促性腺激素改善多种垂体激素缺乏患儿第二性征及性激素水平的时效性

发布时间：2018-06-04 04:38

本文选题：多种垂体激素缺乏症 + 促性腺激素　；参考：《山东大学》2013年硕士论文

【摘要】：1.研究背景及目的多种垂体激素缺乏症(MPHD)是一类以生长激素(GH)缺乏伴一种或多种其他垂体激素缺乏为特征的疾病,其最常见的伴发缺乏激素是促性腺激素,但临床对于性腺功能低下的治疗无统一标准和指南。目前常用方法是青春期时给予性激素替代治疗改善第二性征,在有生育需求时给予促性腺激素类似物如人绒毛膜促性腺激素(hCG)和人绝经期促性腺激素(hMG)治疗。但性激素对生育无改善,甚至会损害生育能力和终身高。本研究的目的为观察早期,即青春期即给予促性腺激素替代治疗对MPHD患儿性腺发育的影响。 2.对象与方法对象 2007.2---2013.2山东大学附属省立医院儿科内分泌门诊收治的多种垂体激素缺乏症患儿,其中伴有促性腺激素低下、男性年龄大于12岁、女性年龄大于11岁者作为研究对象。按开始治疗年龄分为2组：①青春期组：男性年龄大于等于12岁且小于16岁,女性年龄大于等于11岁且小于14岁,共29例,男性26例,女性3例；②青春期后组：男性年龄大于等于16岁,女性年龄大于等于14岁,共31例,男性26例,女性5例。方法所有男性患儿均给予hCG及hMG肌注,所有女性患儿给予hMG肌注,每3天1次,每次hCG1000u～2000u、hMG75u,3个月为1疗程。同时其他缺乏激素给予替代疗法,使患儿相应激素水平和临床表现维持正常。每3个月复查,至少随访6个月,其中43例观察足9个月,8例观察到36个月。观察指标分别记录用药前和用药后3个月、6个月时的血清性激素水平(促卵泡生成素FSH、黄体生成素LH、雌二醇E2、睾酮To)、体格检查(身高H、乳房和阴毛发育Tanner分期、阴茎长度和周长、睾丸体积)、影像学检查(子宫、卵巢和睾丸B型超声,骨龄BA,下丘脑-垂体核磁共振成像扫描H-P MRI)和其他相关检查结果(如精液分析)。 3.结果 (1)青春期组用药前FSH0.52±0.53mIU/ml, LH0.14±0.27mIU/ml, E23.8±8.2pg/ml, To0.09±0.21ng/ml,用药3个月FSH、E2、To较用药前显著升高(p分别0.01、0.001、0.01),用药6个月FSH、LH、E2、To均显著高于用药前,FSH3.49±3.57mIU/ml(P0.01), LH2.11±3.2mIU/ml (P0.01), E221.77±13.44pg/ml (P0.001), To3.97±2.71ng/ml(P0.001)。用药3个月FSH、LH、E2和To增高值与用药6个月比较无显著性差异(P均0.05)。用药前Tanner分期均为Ⅰ期,用药6个月有5人进入Ⅱ期,1人Ⅲ期。男性阴茎长度和周长均明显增长(P0.001),睾丸容积由1.18±0.91m1增大至5.64±2.38ml(P0.001),有效率96.2%。女性B超显示子宫体积增大、卵巢内出现卵泡。 (2)青春期后组用药前FSH0.95±0.82mIU/ml, LH0.21±0.37mIU/ml, E29.85±12.07pg/ml, To0.89±1.83ng/ml,用药3个月E2、To明显升高(p分别0.001、0.01),用药6个月FSH、E2和To显著高于用药前,FSH2.11±1.85mIU/ml (P0.01), LH0.25±0.56mIU/ml (P0.5), E228.17±23.06pg/ml (P0.01), To3.28±3.38ng/ml (P0.01).用药6个月LH、E2和To增高值与3个月比较无显著性差异(P均0.5),FSH增高明显(P0.05)。用药前Tanner分期有22人Ⅰ期,9人Ⅱ期,用药后Ⅱ期有13人,Ⅲ期7人。男性阴茎长度和周长均明显增长(P0.001),睾丸容积从2.40±1.75m1增大到4.73±2.16ml(P0.001),有效率76.9%。。用药6个月后有2例女性月经初潮,男性中有9例出现遗精,1例已结婚育有一子。 (3)两组比较：青春期组FSH和LH在用药后3个月和6个月的增长值均明显高于青春期后组(P均0.05)。E2和To增长值两组间无显著性差异(P0.1)。两组间阴茎长度和周长增长值无明显差异,青春期组睾丸体积较青春期后组增大明显(P0.01)。 (4)不同垂体激素缺乏患者在两组分布无差异(P0.1),其他激素水平维持正常时,缺乏不同垂体激素的MPHD患儿应用促性腺激素治疗后激素水平升高和第二性征改变无明显差异(P0.05)。 (5)青春期组治疗前后身高、骨龄小于青春期后组,但预期成人身高(PAH)始终高于青春期后组(P0.05)。用药后两组骨龄变化无明显差异(P0.1),但青春期组身高增长值更大(P0.01)。 (6)有无垂体柄阻断综合征患者的初始激素水平、第二性征和疗效比较无显著性差异(P0.05)。 (7)LH、睾丸容积变化值与开始治疗年龄呈负相关(R分别0.3、0.4,P分别0.05、0.01)。 4.结论 (1)青春期和青春期后开始促性腺激素替代治疗均可改善患儿第二性征和性激素水平,而青春期开始治疗对患儿性腺功能的恢复更有利,且开始治疗时间越晚,疗效越差。 (2)青春期开始治疗者对预期成人身高无损害,有利于终身高。 (3)其他激素水平维持正常时,缺乏不同垂体激素的MPHD患儿应用促性腺激素替代疗法后性激素水平和第二性征发育变化无明显差异。
[Abstract]:1. background and purpose of research
Multiple pituitary hormone deficiency (MPHD) is a class of diseases characterized by the lack of growth hormone (GH) with one or more other pituitary hormones. The most common associated deficiency of hormone is gonadotropin. However, there is no unified standard for the treatment of hypogonadism and the south. The common method is to give sex hormone replacement at puberty. Treatment improves secondary sex, and gives gonadotropin analogues such as human chorionic gonadotropin (hCG) and human menopause gonadotropin (hMG) at birth demand. However, sex hormone does not improve fertility and even damages fertility and final height. The aim of this study was to give gonadotropin in the early stages of adolescence. The effect of alternative therapy on the gonadal development of children with MPHD.
2. objects and methods
object
2007.2---2013.2 a variety of children with pituitary hormone deficiency treated in the Department of pediatric endocrinology, affiliated Provincial Hospital of Shandong University, with low gonadotropin, male age more than 12 years old and women older than 11 years of age as research subjects. The age of the beginning of treatment is divided into 2 groups: (1) the adolescent group: the male age is more than 12 years old and small. At the age of 16, women are more than 11 years old and less than 14 years old. There are 29 cases, 26 men and 3 women. 2. After puberty, male age is more than or equal to 16 years, female age is more than or equal to 14 years. There are 31 cases, 26 men and 5 women.
Method
All male children were given hCG and hMG intramuscular injection. All female children were given hMG intramuscular injection, 1 times every 3 days, each hCG1000u to 2000u, hMG75u, 3 months for 1 courses. At the same time, the other lack of hormone replacement therapy made the corresponding hormone level and clinical manifestation normal. Every 3 months reexamination, at least for 6 months, 43 cases were observed for 9 months. 8 cases were observed for 36 months.
