亚临床甲状腺功能减退的自然转归及左旋甲状腺素的降脂效应

发布时间：2018-05-13 11:46

本文选题：自然转归 + 亚临床甲状腺功能减退　；参考：《山东大学》2017年硕士论文

【摘要】：研究背景:当病人的血清促甲状腺素(thyroid-stimulating hormone,TSH)水平超过参考值范围同时合并游离甲状腺素(free thyroxine,FT4)血清浓度正常时,我们常诊断其为亚临床甲状腺功能减退症(subcl ini cal hypothyroidism,SCH)。这是一种全球性的高患病率疾病。SCH可以根据血清TSH水平分为轻度和重度。SCH的自然转归情况在不同的人群研究中有所波动。年龄、性别、基线的TSH水平以及甲状腺过氧化物酶抗体(thyroid peroxidase antibodies,TPOAb)水平都有可能影响甲状腺功能的转归。然而,轻度SCH的自然转归还并不清楚。SCH有包括心血管风险增加、认知能力下降等多方面的临床危害。目前关于重度SCH的治疗已有共识,然而轻度SCH的治疗策略还存在争议。说到底,这是因为轻度SCH可能出现的后果——或者说治疗所能获得的收益还不明确。这就更加迫切的需要了解轻度SCH的自然转归,从而为治疗策略的制定提供参考。因此,我们开展了此研究,从而了解在我国年龄大于等于40的人群中轻度SCH的自然转归,并试图发现一些易于监测的预测因子。之后,考虑到SCH、血脂异常、心血管疾病3者问的密切联系,我们进一步通过meta分析了解左旋甲状腺素(levothyroxine,L-T4)对SCH病人血脂的效应。方法:1研究对象本研究的第一部分是一个前瞻性的、基于社区的队列研究。研究对象均来自REACTION项目。共有11000例对象参加了筛查,最后共有505名轻度SCH病例完成了整个随访并被纳入了我们后续的分析中。第二部分为纳入了 12篇文献的系统综述。2资料收集收集病人的身高、体重、血压、病史。无糖尿病病史的病人进行口服葡萄糖耐量试验。测定TSH、游离三碘甲状腺原氨酸(free triiodothyronine,FT3)、FT4、TPOAb、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)和谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)和肌酐(creatinine,CR)。3统计分析流行病学数据统计分析过程均使用SPSS软件进行,meta分析均使用STATA软件进行。我们应用多元Logistic回归模型来分析影响SCH转归至临床甲减或者正常甲功的指标。Meta分析采用随机效应模型,并进行了发表偏倚检验、异质性检验、亚组分析和meta回归。结果:1.1轻度SCH的患病率和转归在505名被纳入分析的病人中,最后随访时有43.8%(n=221)仍为持续的SCH,而有49.7%(n=251)的病人甲状腺功能恢复了正常,而有3.4%(n=17)的病人进展成了临床甲减。另外有12例对象甲功的转归不在本次分析的范围,其中包括1例临床甲亢,12例单纯低FT4血症和3例单纯高FT4血症。1.2基线数据我们根据随访结局的甲功转归将研究对象分成了 3组(甲功正常组、SCH组和临床甲减组)。相比最后甲功恢复正常的对象,持续SCH的对象在基线时的年龄明显更大,TSH明显较高,而FT3和FT4都明显较低。除此之外,进展为临床甲减的对象相比甲功恢复正常的对象TSH也明显较高,而FT4水平比其余两组都明显较低,TPOAb阳性率比其他两组都明显更高。1.3回归分析轻度SCH的病人若在基线时血清TC水平处于5.20-6.20 mmol/L或者高于6.20 mmol/L,则他们相比血清TC小于5.20mmol/L的对象进展为临床甲减的风险要分别升高 5 倍和 14 倍(0R =5.769,p =0.048 以及 0R =15.676,p =0.006)。同样的,基线时血TPOAb阳性的对象相比阴性的对象进展至临床甲减的风险提高了 7 倍(OR =7.007,p =0.009)。另一方面,基线时年龄大于60岁的病人相比年龄小于50岁的病人甲功恢复正常的可能性只有后者的一半左右(OR =0.487,p =0.012)。在基线时CR处于第3四分位数组以及第4四分位数组的对象甲功恢复至正常的机会相比第1四分位数组的对象分别只其有50%和30%左右(OR =0.529,p =0.031以及OR =0.350,p =0.004)。基线时TSH大于等于7 mIU/L的对象转归至正常甲功的机会只有TSH小于 7mIU/L 的对象的 18%(OR =0.192,p0.001)。2 Meta分析共有12项研究,包含940名对象被纳入了分析。相比对照组,L-T4显著降低了 TC(-0.29,[-0.42 to-0.16])和 LDL-C(-0.22,[-0.36 to-0.09]),然而对HDL-C和TG没有明显效应。在轻度亚临床甲状腺功能减退症病人中的结果与总体病人无显著差异。在长期治疗中(6个月),L-T4降脂效果相比短期治疗(≤6 个月)下降(TC:-0.19 对-0.50,p=0.047;LDL-C:-0.09 对-0.46,p=0.006)。结论:1.我们的研究说明将近有一半的轻度SCH病人会恢复正常甲功。并且在轻度SCH的病人中,基线阳性的TPOAb和较高水平的TC都与甲功的进展风险正相关,而高水平的TSH和CR与甲功的好转几率负相关。我们的结果提示血清TC和CR在SCH转归中的预测作用和可能存在的机制影响,尤其是TC在甲功恶化中的作用。2.L-T4在SCH人中有明确的降低TC和LDL-C的效应,在轻度SCH病人中该效果仍然存在。
[Abstract]:Background: when the serum thyrotropin (thyroid-stimulating hormone, TSH) level of the patient exceeds the reference range and the serum concentration of free thyroxine (free thyroxine, FT4) is normal, we often diagnose it as subclinical hypothyroidism (subcl ini cal hypothyroidism, SCH). This is a global high risk. Disease rate disease.SCH can fluctuate in different population studies based on the natural outcome of mild and severe.SCH levels based on serum TSH levels. Age, sex, baseline TSH level and thyroid peroxidase antibody (thyroid peroxidase antibodies, TPOAb) levels may affect the outcome of thyroid function. However, mild SCH It is not clear that.SCH has many clinical hazards, including increased cardiovascular risk and cognitive decline. There is a consensus on the treatment of severe SCH, but the treatment strategy for mild SCH is still controversial. In the end, this is due to the possible subsequent fruits of the mild SCH - or the benefits of treatment. It is not clear. This is more urgent to understand the natural outcome of mild SCH, so as to provide reference for the formulation of therapeutic strategies. Therefore, we have carried out this study to understand the natural outcome of the mild SCH in the population of our country older than 40, and to try to find some predictors that are easily monitored. After that, we consider SCH, blood lipid differences. Often, the close link between the 3 subjects of cardiovascular disease, we further studied the effect of levothyroxine (L-T4) on blood lipids in SCH patients. Methods: the first part of this study was a prospective, community based cohort study. All of the subjects were from the REACTION project. There were 11000 subjects with a total of 11000 subjects. In addition, a total of 505 cases of mild SCH cases were followed up and included in