertension; Hypoglycemia; Hypotension; Hypothyroidism; Individual; LDL Cholesterol Lipoproteins; Laboratories; Left; Lipids; Measures; Medicare; Memory; Monitor; Moods; Musculoskeletal; Observational Study; Outcome; Patient Outcomes Assessments; Patients; Persons; Physiological; Population; Population Distributions; Quality of life; Questionnaires; Randomized; Reference Values; Risk; Risk Reduction; Risk-Benefit Assessment; Sleep; Symptoms; Testing; Therapeutic Index; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Titrations; Weight; aged; blood pressure control; bone turnover; clinical practice; clinically relevant; cognitive function; cognitive testing; cost; evidence base; executive function; flexibility; glycemic control; overtreatment; peer; pharmacologic; primary outcome; randomized placebo-controlled clinical trial; secondary outcome

PROJECT SUMMARY Approximately 10% of US adults aged 65 years or older take levothyroxine to treat hypothyroidism. Guidance for its management has vast and important implications for the health and health care expenditures of millions of older people. Levothyroxine has a narrow therapeutic index that requires monitoring of dosing through thyroid stimulating hormone (TSH) testing. The current TSH reference range is based on the population distribution of younger people, despite evidence for a shift to higher levels with increasing age. Furthermore, observational data do not demonstrate adverse clinical consequences if people with TSH levels just above the reference range are left untreated, and a large clinical trial of people aged 65 years or older showed no benefit to treating this group of patients with levothyroxine. The trial of treatment of subclinical hypothyroidism used low doses of levothyroxine because of underlying endogenous thyroid function. These data may not be generalizable to individuals who have no endogenous thyroid function and rely entirely on exogenous levothyroxine. Small trials in younger people taking levothyroxine suggest that there are no physiologic differences between higher doses of levothyroxine that maintain TSH levels in the lower end of the reference range compared with lower doses of levothyroxine that maintain a TSH level just above the upper limit of the reference range. Our overall goal is to determine the clinical consequences that allowing greater flexibility in levothyroxine dosing would have in older individuals who take levothyroxine. We propose to perform a randomized, double-blind clinical trial of two 6-month dosing strategies of levothyroxine in patients aged 65 years and older who are already taking a stable dose of levothyroxine therapy, one to maintain a target TSH of 0.5-2.0 mU/L and another of a lower levothyroxine dose to achieve a target TSH of 5.5-7.0 mU/L. We will assess the effects of levothyroxine therapy at two different TSH targets on symptoms of hypothyroidism, mood, sleep, measures of memory and executive function, weight, lipids, and a marker of bone turnover. This clinical trial will provide essential data to inform the clinical value of increased flexibility in LT4 dosing for older LT4 users. Implications include widening the LT4 therapeutic window, decreasing the frequency of LT4 titration and TSH testing, and reducing the risk of LT4 overtreatment. In sum, this study could transform treatment of hypothyroidism into an easier, safer, and less costly clinical practice for millions of older adults.

项目摘要 大约10%的美国65岁以上的成年人服用左旋甲状腺素治疗甲状腺功能减退症。指导 因为它的管理对数百万人的健康和医疗保健支出有着巨大而重要的影响 of older老people.左旋甲状腺素具有狭窄的治疗指数，需要通过以下方式监测给药： 促甲状腺激素（TSH）检测。目前的TSH参考范围是基于人群 尽管有证据表明，随着年龄的增长，妇女的比例会向更高的水平转变，但妇女的年龄分布仍然较年轻。此外，委员会认为， 观察数据并没有证明，如果TSH水平略高于 参考范围内的人不接受治疗，一项针对65岁或65岁以上人群的大型临床试验显示， 用左旋甲状腺素治疗这组患者。亚临床甲状腺功能减退症的治疗试验 低剂量的左旋甲状腺素，因为潜在的内源性甲状腺功能。这些数据可能不是 可推广到没有内源性甲状腺功能，完全依赖外源性 左旋甲状腺素在服用左旋甲状腺素的年轻人中进行的小型试验表明， 维持TSH水平在参考值下限的较高剂量左旋甲状腺素之间的差异 与维持TSH水平略高于上限的低剂量左旋甲状腺素相比， 参考范围我们的总体目标是确定允许更大灵活性的临床结果， 服用左旋甲状腺素的老年人中，我们建议执行一项 两种6个月左旋甲状腺素给药策略在65岁患者中的随机、双盲临床试验 已经服用稳定剂量的左旋甲状腺素治疗的30岁及以上患者，其中一种维持目标TSH为 0.5-2.0 mU/L和另一个较低的左旋甲状腺素剂量，以实现5.5-7.0 mU/L的目标TSH。我们将 评估在两种不同的TSH目标下左旋甲状腺素治疗对甲状腺功能减退症症状，情绪， 睡眠，记忆和执行功能的测量，体重，血脂和骨转换的标志物。本临床 试验将提供基本数据，以告知老年LT 4患者LT 4给药灵活性增加的临床价值 用户.其意义包括拓宽LT 4治疗窗，降低LT 4滴定频率， TSH检测，并降低LT 4过度治疗的风险。总之，这项研究可以改变治疗 将甲状腺功能减退症转化为更容易，更安全，更便宜的临床实践，为数百万老年人提供服务。