甲状腺激素治疗对老年亚临床甲状腺功能减退症患者动脉粥样硬化的影响：一项随机试验。

Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial.

机构信息

Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Cardiology Division, University Hospital of Geneva, University of Geneva, Geneva, Switzerland.

出版信息

J Clin Endocrinol Metab. 2018 Aug 1;103(8):2988-2997. doi: 10.1210/jc.2018-00279.

DOI:10.1210/jc.2018-00279

PMID:29846630

Abstract

CONTEXT

Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist.

OBJECTIVE

To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis.

DESIGN AND SETTING

Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial.

PARTICIPANTS

Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range].

INTERVENTION

Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations.

MAIN OUTCOME MEASURES

Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound.

RESULTS

One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, -0.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference -0.03; 95% CI, -0.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14).

CONCLUSION

Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.

摘要

背景

亚临床甲状腺功能减退症（SHypo）与动脉粥样硬化有关，但目前尚无评估左甲状腺素对颈动脉粥样硬化影响的明确临床试验。

目的

评估用左甲状腺素治疗 SHypo 对颈动脉粥样硬化的影响。

设计和设置

在甲状腺激素替代治疗亚临床甲状腺功能减退症试验内嵌套的随机、双盲、安慰剂对照试验。

参与者

年龄≥65 岁、SHypo[促甲状腺激素（TSH），4.60 至 19.99 mIU/L；游离甲状腺素水平在参考范围内]的参与者。

干预措施

左甲状腺素剂量滴定以实现 TSH 正常化或安慰剂，包括模拟滴定。

主要观察指标

颈动脉内膜中层厚度（CIMT），用超声测量的最大斑块厚度。

结果

185 名参与者（平均年龄 74.1 岁，47%为女性，96 名随机分配至左甲状腺素组）接受了颈动脉超声检查。总体平均 TSH ± SD 为基线时的 6.35 ± 1.95 mIU/L，用左甲状腺素治疗后降至 3.55 ± 2.14 mIU/L，而安慰剂组为 5.29 ± 2.21 mIU/L（P < 0.001）。中位治疗 18.4 个月（四分位间距 12.2 至 30.0 个月）后，左甲状腺素组 CIMT 平均值为 0.85 ± 0.14mm，安慰剂组为 0.82 ± 0.13mm[组间差异=0.02mm；95%CI，-0.01 至 0.06；P=0.30]。颈动脉斑块比例相似（n=135；左甲状腺素组 70.8%，安慰剂组 75.3%；P=0.46）。左甲状腺素组最大颈动脉斑块厚度为 2.38 ± 0.92mm，安慰剂组为 2.37 ± 0.91mm（组间差异-0.03；95%CI，-0.34 至 0.29；P=0.86）。根据性别、基线 TSH（类别 4.6 至 6.9、7.0 至 9.9 和≥10 mIU/L）或已确立的心血管疾病，左甲状腺素治疗与平均 CIMT 之间均无显著交互作用（所有交互作用 P 值均≥0.14）。