本文選題：特發(fā)性低促性腺激素性性腺功能減退癥 + 致病基因��； 參考：《第三軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：研究背景:特發(fā)性低促性腺激素性性腺功能減退癥(idiopathic hypogonadotrpic hypogonadism,IHH)是指因先天性下丘腦促性腺激素釋放激素(Gn RH)神經(jīng)元功能受損,GnRH合成、分泌或作用障礙,導(dǎo)致垂體分泌促性腺激素減少,進(jìn)而引起性腺功能不足的一類(lèi)疾病。IHH發(fā)病率男性為1/1萬(wàn),女性為1/5萬(wàn)。隨著人們對(duì)于其病因?qū)W認(rèn)識(shí)的不斷發(fā)展和進(jìn)步,目前IHH已被證實(shí)是一類(lèi)基因遺傳性疾病,同時(shí)越來(lái)越多的IHH相關(guān)性基因被發(fā)現(xiàn)。男性IHH患者常因生理上缺陷而心理自卑,嚴(yán)重影響正常社交與正常婚戀,造成家庭、社會(huì)負(fù)擔(dān)。針對(duì)男性IHH患者存在第二性征發(fā)育異常,青春期性成熟推遲/終止,生精功能障礙等問(wèn)題,傳統(tǒng)的促性腺激素治療方法,需要長(zhǎng)期規(guī)律性進(jìn)行肌肉注射治療,存在治療繁瑣,療程長(zhǎng),患者難以堅(jiān)持等缺點(diǎn)。近年來(lái)新出現(xiàn)的Gn RH微量泵自動(dòng)脈沖式輸注治療的方法,為IHH患者提供了更加理想的治療措施。Gn RH脈沖泵模擬人體Gn RH生理脈沖,更加符合機(jī)體自身下丘腦-垂體-性腺調(diào)節(jié)軸的生理性調(diào)節(jié)機(jī)制,但其臨床應(yīng)用經(jīng)驗(yàn)尚少,長(zhǎng)期治療對(duì)男性外生殖器發(fā)育的改善,對(duì)男性生殖能力和性功能恢復(fù)的影響等尚缺乏系統(tǒng)深入研究。研究目的:評(píng)價(jià)Gn RH微量泵脈沖治療成年男性IHH患者的中遠(yuǎn)期療效與安全性;通過(guò)對(duì)IHH患者遺傳因素的篩查,探討患者遺傳因素與Gn RH脈沖泵治療有效性之間的相關(guān)性,從而尋求成年男性IHH的最佳治療策略。研究方法:選擇從2013年8月至2016年12月就診于我院,符合IHH診斷標(biāo)準(zhǔn),GnRH興奮試驗(yàn)確定垂體,性腺反應(yīng)性良好的成年男性患者共30例,采用前瞻性自身對(duì)照研究方法,首先記錄患者治療前臨床特征、性激素檢查結(jié)果,然后采用GnRH微量泵進(jìn)行治療,于治療期間不同時(shí)間段,如3,6,12個(gè)月分別對(duì)患者進(jìn)行嚴(yán)格隨訪觀察并詳細(xì)記錄患者治療期間的一般性特征變化、性激素及促性腺激素變化、外生殖器形態(tài)大小變化、精液數(shù)質(zhì)量變化,統(tǒng)計(jì)分析IHH患者采用GnRH泵治療的中遠(yuǎn)期療效,同時(shí)了解患者在GnRH泵治療期間所出現(xiàn)的不良事件。對(duì)IHH患者進(jìn)行相關(guān)致病基因篩查,并結(jié)合臨床,分析致病基因與臨床療效的相關(guān)性。研究結(jié)果:本研究納入30位患者,平均隨訪時(shí)間15.9(2-40)個(gè)月,治療1年以上20例,半年~1年3例,3月~半年4例,3月以下3例�；颊咧委熐安G丸體積(3.43±1.94)ml,黃體生成素(LH)(0.66±0.60)IU/L,卵泡刺激素(FSH)(1.25±0.85)IU/L,睪酮(T)(0.50±0.51)ng/ml,陰莖牽長(zhǎng)(5.77±1.47)cm,陰莖靜息長(zhǎng)度(3.68±1.06)cm,陰莖周徑(5.16±1.31)cm;帶泵治療半年患者睪丸體積(6.55±2.13)ml,LH(6.60±5.10)IU/L,FSH(5.36±3.10)IU/L,T(2.32±1.31)ng/ml,陰莖牽長(zhǎng)(7.93±1.22)cm,陰莖靜息長(zhǎng)度(4.91±0.81)cm,陰莖周徑(7.21±1.29)cm,均較治療前有顯著提高(p0.01)。帶泵治療1年以上患者睪丸體積(8.93±2.40)ml,LH(6.20±3.86)IU/L,FSH(4.93±2.38)IU/L,T(3.59±1.03)ng/ml,陰莖牽長(zhǎng)(9.29±1.45)cm,陰莖靜息長(zhǎng)度(5.82±0.77)cm,陰莖周徑(8.13±0.97)cm,均較治療前有顯著提高(p0.01),外生殖器大小、T水平較半年前有進(jìn)一步顯著改善提高(p0.05)。治療前30例患者無(wú)手淫,無(wú)遺精,僅有2例患者有遺精(精液中無(wú)精子),治療半年以上23例患者均相繼出現(xiàn)遺精并伴經(jīng)常性勃起,其中20例患者取得精液,16例出現(xiàn)精子,2例已婚患者配偶自然妊娠。所有患者治療期間未見(jiàn)明顯不良反應(yīng),患者依從性良好。14例患者自愿行基因檢測(cè),2例患者發(fā)現(xiàn)明確致病基因,2例發(fā)現(xiàn)錯(cuò)義突變和1例發(fā)現(xiàn)同義突變(臨床意義不明)。由于本研究所發(fā)現(xiàn)存在致病基因例數(shù)較少,暫無(wú)法得出存在致病基因與否和臨床療效好壞之間的明確相關(guān)性。研究結(jié)論:GnRH脈沖泵治療成年男性IHH,中遠(yuǎn)期療效理想,安全性良好,是IHH患者的首選治療方案。
[Abstract]:Background: idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotrpic hypogonadism, IHH) refers to the impairment of the function of Gn RH neurons in the congenital hypothalamus (Gn RH), the synthesis, secretion, or dysfunction of GnRH, which leads to the secretion of gonadotropin in the pituitary and then the insufficiency of the gonadotropin. The incidence of.IHH in a class of diseases is 1/1 million and 1/5 million for women. With the continuous development and progress of people's knowledge of etiology, IHH has been proved to be a genetic hereditary disease, and more and more IHH related genes are found. Male IHH patients often suffer from psychological inferiority because of physiological defects, which seriously affect normal social and social conditions. Normal marriage and love cause family and social burden. For male IHH patients, there are problems of abnormal development of secondary sex syndrome, delayed sexual maturity, termination of puberty, and spermatogenic dysfunction. The traditional method of gonadotropin therapy requires long-term regularity of intramuscular injection therapy, which has some shortcomings in recent years, such as tedious treatment, long treatment process, and hard to insist on patients. The new method of Gn RH micro pump automatic pulse infusion therapy provides a more ideal