發(fā)布時(shí)間：2018-05-13 11:46

  本文選題：自然轉(zhuǎn)歸 + 亞臨床甲狀腺功能減退��； 參考：《山東大學(xué)》2017年碩士論文

【摘要】：研究背景:當(dāng)病人的血清促甲狀腺素(thyroid-stimulating hormone,TSH)水平超過參考值范圍同時(shí)合并游離甲狀腺素(free thyroxine,FT4)血清濃度正常時(shí),我們常診斷其為亞臨床甲狀腺功能減退癥(subcl ini cal hypothyroidism,SCH)。這是一種全球性的高患病率疾病。SCH可以根據(jù)血清TSH水平分為輕度和重度。SCH的自然轉(zhuǎn)歸情況在不同的人群研究中有所波動(dòng)。年齡、性別、基線的TSH水平以及甲狀腺過氧化物酶抗體(thyroid peroxidase antibodies,TPOAb)水平都有可能影響甲狀腺功能的轉(zhuǎn)歸。然而,輕度SCH的自然轉(zhuǎn)歸還并不清楚。SCH有包括心血管風(fēng)險(xiǎn)增加、認(rèn)知能力下降等多方面的臨床危害。目前關(guān)于重度SCH的治療已有共識(shí),然而輕度SCH的治療策略還存在爭議。說到底,這是因?yàn)檩p度SCH可能出現(xiàn)的后果——或者說治療所能獲得的收益還不明確。這就更加迫切的需要了解輕度SCH的自然轉(zhuǎn)歸,從而為治療策略的制定提供參考。因此,我們開展了此研究,從而了解在我國年齡大于等于40的人群中輕度SCH的自然轉(zhuǎn)歸,并試圖發(fā)現(xiàn)一些易于監(jiān)測的預(yù)測因子。之后,考慮到SCH、血脂異常、心血管疾病3者問的密切聯(lián)系,我們進(jìn)一步通過meta分析了解左旋甲狀腺素(levothyroxine,L-T4)對(duì)SCH病人血脂的效應(yīng)。方法:1研究對(duì)象本研究的第一部分是一個(gè)前瞻性的、基于社區(qū)的隊(duì)列研究。研究對(duì)象均來自REACTION項(xiàng)目。共有11000例對(duì)象參加了篩查,最后共有505名輕度SCH病例完成了整個(gè)隨訪并被納入了我們后續(xù)的分析中。第二部分為納入了 12篇文獻(xiàn)的系統(tǒng)綜述。2資料收集收集病人的身高、體重、血壓、病史。無糖尿病病史的病人進(jìn)行口服葡萄糖耐量試驗(yàn)。測定TSH、游離三碘甲狀腺原氨酸(free triiodothyronine,FT3)、FT4、TPOAb、總膽固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白膽固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白膽固醇(low-density lipoprotein cholesterol,LDL-C)和谷草轉(zhuǎn)氨酶(aspartate aminotransferase,AST)、谷丙轉(zhuǎn)氨酶(alanine aminotransferase,ALT)和肌酐(creatinine,CR)。3統(tǒng)計(jì)分析流行病學(xué)數(shù)據(jù)統(tǒng)計(jì)分析過程均使用SPSS軟件進(jìn)行,meta分析均使用STATA軟件進(jìn)行。我們應(yīng)用多元Logistic回歸模型來分析影響SCH轉(zhuǎn)歸至臨床甲減或者正常甲功的指標(biāo)。Meta分析采用隨機(jī)效應(yīng)模型,并進(jìn)行了發(fā)表偏倚檢驗(yàn)、異質(zhì)性檢驗(yàn)、亞組分析和meta回歸。結(jié)果:1.1輕度SCH的患病率和轉(zhuǎn)歸在505名被納入分析的病人中,最后隨訪時(shí)有43.8%(n=221)仍為持續(xù)的SCH,而有49.7%(n=251)的病人甲狀腺功能恢復(fù)了正常,而有3.4%(n=17)的病人進(jìn)展成了臨床甲減。另外有12例對(duì)象甲功的轉(zhuǎn)歸不在本次分析的范圍,其中包括1例臨床甲亢,12例單純低FT4血癥和3例單純高FT4血癥。1.2基線數(shù)據(jù)我們根據(jù)隨訪結(jié)局的甲功轉(zhuǎn)歸將研究對(duì)象分成了 3組(甲功正常組、SCH組和臨床甲減組)。相比最后甲功恢復(fù)正常的對(duì)象,持續(xù)SCH的對(duì)象在基線時(shí)的年齡明顯更大,TSH明顯較高,而FT3和FT4都明顯較低。除此之外,進(jìn)展為臨床甲減的對(duì)象相比甲功恢復(fù)正常的對(duì)象TSH也明顯較高,而FT4水平比其余兩組都明顯較低,TPOAb陽性率比其他兩組都明顯更高。1.3回歸分析輕度SCH的病人若在基線時(shí)血清TC水平處于5.20-6.20 mmol/L或者高于6.20 mmol/L,則他們相比血清TC小于5.20mmol/L的對(duì)象進(jìn)展為臨床甲減的風(fēng)險(xiǎn)要分別升高 5 倍和 14 倍(0R =5.769,p =0.048 以及 0R =15.676,p =0.006)。同樣的,基線時(shí)血TPOAb陽性的對(duì)象相比陰性的對(duì)象進(jìn)展至臨床甲減的風(fēng)險(xiǎn)提高了 7 倍(OR =7.007,p =0.009)。另一方面,基線時(shí)年齡大于60歲的病人相比年齡小于50歲的病人甲功恢復(fù)正常的可能性只有后者的一半左右(OR =0.487,p =0.012)。在基線時(shí)CR處于第3四分位數(shù)組以及第4四分位數(shù)組的對(duì)象甲功恢復(fù)至正常的機(jī)會(huì)相比第1四分位數(shù)組的對(duì)象分別只其有50%和30%左右(OR =0.529,p =0.031以及OR =0.350,p =0.004)。基線時(shí)TSH大于等于7 mIU/L的對(duì)象轉(zhuǎn)歸至正常甲功的機(jī)會(huì)只有TSH小于 7mIU/L 的對(duì)象的 18%(OR =0.192,p0.001)。2 Meta分析共有12項(xiàng)研究,包含940名對(duì)象被納入了分析。相比對(duì)照組,L-T4顯著降低了 TC(-0.29,[-0.42 to-0.16])和 LDL-C(-0.22,[-0.36 to-0.09]),然而對(duì)HDL-C和TG沒有明顯效應(yīng)。在輕度亞臨床甲狀腺功能減退癥病人中的結(jié)果與總體病人無顯著差異。在長期治療中(6個(gè)月),L-T4降脂效果相比短期治療(≤6 個(gè)月)下降(TC:-0.19 對(duì)-0.50,p=0.047;LDL-C:-0.09 對(duì)-0.46,p=0.006)。結(jié)論:1.我們的研究說明將近有一半的輕度SCH病人會(huì)恢復(fù)正常甲功。并且在輕度SCH的病人中,基線陽性的TPOAb和較高水平的TC都與甲功的進(jìn)展風(fēng)險(xiǎn)正相關(guān),而高水平的TSH和CR與甲功的好轉(zhuǎn)幾率負(fù)相關(guān)。我們的結(jié)果提示血清TC和CR在SCH轉(zhuǎn)歸中的預(yù)測作用和可能存在的機(jī)制影響,尤其是TC在甲功惡化中的作用。2.L-T4在SCH人中有明確的降低TC和LDL-C的效應(yīng),在輕度SCH病人中該效果仍然存在。
[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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R581.2

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