Observation index
Serum sex hormone levels (follicle generating hormone FSH, luteinizing hormone LH, estradiol E2, testosterone To), physical examination (H, Tanner staging of breast and pubic hair, penis length and perimeter, testicular volume), and imaging examination (uterus, ovarian and testicular B ultrasound, bone age BA, hypothalamus - hypothalamus -) were recorded respectively at 3 months and 6 months after medication, respectively. Pituitary magnetic resonance imaging scanning H-P MRI) and other related examination results (such as semen analysis).
3. results
(1) the puberty group was FSH0.52 + 0.53mIU/ml, LH0.14 + 0.27mIU/ml, E23.8 + 8.2pg/ml, To0.09 + 0.21ng/ml, the medication was 3 months FSH, E2, To was significantly higher than before the medication (P respectively). .001), To3.97 + 2.71ng/ml (P0.001). There was no significant difference in the value of FSH, LH, E2 and To for 3 months (P 0.05). The Tanner staging of the drugs before medication was stage I, and 5 people entered stage II and 1 in 6 months. The male penis length and Zhou Changjun increased significantly (P0.001), and the volume of the testis increased from 1.18 + 0.91m1 to 5.64. 0.001) the effective rate was 96.2%. B ultrasound showed that the volume of uterus increased and ovarian follicles appeared.
(2) after adolescence, FSH0.95 + 0.82mIU/ml, LH0.21 + 0.37mIU/ml, E29.85 + 12.07pg/ml, To0.89 + 1.83ng/ml, 3 months E2, To significantly increased (P 0.001,0.01), 6 months of medication. Ng/ml (P0.01). There was no significant difference in the 6 month LH, E2 and To increased value compared with 3 months (P 0.5), FSH increased significantly (P0.05). Before medication, there were 22 people in stage I stage and 9 stage II stage, 13 in stage II and 7 in stage II. The male penis length and Zhou Changjun increased significantly (P0.001), and the volume of testis increased from 2.40 + 1.75m1 to 4.73 + 2.16ml. 01) the effective rate of 76.9%.. Was 2 months after menarche in 6 months, 9 of male cases had seminal emission, and 1 had married one child.
(3) the comparison between the two groups: the growth values of FSH and LH in the puberty group were significantly higher than those of the post puberty group (P 0.05) and the growth values of.E2 and To (P0.1). There was no significant difference in the penis length and perimeter growth between the two groups, and the volume of testosterone in puberty group was significantly higher than that in the post puberty group (P0.01).
(4) there was no difference in the distribution of the two groups in the patients with different pituitary hormone deficiency (P0.1), and when the other hormone levels were normal, there was no significant difference in the level of hormone level and the secondary sex change after the gonadotropin treatment (P0.05) in children with the lack of different pituitary hormones.
(5) the height of the puberty group was less than that of the post puberty group before and after the treatment, but the expected adult height (PAH) was always higher than that in the post puberty group (P0.05). There was no significant difference in bone age between the two groups after the treatment (P0.1), but the height growth of the puberty group was higher (P0.01).
(6) there was no significant difference in the initial hormone levels between patients with and without pituitary stalk interruption syndrome (P0.05).
(7) LH, the volume of testicular volume was negatively correlated with the age of onset (R 0.3,0.4, P 0.05,0.01, respectively).
4. conclusion
(1) gonadotropin replacement therapy at puberty and puberty can improve the secondary sex and sex hormone levels in children, and the onset of puberty is more favorable for the recovery of the sexual gland function of the children, and the later the treatment time is, the worse the curative effect is.
(2) the onset of puberty is not harmful to the expected adult height, and is beneficial to the final height.
(3) when other hormone levels are normal, there is no significant difference in the level of sex hormone and the development of secondary sex sex hormone levels in children with MPHD lacking different pituitary hormones.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R725.8

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