our follow-up analysis. The second part was a systematic review of the.2 data collected in 12 documents to collect the patient's height, weight, blood pressure, and history. The oral glucose tolerance test for patients with no history of diabetes. Determination of TSH, free three iodine. Free triiodothyronine (FT3), FT4, TPOAb, total cholesterol (total cholesterol, TC), triglyceride (triglyceride, TG), high density lipoprotein cholesterol (high-density lipoprotein), low density lipoprotein cholesterol and glutamic pyruvic aminotransferase Ansferase, AST), alanine aminotransferase, ALT, and creatinine (creatinine, CR).3 statistical analysis of the statistical analysis of epidemiological data were performed using SPSS software. Meta analysis was carried out using STATA software. We used multiple Logistic regression models to analyze the fingers affecting the clinical hypothyroidism or normal thyroidism. A random effect model was used in the standard.Meta analysis, and a publication bias test, heterogeneity test, subgroup analysis and meta regression. Results: the prevalence and outcome of 1.1 mild SCH were found in 505 patients who were included in the analysis. At the last follow-up, 43.8% (n=221) continued to be SCH, while 49.7% (n=251) of the patients returned to normal thyroid function. 3.4% (n=17) patients progressed to clinical hypothyroidism. In addition, the outcome of 12 cases was not in the scope of this analysis, including 1 cases of clinical hyperthyroidism, 12 cases of simple hypoemia, and 3 cases of simple high FT4.1.2 baseline data. We divided the subjects into 3 groups according to the outcome of the follow-up (group A, SCH, and the normal group. In the clinical hypothyroidism group, the age of the last SCH was significantly higher in the baseline, and the TSH was significantly higher at the baseline, while the FT3 and FT4 were significantly lower. In addition, the TSH was significantly higher in the object of clinical hypothyroidism than in the target TSH, and the FT4 level was significantly lower than the other two groups, TPOAb Yang. The rate of sex was significantly higher than the other two groups..1.3 regression analysis of patients with mild SCH was 5 times and 14 times higher than those of serum TC less than 5.20mmol/L, if the serum TC level was 5.20-6.20 mmol/L or higher than 6.20 mmol/L at baseline. 6). Similarly, the risk of progressing to clinical hypothyroidism by TPOAb positive subjects at baseline was 7 times higher than that of clinical hypothyroidism (OR =7.007, P =0.009). On the other hand, patients older than 60 years of age were more than half of the latter (OR =0.487, P =0.012) at baseline (OR =0.487, P =0.012). When the CR is in the third four division array and the fourth four sub array of object armor work is restored to the normal opportunity compared to the first four partition array, only 50% and 30% (OR =0.529, P =0.031 and OR =0.350, P =0.004). At baseline, the opportunity for TSH greater than equal to 7 mIU/L to normal armour power is only less than TSH. The 18% (OR =0.192, p0.001).2 Meta analysis of a total of 12 studies, including 940 subjects included in the analysis. Compared to the control group, L-T4 significantly reduced TC (-0.29, [-0.42 to-0.16]) and LDL-C (-0.22,), but had no significant effects. The results and total in mild subclinical hypothyroidism patients There was no significant difference in the patient's body. In the long-term treatment (6 months), the effect of L-T4 lipid lowering was compared with short-term treatment (less than 6 months) (TC:-0.19 to -0.50, p=0.047; LDL-C:-0.09 against -0.46, p=0.006). 1. our study showed that nearly half of the mild SCH patients would restore normal thyroid work. And in mild SCH patients, the baseline positive TPOAb The higher level of TC and the higher levels of TSH and CR are negatively related to the improvement of the work. Our results suggest the predictive and possible mechanisms of the serum TC and CR in the SCH transfer, especially the role of TC in the deterioration of the thyroid function,.2.L-T4 reduces TC and LDL-C in SCH. Effect, the effect still exists in mild SCH patients.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R581.2

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