From the Academic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences (D.J.S., K.H., P.L., M. McDade, T.J.Q.), the Robertson Centre for Biostatistics, Institute of Health and Wellbeing (I.F., S.K., A.M., M. Messow, R.W.), and the Institute of Cardiovascular and Medical Sciences (N.S.), University of Glasgow, Glasgow, and Care of the Elderly-Rehabilitation, Monklands Hospital, NHS Lanarkshire, Airdrie (G.E.) - all in the United Kingdom; the Department of General Internal Medicine, Inselspital, Bern University Hospital (N.R., C.E.A., D.A., C.B., M.R.B., M.F., C.F., D.K., H.A.V.D.), and the Institute of Primary Health Care (N.R., M.F.), University of Bern, Bern, and the Service of Endocrinology, Diabetes, and Metabolism, University Hospital of Lausanne, Lausanne (T.-H.C.) - all in Switzerland; the Department of Epidemiology and Public Health (P.M.K., J.P.B., C.H., G.M., A.O., D.O., C.S., K.A.W., E.K.W.), the Pharmaceutical Care Research Group, School of Pharmacy (S.B., M.K., K.A.W.), the School of Nursing and Midwifery (V.M.), and the Department of General Practice (A.R., E.K.W.), University College Cork, and the Health Research Board Clinical Research Facility, Mercy University Hospital (M.K.) - all in Cork, Ireland; the Department of Public Health and Center for Healthy Aging, University of Copenhagen (R.G.J.W.), and the Department of Medical Endocrinology, Copenhagen University Hospital Rigshospitalet (T.W.), Copenhagen, and the Department of Internal Medicine, Copenhagen University Hospital Herlev, Herlev (T.W.) - all in Denmark; the Departments of Gerontology and Geriatrics (S.P.M.), Internal Medicine (O.M.D.), Clinical Epidemiology (O.M.D.), Clinical Chemistry and Laboratory Medicine (W.P.J.E.), Public Health and Primary Care (R.S.D.P., R.K.E.P., J.G.), and Cardiology (J.W.J.), Leiden University Medical Center, and the Institute for Evidence-based Medicine in Old Age (S.P.M.), Leiden, and Radboud University Medical Center, Nijmegen (J.W.A.S.) - all in the Netherlands; and the Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco (D.C.B.).
N Engl J Med. 2017 Jun 29;376(26):2534-2544. doi: 10.1056/NEJMoa1603825. Epub 2017 Apr 3.
The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition.
We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points).
The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest.
Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).
用左甲状腺素治疗亚临床甲状腺功能减退症存在争议。我们旨在确定左甲状腺素治疗此类老年患者是否具有临床益处。
我们进行了一项双盲、随机、安慰剂对照、平行组试验，纳入了 737 名年龄至少 65 岁且持续存在亚临床甲状腺功能减退症（促甲状腺激素水平为 4.60 至 19.99 mIU/L；游离甲状腺素水平在参考范围内）的成年人。368 名患者被分配接受左甲状腺素（起始剂量为 50μg/天，如果体重<50kg 或患者患有冠心病，则为 25μg/天），根据促甲状腺激素水平调整剂量；369 名患者接受安慰剂并模拟剂量调整。两个主要结局为：1 年时甲状腺相关生活质量问卷中甲状腺症状评分和疲劳评分的变化（每个量表的范围为 0 至 100，得分越高表示症状或疲劳越严重；最小临床重要差异为 9 分）。
患者的平均年龄为 74.4 岁，396 名患者（53.7%）为女性。基线时平均（±SD）促甲状腺激素水平为 6.40±2.01 mIU/L；与安慰剂组相比，1 年后，左甲状腺素组的促甲状腺激素水平降至 5.48 mIU/L（P<0.001），中位剂量为 50μg。我们发现，1 年时甲状腺症状评分的平均变化无差异（安慰剂组为 0.2±15.3，左甲状腺素组为 0.2±14.4；组间差异，0.0；95%置信区间[CI]，-2.0 至 2.1）或疲劳评分（分别为 3.2±17.7 和 3.8±18.4；组间差异，0.4；95%CI，-2.1 至 2.9）。左甲状腺素对次要结局指标没有明显的有益影响。没有出现预先指定的特别关注的严重不良事件的明显增加。
左甲状腺素对亚临床甲状腺功能减退的老年患者没有明显益处。（由欧盟 FP7 等资助；TRUST 临床试验.gov 编号，NCT01660126）。
