本文選題：Graves病 + 抗甲狀腺藥物��； 參考：《大連醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:抗甲狀腺藥物(antithyroid drug,ATD)治療是Graves病(GD)的主要治療方法之一,2011年ATA/AACE(American Thyroid Association/American Association of the Clinical Endocrinologists)新指南推薦,ATD治療初始劑量為甲巰咪唑(MMI)10~20mg/d或丙硫氧嘧啶(PTU)150~450mg/d(分3次口服),但在合適的初始劑量等用藥方面仍缺乏有力的詢證醫(yī)學(xué)支持。同時(shí),針對(duì)GD患者在服用抗甲狀腺藥物治療過(guò)程中出現(xiàn)低甲狀腺素血癥(低T4血癥,hypothyroxinemia)的現(xiàn)象,對(duì)抗甲狀腺藥物治療GD引發(fā)的低T4血癥狀態(tài)進(jìn)行相關(guān)因素分析,進(jìn)而探討GD治療過(guò)程中聯(lián)用左旋甲狀腺素(L-T4)與否對(duì)病程的影響。目前GD的治療很不規(guī)范,具有很大的隨意性,治療過(guò)程中聯(lián)用L-T4與否對(duì)病程的影響尚無(wú)定論,很多內(nèi)分泌科醫(yī)生在臨床上往往根據(jù)其自身經(jīng)驗(yàn)或隨潮流加用或不加用L-T4。本研究通過(guò)前瞻性觀察不同劑量MMI用藥前及用藥后療效及其與發(fā)生低T4血癥間的關(guān)系,比較使用小劑量(MMI15mg/日)、中等劑量(MMI20mg/日)和大劑量(MMI130mg/日)甲巰咪唑治療GD的有效性和安全性,以及通過(guò)觀察聯(lián)用L-T4與否對(duì)GD的緩解率,為指導(dǎo)臨床用藥提供參考。實(shí)驗(yàn)對(duì)象與方法:選擇2013年5月至2014年9月就診于大連醫(yī)科大學(xué)附屬第一醫(yī)院一部門(mén)診的初發(fā)甲亢患者,依據(jù)患者臨床癥狀、查體、甲狀腺功能、促甲狀腺激素受體抗體(thyrotrophin receptor antibody,TRAb)及甲狀腺靜態(tài)顯像(ECT)檢查明確診斷為GD患者,依據(jù)納入及排除標(biāo)準(zhǔn),共納入146例患者。記錄其性別、年齡、癥狀,用藥前促甲狀腺激素(thyroid stimulating hormone,TSH)、FT3、FT4、TRAb、TgAb、TPOAb、生化肝功、白細(xì)胞及中性粒細(xì)胞絕對(duì)數(shù)值。將146例患者中FT440pmol/L者給予MMI15mg/d,即MMI15mg組(小劑量組,n=60);ft4介于40~60pmol/l者給予mmi20mg/d,即mmi20mg組(中等劑量組,n=39);ft460pmol/l者給予mmi30mg/d,即mmi30組(大劑量組,n=47)。對(duì)治療前合并輕度粒細(xì)胞減少(中性粒細(xì)胞數(shù)介于1.5×109/l~2.0×109/l)或存在輕度肝功能異常(alt或ast升高但未達(dá)到正常值的2.5倍)者,不論初始ft4水平如何,均給予mmi15mg/d。并按初治期、減量期、維持期規(guī)范用藥,每2周隨訪一次,至少隨訪16周,治療前后收集患者的一般資料、甲狀腺功能、血常規(guī)、肝功能相關(guān)血液生化指標(biāo)。數(shù)據(jù)錄入采用excel2003軟件,統(tǒng)計(jì)處理應(yīng)用spss22.0軟件,計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,兩組間數(shù)據(jù)比較采用t檢驗(yàn),三組間數(shù)據(jù)比較采用方差分析,百分率比較采用x2檢驗(yàn),以“經(jīng)atd治療后是否出現(xiàn)低t4血癥”為因變量,以“性別、年齡、用藥前血ft4水平、trab、tgab、tpoab水平及mmi初始劑量”為自變量行多因素logistic回歸分析,分別以“ft4達(dá)標(biāo)所需時(shí)間”、“tsh達(dá)標(biāo)所需時(shí)間”為因變量,以“性別、年齡、用藥前血ft4水平、trab、tgab、tpoab水平、mmi初始劑量、是否聯(lián)用l-t4”為自變量行多元線性回歸分析,p0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1.三組不同劑量組mmi治療gd均能取得良好的效果,治療后ft4均比治療前顯著下降,差異具有統(tǒng)計(jì)學(xué)意義(p0.01);治療前三組組間ft4比較,mmi30mg組均高于mmi15mg組及mmi20mg組,差異有統(tǒng)計(jì)學(xué)意義(p0.01);治療后三組組間ft4比較,無(wú)統(tǒng)計(jì)學(xué)差異(p0.05);治療后mmi30mg組ft4下降的幅度明顯大于mmi15mg組及mmi20mg組(p0.01)。三組治療后tsh均比治療前有上升趨勢(shì),且mmi30mg組差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。2.以“經(jīng)atd治療后是否出現(xiàn)低t4血癥”為因變量,以“性別、年齡、用藥前血ft4水平、trab、tgab、tpoab水平及mmi初始劑量”為自變量行多因素logistic回歸分析,結(jié)果顯示低t4血癥發(fā)生與上述指標(biāo)均不相關(guān)(p0.05)。3.mmi治療16周過(guò)程中共有65例出現(xiàn)低t4血癥,其中聯(lián)用l-t4者23例,未聯(lián)用l-t4者42例,聯(lián)用l-t4組ft4達(dá)標(biāo)時(shí)間遲于未聯(lián)用l-t4組,但差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05)。聯(lián)用l-t4組低t4血癥達(dá)標(biāo)比例為65.22%,略高于不聯(lián)用l-t4組52.38%,兩組間比較采用x2檢驗(yàn),差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05)。4.TSH及FT4達(dá)標(biāo)所需時(shí)間三組組內(nèi)比較,FT4達(dá)標(biāo)時(shí)間均早于TSH達(dá)標(biāo)時(shí)間,且MMI15mg組差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。TSH達(dá)標(biāo)時(shí)間三組組間比較,MMI20mg組的TSH達(dá)標(biāo)時(shí)間最慢,其與MMI15mg組及MMI30mg組之間均存在顯著差異,差異有統(tǒng)計(jì)學(xué)意義(P0.05);15mg組與30mg組TSH達(dá)標(biāo)時(shí)間之間無(wú)顯著差異(P0.05)。而FT4達(dá)標(biāo)時(shí)間三組組間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。5.分別以“FT4達(dá)標(biāo)所需時(shí)間”、“TSH達(dá)標(biāo)所需時(shí)間”為因變量,以“性別、年齡、用藥前血FT4水平、TRAb、TgAb、TPOAb水平、MMI初始劑量、是否聯(lián)用L-T4”為自變量行多元線性回歸分析,結(jié)果顯示FT4達(dá)標(biāo)所需時(shí)間及TSH達(dá)標(biāo)所需時(shí)間與上述指標(biāo)均不相關(guān)(P0.05)。6.三組治療16周后共96例GD患者FT4降至正常,MMI15mg組FT4達(dá)標(biāo)比例為84.62%,高于MMI20mg組及MMI30mg組,但三組間比較采用x2檢驗(yàn),差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。FT4降至正常時(shí),此時(shí)TSH降至正常者16例,未完全正常者80例,其中,MMI15mg組TSH降至正常者9例,完全達(dá)標(biāo)比例為20.45%,高于MMI20mg組及MMI30mg組,但三組間比較采用x2檢驗(yàn),無(wú)顯著性差異(P0.05)。結(jié)論:1.根據(jù)初始FT4水平選擇不同劑量MMI治療,均可有效控制甲狀腺功能亢進(jìn)癥,不同劑量組間療效相似,其療效與劑量無(wú)關(guān)。2.低T4血癥發(fā)生與否與患者性別、年齡、用藥前血FT4水平、TRAb、Tg Ab、TPOAb水平及MMI初始劑量均不相關(guān)。3.低T4血癥發(fā)生時(shí)聯(lián)用L-T4沒(méi)有影響甲狀腺功能的恢復(fù),也沒(méi)有顯示出優(yōu)勢(shì)。
