Levothyroxine Dosing in Older Individuals

项目总结 大约10%的65岁或65岁以上的美国成年人服用左旋甲状腺素来治疗甲状腺功能减退。导向 因为它的管理对数百万人的健康和医疗保健支出具有广泛而重要的影响 年长的人。左旋甲状腺素的治疗指标很窄，需要监测剂量。 促甲状腺激素(TSH)检测。目前的TSH参考范围是基于人口 年轻人的分布，尽管有证据表明随着年龄的增长有向更高水平转移的证据。此外， 观察数据显示，如果TSH水平略高于 参考范围没有得到治疗，一项针对65岁或65岁以上人群的大型临床试验没有显示出任何好处 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尝试 低剂量的左旋甲状腺素是因为潜在的内源性甲状腺功能。这些数据可能不是 适用于没有内源性甲状腺功能和完全依赖外源性甲状腺功能的个人 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，没有生理上的 将TSH水平维持在参考值下限的较高剂量左旋甲状腺素之间的差异 与较低剂量的左旋甲状腺素相比，左旋甲状腺素的TSH水平仅略高于 参考范围。我们的总体目标是确定允许更大的灵活性的临床后果 服用左旋甲状腺素的老年人服用左旋甲状腺素会有效果。我们建议执行一项 两种左旋甲状腺素6个月给药策略对65岁患者的随机双盲临床试验 已经在接受稳定剂量的左旋甲状腺素治疗的人，其中一种是维持TSH的目标 0.5-2.0mU/L和另一个较低剂量的左旋甲状腺素，以达到5.5mU/L-7.0mU/L的目标TSH。 评估两种不同TSH靶点的左旋甲状腺素治疗对甲状腺功能减退症状、情绪、 睡眠，记忆和执行功能的测量，体重，血脂，以及骨骼转换的标志。这个诊所 试验将提供必要的数据，以告知LT4剂量对较老的LT4的灵活性增加的临床价值 用户。其影响包括扩大LT4治疗窗口，降低LT4滴定频率和 TSH检测，并降低LT4过度治疗的风险。总而言之，这项研究可以改变对 为数百万老年人提供更容易、更安全、成本更低的甲状腺功能减退临床实践。

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.