亚临床甲状腺功能减退症的脂代谢：左甲状腺素治疗前后甘油三酯丰富的脂蛋白的血浆动力学和向高密度脂蛋白的脂质转移。

Lipid metabolism in subclinical hypothyroidism: plasma kinetics of triglyceride-rich lipoproteins and lipid transfers to high-density lipoprotein before and after levothyroxine treatment.

机构信息

Medical School Hospital, University of São Paulo, São Paulo, Brazil.

出版信息

Thyroid. 2011 Apr;21(4):347-53. doi: 10.1089/thy.2010.0313.

DOI:10.1089/thy.2010.0313

PMID:21385074

Abstract

BACKGROUND

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis, but the abnormalities in plasma lipids that can contribute to atherogenesis are not prominent. The aim of this study was to test the hypothesis that patients with normocholesterolemic, normotriglyceridemic SCH display abnormalities in plasma lipid metabolism not detected in routine laboratory tests including abnormalities in the intravascular metabolism of triglyceride-rich lipoproteins, lipid transfers to high-density lipoprotein (HDL), and paraoxonase 1 activity. The impact of levothyroxine (LT4) treatment and euthyroidism in these parameters was also tested.

METHODS

The study included 12 SCH women and 10 matched controls. Plasma kinetics of an artificial triglyceride-rich emulsion labeled with radioactive triglycerides and cholesteryl esters as well as in vitro transfer of four lipids from an artificial donor nanoemulsion to HDL were determined at baseline in both groups and after 4 months of euthyroidism in the SCH group.

RESULTS

Fractional clearance rates of triglycerides (SCH 0.035 ± 0.016 min⁻¹, controls 0.029 ± 0.013 min⁻¹, p = 0.336) and cholesteryl esters (SCH 0.009 ± 0.007 min⁻¹, controls 0.009 ± 0.009 min⁻¹, p = 0.906) were equal in SCH and controls and were unchanged by LT4 treatment and euthyroidism in patients with SCH, suggesting that lipolysis and remnant removal of triglyceride-rich lipoproteins were normal. Transfer of triglycerides to HDL (SCH 3.6 ± 0.48%, controls 4.7 ± 0.63%, p = 0.001) and phospholipids (SCH 16.2 ± 3.58%, controls 21.2 ± 3.32%, p = 0.004) was reduced when compared with controls. After LT4 treatment, transfers increased and achieved normal values. Transfer of free and esterified cholesterol to HDL, HDL particle size, and paraoxonase 1 activity were similar to controls and were unchanged by treatment.

CONCLUSIONS

Although intravascular metabolism of triglyceride-rich lipoproteins was normal, patients with SCH showed abnormalities in HDL metabolism that were reversed by LT4 treatment and achievement of euthyroidism

摘要

背景

亚临床甲状腺功能减退症（SCH）与动脉粥样硬化有关，但导致动脉粥样硬化形成的血浆脂质异常并不明显。本研究旨在验证以下假说，即患有正常胆固醇、正常甘油三酯的 SCH 患者的血浆脂质代谢存在异常，这些异常在常规实验室检查中无法检测到，包括富含甘油三酯脂蛋白的血管内代谢、脂质向高密度脂蛋白（HDL）的转移以及对氧磷酶 1 活性的异常。还测试了左甲状腺素（LT4）治疗和甲状腺功能正常对这些参数的影响。

方法

本研究纳入了 12 名 SCH 女性和 10 名匹配的对照者。在两组中，均在基线时测定了人工富含甘油三酯乳液的放射性甘油三酯和胆固醇酯的血浆动力学，以及来自人工供体纳米乳液的四种脂质向 HDL 的体外转移，并在 SCH 组接受 4 个月的甲状腺功能正常治疗后进行测定。

结果

SCH 组的甘油三酯（SCH 0.035 ± 0.016 min⁻¹，对照组 0.029 ± 0.013 min⁻¹，p = 0.336）和胆固醇酯（SCH 0.009 ± 0.007 min⁻¹，对照组 0.009 ± 0.009 min⁻¹，p = 0.906）的清除率分数相等，且 LT4 治疗和 SCH 患者的甲状腺功能正常并未改变，提示富含甘油三酯脂蛋白的脂肪分解和残基清除正常。与对照组相比，甘油三酯（SCH 3.6 ± 0.48%，对照组 4.7 ± 0.63%，p = 0.001）和磷脂（SCH 16.2 ± 3.58%，对照组 21.2 ± 3.32%，p = 0.004）向 HDL 的转移减少。LT4 治疗后，转移增加并达到正常水平。游离胆固醇和酯化胆固醇向 HDL 的转移、HDL 颗粒大小和对氧磷酶 1 活性与对照组相似，且不受治疗影响。