[Abstract]:Objective: antithyroid drug (ATD) is one of the main treatments for Graves disease (GD). In 2011, the new guidelines for ATA/AACE (American Thyroid Association/American Association of the) are recommended for the initial dose of methimidazole or Propyl Sulfide. 3 times of oral administration), but there is still a lack of strong evidence medical support in the appropriate initial dose. At the same time, the phenomenon of hypothyroidemia (hypothyroidemia, hypothyroxinemia) in the treatment of antithyroid drugs for GD patients and the related factors of the hypothyroidism caused by the treatment of thyroid drugs for GD induced by GD are carried out. The effect of combined use of levothyroxine (L-T4) on the course of disease during the treatment of GD is discussed. At present, the treatment of GD is not standardized and has great randomness. There is no definite conclusion on the influence of combined use of L-T4 on the course of disease in the treatment process. Many department of endocrinology doctors often use or do not add to their own experience or trend according to their own experience. The effect of different doses of MMI before and after drug use and its relationship with low T4 were prospectively observed. The efficacy and safety of small dose (MMI15mg/ day), medium dose (MMI20mg/ day) and large dose (MMI130mg/ day) methimazole in the treatment of GD were compared, and the remission of GD was observed by observing the combined use of L-T4 to the GD. Rate, to provide reference for guiding clinical medication. Experimental subjects and methods: selected patients with primary hyperthyroidism in an outpatient department of the First Affiliated Hospital of Dalian Medical University from May 2013 to September 2014. According to the clinical symptoms, examination, thyroid function, thyroid stimulating hormone receptor antibody (thyrotrophin receptor antibody, TRAb) and thyroid gland The static imaging (ECT) examination was clearly diagnosed as GD patients. According to the inclusion and exclusion criteria, 146 patients were included. The sex, age, symptoms, thyroid stimulating hormone (thyroid stimulating hormone, TSH), FT3, FT4, TRAb, TgAb, TgAb, TPOAb, biochemical liver work, and the absolute values of leukocyte and neutrophils were recorded in 146 patients. MMI15mg/d, MMI15mg group (small dose group, n=60), FT4 between 40~60pmol/l and mmi20mg group (medium dose group, n=39); ft460pmol/l was given to mmi30mg/d, that is, mmi30 group (large dose group, n=47). Mild granulocytic reduction (neutrophilic granulocyte count was 1.5 * * * * *) before treatment or mild liver function difference before treatment. Often (ALT or ast increased but not 2.5 times the normal value), regardless of the initial FT4 level, all of them were given mmi15mg/d. and according to the initial treatment period, the reduction period and the maintenance period, followed up every 2 weeks for at least 16 weeks. The general data of the patients, the thyroid gland function, blood routine, and the blood biochemical indexes related to liver function were collected before and after treatment. Using Excel2003 software, statistical processing and application of spss22.0 software, the measurement data were expressed with mean + standard deviation (x + s). The data of the two groups were compared with t test. The data of the three groups were compared by variance analysis, and the percentage was compared with x2 test. The result was "whether there was low T4 after ATD treatment" as the dependent variable and "sex, age, and blood ft before medication". The 4 level, TRAb, TGAb, TPOAb level and the initial dose of MMI "multiple factor Logistic regression analysis of the independent variables, respectively," the time required for the FT4 standard "," the time required for the TSH standard "as the dependent