Data from: Systemic thyroid hormone status during levothyroxine therapy in hypothyroidism: a systematic review and meta-analysis

CONTEXT:
The standard of care for overt hypothyroidism is levothyroxine at doses that normalize serum TSH levels. Whether this approach universally restores thyroid hormone signaling is unknown.

OBJECTIVE:
To review studies of overt hypothyroidism in which participants were treated with levothyroxine to normalize serum TSH levels and measured other objective markers of thyroid hormone signaling.

DESIGN:
Databases were searched for studies that reported objective markers of thyroid hormone signaling (serum low-density lipoprotein (LDL), total cholesterol (TC), sex hormone-binding globulin (SHBG), creatine kinase and/or ferritin levels; cognition, energy expenditure, and/or renal function) in levothyroxine monotherapy for overt, primary hypothyroidism among nonpregnant adults with normal serum TSH levels. For studies with LDL, TC and SHBG outcomes, data were pooled using random effects meta-analysis.

RESULTS:
A total of 99 studies met inclusion criteria, including 65 that reported serum cholesterol data. Meta-analysis showed that levothyroxine-treated hypothyroid participants with normal serum TSH levels had 3.31 ± 1.64 mg/dL higher serum LDL levels (p=0.044) and 9.60 ± 3.55 mg/dL higher serum TC levels (p=0.007) compared to controls. In studies that did not concomitantly assess healthy controls, serum LDL levels were 138.3 ± 4.6 mg/dL (p<0.001) and serum TC levels were 209.6 ± 3.4 mg/dL (p<0.001). Meta-analysis of 2 studies showed no significant difference between SHBG levels of levothyroxine-treated participants and controls.

CONCLUSIONS:
In studies that utilized levothyroxine monotherapy at doses that normalized the serum TSH for overt, primary hypothyroidism, not all systemic biological markers of thyroid hormone signaling were normalized, including serum LDL and TC levels.

CONTEXT:
显性甲状腺功能减退症的标准治疗方案为采用左甲状腺素（levothyroxine）治疗，以将血清促甲状腺激素（TSH）水平恢复至正常范围。但该治疗方案是否能全面恢复甲状腺激素信号传导，目前尚不明确。

OBJECTIVE:
本研究旨在回顾针对显性甲状腺功能减退症的相关研究，此类研究中受试者均接受左甲状腺素治疗以将血清TSH水平恢复至正常范围，并检测了其他甲状腺激素信号传导的客观标志物。

DESIGN:
本研究检索了相关数据库，纳入在非妊娠成人显性原发性甲状腺功能减退症患者中开展的、采用左甲状腺素单药治疗且血清TSH水平正常的研究，这些研究需报告甲状腺激素信号传导的客观标志物，包括血清低密度脂蛋白（low-density lipoprotein, LDL）、总胆固醇（total cholesterol, TC）、性激素结合球蛋白（sex hormone-binding globulin, SHBG）、肌酸激酶和/或铁蛋白水平；以及认知功能、能量消耗和/或肾功能。针对报告了LDL、TC及SHBG结局的研究，采用随机效应荟萃分析对数据进行合并。

RESULTS:
最终共有99项研究符合纳入标准，其中65项报告了血清胆固醇相关数据。荟萃分析结果显示，与对照组相比，经左甲状腺素治疗且血清TSH水平正常的甲状腺功能减退症受试者的血清LDL水平高3.31±1.64 mg/dL（p=0.044），血清TC水平高9.60±3.55 mg/dL（p=0.007）。在未同步设置健康对照的研究中，受试者血清LDL水平为138.3±4.6 mg/dL（p<0.001），血清TC水平为209.6±3.4 mg/dL（p<0.001）。对2项研究的荟萃分析显示，左甲状腺素治疗受试者与对照组的SHBG水平无显著差异。

CONCLUSIONS:
针对采用左甲状腺素单药治疗、将血清TSH水平恢复至正常范围的显性原发性甲状腺功能减退症患者的研究表明，并非所有甲状腺激素信号传导的全身生物学标志物均能恢复至正常水平，其中包括血清LDL及TC水平。