Lipid Changes in Thyroid Disease: The Effect of Thyroxine and Analogues
Lipid Changes in Thyroid Disease: The Effect of Thyroxine and Analogues
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甲状腺疾病中的脂质变化：甲状腺素及其类似物的作用
DOI：
10.1177/003591577406700740
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发表时间：
1974
影响因子：
17.3
通讯作者：
B. Tulloch
中科院分区：
文献类型：
--
作者：
B. Tulloch
甲状腺功能减退症与空腹血浆胆固醇（Peters & Mann 1943）和甘油三酯（Nikkilii & Kekki 1972，Tulloch et al. 1973）升高之间的关联引起了人们对甲状腺激素在脂质代谢中的作用及其在血管疾病和家族性高脂血症治疗中的作用的疑问。虽然空腹高胆固醇血症是甲状腺功能减退症的常见现象，但并非总是如此，但低胆固醇血症在甲状腺毒症中很少有诊断价值（Peters & Mann 1943）。在人类中，循环血浆胆固醇来源于肠道吸收或内源合成。胆固醇主要以粪便中性类固醇和胆盐的形式排泄。甲状腺素对胆固醇代谢的主要作用部位仍不清楚。甲状腺素缺陷大鼠的肝切片表现出乙酸盐合成胆固醇的速率降低，但甲羟戊酸作为前体的胆固醇合成正常（Fletcher & Myant 1958），表明甲状腺素可能影响胆固醇代谢的早期阶段，例如 HMG-CoAreductase（Gries 等人，1962）。粘液水肿患者显示 131I 标记的低密度脂蛋白 (LDL) 的周转减少，LDL 是血浆胆固醇的主要载体。甲状腺素治疗可使标记的 LDL 恢复正常（Walton 等，1965）。此外，甲状腺素治疗可增加中性类固醇和胆汁酸的粪便排泄，而不会显着影响血浆 14C-胆固醇比活性衰减曲线，这表明甲状腺素治疗粘液水肿主要导致胆固醇清除率的增加（Mettinen 1968）。空腹血浆甘油三酯水平升高通常伴随粘液水肿（Nikkila & Kekki 1972，Tulloch 等人 1973），饮食调整可能进一步影响血浆甘油三酯水平（Porte 等人 1966）。空腹血浆甘油三酯主要由血浆极低密度（VLDL 或前β）脂蛋白部分携带。循环脂蛋白中的甘油三酯的水解是由脂蛋白脂肪酶在毛细血管内皮附近的位点进行的，从而允许长链脂肪酸储存在组织中（Robinson & Wing 1970，Scow 等人 1972）。注射肝素后血浆中的脂蛋白脂肪酶活性已被用作组织脂肪分解活性的指标（Fredrickson 等，1967）。对粘液水肿中甘油三酯动力学的研究表明，外源性（Tulloch 等人，1973）和内源性标记的甘油三酯从循环中的清除率降低（Nikkila & Kekki，1972）。此类研究表明，粘液水肿中甘油三酯清除率主要受损。这些观察结果与低血浆肝素后脂肪分解活性相关（Kirkleby 1968），该活性在甲状腺素治疗后恢复正常（Tulloch 等人，1973）。在甲状腺毒症中，外源性甘油三酯的清除率增加，与多项研究中报道的肝素后低脂解活性形成鲜明对比（Kirkleby 1968、Arons 等人 1972、Tulloch 等人 1973）。这种差异在甲状腺素治疗的兔子中重现（Kirkleby 1968），并且可能与甲状腺素对肝素释放脂蛋白脂肪酶的某些方面的影响有关。甲状腺素改变脂肪细胞对儿茶酚胺脂肪分解作用的敏感性，而三碘甲状腺原氨酸本身可能具有脂肪分解作用（Krishna 等，1968）。对粘液水肿中血浆 FFA 的研究表明，FFA 水平和 14C 标记棕榈酸酯的周转率均降低（Tulloch 等，1973）。据报道，甲状腺毒症伴随的血浆 FFA 升高可能通过为肝脏 VLDL 合成提供增加的底物，导致内源性标记的甘油三酯的周转增加（Nikkila & Kekki 1972）。由于高胆固醇血症（Keys et al. 1963）和高甘油三酯血症（Carlson & Bottiger 1972）均构成危险因素，因此有人提出边缘性甲状腺功能减退症可能导致心血管疾病。 Basteine 等人在一项针对 400 名患有非甲状腺疾病的女性患者的研究中。 (1971)指出抗甲状腺抗体的发生率与心肌梗塞之间呈正相关。然而，其他对照研究不同意这一观点（Heinonen 等人，1972 年），对这一假设的更全面评估有待对亚临床甲状腺疾病和脂质代谢进行充分的流行病学调查（Evered 等人，1973 年）。
The association between hypothyroidism and raised fasting plasma levels of both cholesterol (Peters & Mann 1943) and triglyceride (Nikkilii & Kekki 1972, Tulloch et al. 1973) has raised questions both as to the role of thyroid hormones in lipid metabolism and their part in vascular disease and the treatment of familial hyperlipemic states. Whereas fasting hypercholesterolemia is a common, but not invariable finding in hypothyroidism, hypocholesterolemia is rarely of diagnostic value in thyrotoxicosis (Peters & Mann 1943). In man, the circulating plasma cholesterol originates from either gut absorption or endogenous synthesis. Cholesterol excretion occurs principally as faecal neutral steroids and bile salts. The major site of thyroxine action on cholesterol metabolism remains unclear. Liver slices from thyroxine-deficient rats exhibit a decreased rate of cholesterol synthesis from acetate, but normal synthesis from mevalonate as precursor (Fletcher & Myant 1958), suggesting thyroxine may affect an early stage in cholesterol metabolism, such as the enzyme HMG-CoAreductase (Gries et al. 1962). Myxcedematous patients show a decreased turnover of l31Ilabelled low-density lipoproteins (LDL), the principal carrier of plasma cholesterol. Treatment with thyroxine reverts the turnover of labelled LDL towards normal (Walton et al. 1965). Moreover, thyroxine treatment increases faecal excretion of neutral steroids and bile acids without significantly affecting plasma 14C-cholesterol specific activity decay curves, suggesting that thyroxine therapy in myxcedema leads predominantly to an increase in cholesterol clearance (Mettinen 1968). Increased fasting plasma triglyceride levels commonly accompany myxcedema (Nikkila & Kekki 1972, Tulloch et al. 1973), and dietary modification may further affect plasma triglyceride levels (Porte et al. 1966). Fasting plasma triglycerides are carried chiefly on the plasma very-low density (VLDL or pre-beta) lipoprotein fraction. Hydrolysis of triglyceride from circulating lipoprotein is carried out by the enzyme lipoprotein lipase at a site near the capillary endothelium, permitting long-chain fatty acid storage in tissues (Robinson & Wing 1970, Scow et al. 1972). Lipoprotein lipase activity in the plasma following injection of heparin has been used as an index of tissue lipolytic activity (Fredrickson et al. 1967). Studies on triglyceride kinetics in myxcedema have indicated a lowered fractional clearance of both exogenous (Tulloch et al. 1973) and endogenously labelled triglycerides from the circulation (Nikkila & Kekki 1972). Such studies would suggest predominantly impaired triglyceride clearance in myxcedema. These observations correlate with low plasma post-heparin lipolytic activity (Kirkleby 1968) which reverts towards normal following thyroxine therapy (Tulloch etal. 1973). In thyrotoxicosis, the fractional clearance of exogenous triglyceride is increased, and contrasts with the low post-heparin lipolytic activity reported in several studies (Kirkleby 1968, Arons et al. 1972, Tulloch et al. 1973). This discrepancy was reproduced in thyroxine-treated rabbits (Kirkleby 1968), and may relate to an effect of thyroxine on some aspect of the release of lipoprotein lipase by heparin. Thyroxine alters the adipocyte sensitivity to the lipolytic action of catecholamines, and triiodothyronine may itself be lipolytic (Krishna et al. 1968). Studies on plasma FFA in myxoedema show both decreased FFA levels and turnover of 14C-labelled palmitate (Tulloch et al. 1973). The raised plasma FFA reported accompanying thyrotoxicosis may, by providing increased substrate for hepatic VLDL synthesis, contribute to the increased turnover of endogenously labelled triglycerides (Nikkila & Kekki 1972). Since both hypercholesterolkmia (Keys et al. 1963) and hypertriglyceridwmia (Carlson & Bottiger 1972) constitute risk factors, the suggestion that borderline hypothyroidism may contribute to cardiovascular disease has been raised. In a study of 400 female patients admitted with nonthyroid conditions, Basteine et al. (1971) noted a positive correlation between the incidence of antithyroid antibodies and myocardial infarction. Other controlled studies disagree, however (Heinonen et al. 1972) and fuller evaluation of this hypothesis awaits an adequate epidemiological survey of subclinical thyroid disease and lipid metabolism (Evered et al. 1973).