variable, with" sex, age, blood FT4 level before medication, TRAb, TGAb, TPOAb water level, MMI initial dose, whether or not to use "as the independent variable linear multivariate linear Regression analysis, P0.05 showed that the difference was statistically significant. Results: 1. three groups of different doses of MMI treatment GD can achieve good results, after treatment, FT4 was significantly lower than before treatment, the difference was statistically significant (P0.01); before the treatment of three groups of FT4, mmi30mg group was higher than the mmi15mg group and mmi20mg group, the difference was statistically significant (P0.01); After treatment, there was no significant difference in FT4 between the three groups (P0.05), and the decrease of FT4 in group mmi30mg was significantly greater than that in group mmi15mg and mmi20mg (P0.01). The TSH in the three groups had a higher trend than before the treatment, and the difference in the mmi30mg group was statistically significant (P0.05).2.. "Sex, age, blood FT4 level, TRAb, TGAb, TPOAb level and initial dose of MMI" were analyzed by multiple factor Logistic regression analysis of the independent variable. The results showed that there were 65 cases of low T4 anemia in the 16 week process of.3.mmi treatment of low T4 (P0.05), of which 23 cases were combined with L-T4, 42 cases were not combined with L-T4. The standard time of FT4 in group T4 was later than that of the non combined L-T4 group, but the difference was not statistically significant (P0.05). The proportion of the low T4 anemia in the L-T4 group was 65.22%, slightly higher than that of the non combined L-T4 group. The two groups were compared with the x2 test. The difference was not statistically significant (P0.05) in the three groups of.4.TSH and FT4. Time, and the difference in group MMI15mg was statistically significant (P0.01).TSH standard time between three groups, MMI20mg group TSH standard time was the slowest, and there was significant difference between group MMI15mg and MMI30mg group, the difference was statistically significant (P0.05); 15mg group and 30mg group TSH time between the standard time no significant difference (P0.05) and three groups of time standard time. There was no statistically significant difference between the groups (P0.05).5. as "time required for the standard of FT4" and "time required for the standard of TSH" as the dependent variable. "Sex, age, FT4 level of blood before medication, TRAb, TgAb, TPOAb level, MMI initial dose, or not with L-T4" was a multivariate linear regression analysis, and the results showed the time required for FT4 and T. The time required for the SH standard was not related to the above index (P0.05).6. three groups after 16 weeks of treatment, 96 cases of GD patients were reduced to normal FT4, MMI15mg group FT4 standard ratio was 84.62%, higher than the MMI20mg group and MMI30mg group, but the three groups were compared to x2 test, the difference was not statistically significant (P0.05) to normal, this time to 16 cases, not complete. 80 cases were normal, among which, 9 cases of MMI15mg group TSH were reduced to normal, the proportion of complete standard was 20.45%, higher than that of group MMI20mg and MMI30mg, but x2 test was used in the three groups, and there was no significant difference (P0.05). Conclusion: 1. according to the initial FT4 level, the choice of different doses of MMI therapy can effectively control the hyperthyroidism, the effect of different dosage groups is effective. Similarly, the efficacy and dose independent.2. hypothyroidemia was associated with patients' sex, age, blood FT4 levels, TRAb, Tg Ab, TPOAb level and initial dose of MMI, which did not affect the recovery of thyroid function, and did not show advantages.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R581.1

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