本文選題：重組人生長(zhǎng)激素 + 促性腺激素釋放激素類似物�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文

【摘要】：背景和目的隨著社會(huì)的發(fā)展,國(guó)民經(jīng)濟(jì)水平的提高,人們?cè)絹?lái)越重視對(duì)美的追求,身高作為美的重要方面,也受到越來(lái)越多的關(guān)注。由于矮身材對(duì)患者的自尊、生活、工作和婚戀造成諸多影響,兒童和青春期矮身材患者及其家屬往往有強(qiáng)烈的改善身高的需求。應(yīng)用重組人生長(zhǎng)激素(rhGH)或聯(lián)用促性腺激素釋放激素類似物(GnRHa)治療兒童和青春期矮身材的療效尚有爭(zhēng)議;對(duì)治療過(guò)程中rhGH對(duì)糖代謝、脂代謝、甲狀腺功能等方面的影響研究不多,對(duì)rhGH聯(lián)合GnRHa治療矮身材過(guò)程中患者的代謝變化所知甚少。本文旨在分析兒童和青春發(fā)育初期的矮身材患者采用rhGH單用或rhGH聯(lián)合GnRHa治療的療效,以及治療過(guò)程中的代謝變化。對(duì)象和方法rhGH單用或rhGH聯(lián)合GnRHa治療的兒童及青春期矮身材患者共62例。青春發(fā)育前的患者采用rhGH單用治療;明顯青春發(fā)育的患者采用rhGH聯(lián)合GnRHa治療;部分青春發(fā)育剛啟動(dòng)的患者,臨床判斷其青春發(fā)育速度較慢,生長(zhǎng)潛力較大,結(jié)合患者及其家屬的意愿等因素,也采用了 rhGH單用治療。每隔3-6個(gè)月隨診一次,監(jiān)測(cè)身高、空腹血糖、空腹胰島素、血脂、甲狀腺功能、肝酶等指標(biāo)的水平。結(jié)果1.單用rhGH治療前、治療6個(gè)月、治療12個(gè)月的HtSDSCA依次升高(p=0.001);但治療前后HtSDSBA的差異大多無(wú)統(tǒng)計(jì)學(xué)意義;治療后12個(gè)月PAH平均升高1.7cm。聯(lián)合用藥組治療前、治療6個(gè)月、治療12個(gè)月的HtSDSCA和HtSDSBA依次升高,且具有統(tǒng)計(jì)學(xué)意義(p=0.022);治療后12個(gè)月PAH平均升高6.4cm。2.單用 rhGH 組 FBG、FINS、HOMA-IR、TC、TG、HDL-C、TG/HDL-C 治療前后的差異均無(wú)統(tǒng)計(jì)學(xué)意義;治療后LDL-C降低(12個(gè)月p=0.043);ALT(6個(gè)月p=0.041)和AST(6個(gè)月p=0.028)有所降低;治療后FT3升高(6個(gè)月p=0.020),FT4先下降,再升高(3個(gè)月p=0.014),治療前后TSH的差異均無(wú)統(tǒng)計(jì)學(xué)意義。聯(lián)合用藥組治療后FBG、FINS、HOMA-IR均升高(12個(gè)月FBG p=0.027;FINS p=0.028;HOMA-IRp=0.028);治療后 TC、TG、LDL-C、HDL-C、TG/HDL-C 與治療前的差異無(wú)統(tǒng)計(jì)學(xué)意義;治療3個(gè)月后,ALT比治療前升高(p=0.042),但尚在正常范圍內(nèi),AST治療前后無(wú)顯著差異;FT3、FT4治療前后的差異無(wú)統(tǒng)計(jì)學(xué)意義,治療后9個(gè)月TSH降低(p=0.028)。3.對(duì)青春發(fā)育情況相似的單用和聯(lián)用患者進(jìn)行組間比較(n=20,單用組11例,聯(lián)用組9例),治療前HtSDSBA、PAH、IGF-1及各代謝指標(biāo)相似。治療后單用組IGF-1高于聯(lián)用組(6個(gè)月p=0.018),GV高于聯(lián)用組(3個(gè)月p=0.011),且GV與GnRHa使用與否顯著相關(guān),治療后HtSDSBA和PAH組間差異無(wú)統(tǒng)計(jì)學(xué)意義;治療后HOMA-IR、TG/HDL、ALT、AST、FT3、FT4、FT3/FT4 及 TSH 組間差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論單用rhGH或聯(lián)合GnRHa治療兒童和青春期矮身材,可提高PAH;青春發(fā)育初期短期治療,兩種方案療效相當(dāng),對(duì)胰島素敏感性、血脂、轉(zhuǎn)氨酶、甲狀腺功能的影響沒(méi)有顯著差異。
[Abstract]:With the development of society and the improvement of national economy, people pay more and more attention to the pursuit of beauty. Height, as an important aspect of beauty, is paid more and more attention. Because of the influence of short stature on patients' self-esteem, life, work and marriage, children and puberty short stature patients and their families often have a strong need to improve their height. The effect of recombinant human growth hormone (rhGH) or gonadotropin releasing hormone analogue (GnRHa) on short stature in children and puberty is still controversial, and the effects of rhGH on glucose metabolism, lipid metabolism and thyroid function are not studied. Little is known about metabolic changes in patients with short stature treated with rhGH and GnRHa. The purpose of this study was to analyze the efficacy of rhGH alone or rhGH combined with GnRHa in children and early puberty patients with short stature and the metabolic changes in the course of treatment. Participants and methods 62 children and puberty patients with short stature were treated with rhGH alone or rhGH combined with GnRHa. Patients before puberty