treatment for IHH patients with.Gn RH pulse pump to simulate human Gn RH physiological pulse, which is more in line with the physiological regulation mechanism of the hypothalamus pituitary gonad axis adjustment axis of the body itself, but the experience of its application to the bed is few, and the long-term treatment for male exogeny Lack of systematic and in-depth study on the effects of colonization development on male reproductive capacity and sexual function recovery. Objective: To evaluate the long-term efficacy and safety of Gn RH micropump pulse therapy in the treatment of adult male IHH patients; to explore the genetic factors of patients with IHH and the efficacy of Gn RH pulse pump in the treatment of patients. To seek the best treatment strategy of adult male IHH. Study methods: select from August 2013 to December 2016 in our hospital, conform to the IHH diagnostic criteria, GnRH excitation test to determine the pituitary, 30 adult male patients with good gonadal reactivity, using a prospective self-control study, first record the patients before treatment. The clinical features, the results of the sex hormone examination, and then the GnRH micropump. During the treatment, the patients were followed up and observed at different time periods, such as 3,6,12 months, and recorded the general characteristics of the patients during the treatment, the changes of sex hormone and gonadotropin, the change of the shape and size of the genitals, the quality of the semen. The IHH patients were treated with the GnRH pump for the middle and remote effect, and the adverse events occurred during the GnRH pump treatment. The related genes were screened for the IHH patients and the correlation between the pathogenetic genes and the clinical efficacy was analyzed. The results were included in the study. The study included 30 patients with an average follow-up time of 15.9 (2-4 0 months, 20 cases for more than 1 years, 3 six months ~1 year, 4 cases in March to six months and 3 cases below March. The volume of testis before treatment (3.43 +. 1.94), LH (0.66 + 0.60) IU/L, follicle stimulating hormone (1.25 + 0.85), T (0.50 +) ng/ml, penile stretch (3) cm, penile resting length (3) cm, penis circumference diameter 1.31) cm (6.55 + 2.13), LH (6.60 + 5.10) IU/L, FSH (5.36 + 3.10) IU/L, T (2.32 + 1.31) ng/ml, penile stretch (7.93 + 1.22) cm, penis resting length (4.91 + 0.81) cm and penile circumference cm, both were significantly higher than before treatment (P0.01). (6.20 + 3.86) IU/L, FSH (4.93 + 2.38) IU/L, T (3.59 + 1.03) ng/ml, penile stretch (9.29 + 1.45) cm, penis resting length (5.82 + 0.77) cm, and penis circumference (8.13 + 0.97) cm, which were significantly higher than before treatment (P0.01), the size of the external genitals, T levels were further improved (P0.05) than before half a year. No masturbation, no remains before treatment before treatment. Only 2 patients had spermatospermia (spermatospermia in semen), 23 of them had spermatozoa and frequent erectile, of which 20 had semen, 16 had spermatozoa and 2 married couples had natural pregnancies. All patients had no obvious adverse reactions during the treatment. Patients with good compliance,.14 patients voluntarily performed genes. 2 patients found clear pathogenic genes, 2 cases found missense mutation and 1 cases of synonymous mutation (clinical significance). Because the number of pathogenic genes found in this study was less, there was no clear correlation between the existence of pathogenic genes and the clinical efficacy. Conclusion: GnRH pulse pump was used to treat adult male IHH, Medium and long term curative effect is ideal and safe. It is the first choice for IHH patients.

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R588

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