development were treated with rhGH alone; those with obvious youth development were treated with rhGH combined with GnRHa; some patients who had just started youth development were clinically judged to have slower growth rate and greater growth potential. Combined with the wishes of patients and their families, rhGH alone was also used. The levels of height, fasting blood glucose, fasting insulin, blood lipid, thyroid function and liver enzyme were monitored every 3 to 6 months. Result 1. Before and after treatment with rhGH alone, HtSDSCA increased in turn after 6 months and 12 months, but there was no significant difference in HtSDSBA before and after treatment, and the average increase of PAH was 1.7 cm at 12 months after treatment. The HtSDSCA and HtSDSBA of the combined treatment group increased in turn after 6 months of treatment and 12 months of treatment, and were significantly higher than that of the control group, and the PAH increased by 6.4 cm 路2. 2 at 12 months after treatment. In rhGH group, there was no significant difference before and after treatment, LDL-C decreased (12 months, p0.043) and AST (6 months, p0.028) decreased, FT3 increased (6 months, p0.020) and FT4 decreased after treatment, and the difference was not statistically significant before and after treatment, but there was no significant difference before and after treatment, and the level of FT3 increased after 6 months (p 0.020), and decreased at 12 months after treatment (p 0.043) and AST (6 months, p0.041) and AST (6 months, p0.028), and increased after treatment (p 0.020% FT4, P < 0.05). There was no significant difference in TSH before and after treatment. In the combined treatment group, the FBGG FINSMA-IR increased (12 months after treatment, FBG p0. 027 and fins p0. 028, HOMA-IRP 0. 028), and there was no significant difference between the two groups before and after treatment. After 3 months of treatment, the level of alt was higher than that before treatment. However, there was no significant difference in TSH between before and after treatment in normal range. There was no significant difference between before and after treatment. After 9 months of treatment, TSH was decreased by 0.028. 3. A comparison was made between the two groups of patients with similar pubertal development. There were 11 cases in the single use group and 9 cases in the combined group. Before treatment, the levels of HtSDSBAPAHIGF-1 and the metabolic indexes were similar. After the treatment, the IGF-1 of the single group was higher than that of the combined group (6 months p0. 018) GV was higher than that of the combined group (3 months, p0. 011), and there was no significant difference between HtSDSBA and PAH after treatment, but there was no significant difference between the two groups after treatment. Conclusion rhGH alone or combined with GnRHa can improve the height of children and puberty, and the effects on insulin sensitivity, blood lipid, aminotransferase and thyroid function of the two regimens are similar in the early stage of puberty.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R725.8

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