上海交通大学学报(医学版)

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短期GnRH脉冲治疗对先天性低促性腺激素性性腺功能减退症青少年期男性患者垂体⁃睾丸功能的作用

王斐, 龚艳, 许丽雅, 刘庆旭, 李妍, 郭盛, 李嫔()   

  1. 上海市儿童医院,上海交通大学医学院附属儿童医院内分泌科,上海 200062
  • 收稿日期:2022-07-18 接受日期:2022-11-09 出版日期:2022-12-20 发布日期:2022-12-20
  • 通讯作者: 李嫔 E-mail:lipin21@126.com
  • 作者简介:王 斐(1983—),女,副主任医师,硕士;电子信箱:w-fly0620 @163.com。
  • 基金资助:
    上海市“科技创新行动计划”医学创新研究专项重点项目(21Y21901000);上海市“促进市级医院临床技能与临床创新能力三年行动计划”疑难疾病精准诊治攻关项目(SHDC2020CR2058B)

Effect of short-term GnRH pulse therapy on pituitary-testicular function in adolescent male patients with congenital hypogonadotropic hypogonadism

WANG Fei, GONG Yan, XU Liya, LIU Qingxu, LI Yan, GUO Sheng, LI Pin()   

  1. Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China
  • Received:2022-07-18 Accepted:2022-11-09 Online:2022-12-20 Published:2022-12-20
  • Contact: LI Pin E-mail:lipin21@126.com
  • Supported by:
    Medical Innovation Research Special Project in "Science and Technology Innovation Action Plan" of Shanghai(21Y21901000);Precise Diagnosis and Treatment Project for Difficult Diseases in "Three-year Action Plan for Promoting Clinical Skills and Innovation Capacity of Municipal Hospitals" of Shanghai(SHDC2020CR2058B)

摘要:

目的·探讨短期促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)脉冲治疗对先天性低促性腺激素性性腺功能减退症(congenital hypogonadotropic hypogonadism,CHH)青少年期男性患者垂体及睾丸功能的作用。方法·回顾性研究2016年1月—2021年6月接受GnRH脉冲治疗的CHH青少年期男性患者20例,收集患者临床资料。治疗方法为皮下持续脉冲泵给予戈那瑞林治疗1周(20例),其中5例患者持续治疗3个月;剂量为每个脉冲8~10 μg,脉冲间隔90 min。于GnRH脉冲治疗前及治疗1周、1个月和3个月时,检测促黄体生成素(luteinizing hormone,LH)、促卵泡刺激素(follicle-stimulating hormone,FSH)、睾酮水平;治疗3个月时测量睾丸体积变化。20例CHH患者均进行了全外显子基因测序。结果·20例CHH患者就诊年龄为14.35(14.08,15.31)岁,临床均表现为幼稚型睾丸、小阴茎,其他还伴有肥胖(12/20)、嗅觉障碍(9/20)、胰岛素抵抗(4/20)、隐睾(4/20)、身材矮小(3/20)等。患者身高为161.79(154.90,173.25)cm,体质量指数为23.80(20.51,27.46)kg/m2,睾丸体积为0.91(0.55,1.25)mL。抑制素B为39.67(11.29,64.97)pg/mL,LH基础值为0.20(0.10,0.30)IU/L,FSH基础值为0.87(0.23,0.89)IU/L,睾酮基础值为0.92(0.38,1.49)nmol/L。持续GnRH脉冲治疗1周后,20例患者LH、FSH的基值和峰值以及睾酮峰值均显著升高(均P<0.05)。其中接受3个月治疗的5例患者治疗1周、1个月、3个月时,LH、FSH的基值和峰值均呈逐渐升高趋势;治疗3个月时LH、FSH基值和峰值,以及睾酮峰值均比治疗前显著增高(均P<0.05),睾丸体积也显著增大(P=0.004)。20例患者中仅14例检测到基因突变,分别为人成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)突变7例、anosmin 1蛋白基因(anosmin 1,ANOS1)突变4例、前动力蛋白2受体(prokineticin receptor 2,PROKR2)突变2例、前动力蛋白2(prokineticin 2,PROK2)突变1例。GnRH脉冲治疗1周对FGFR1突变和ANOS1突变患者垂体-睾丸功能的影响差异无统计学意义。结论·青少年期男性CHH患者接受持续GnRH脉冲治疗1周后垂体-睾丸功能出现应答,治疗3个月有助于该类患者青春期第二性征的诱导。

网络首发地址:https://kns.cnki.net/kcms/detail//31.2045.R.20221216.1451.001.html

网络首发时间:2022-12-20 10:16:33

关键词: 低促性腺激素性性腺功能减退症, 促性腺激素释放激素, 脉冲治疗, 青少年期

Abstract:

Objective ·To investigate the effect of short-term gonadotropin-releasing hormone (GnRH) pulse therapy on pituitary and testicular function in the adolescent male patients with congenital hypogonadotropic hypogonadism (CHH). Methods ·A retrospective study was conducted on 20 adolescent male patients with CHH who received GnRH pulse therapy from January 2016 to June 2021, and their clinical data were collected. They were treated with subcutaneous continuous pulsed administration of gonadorelin by the pump for 1 week (20 cases), of which 5 cases were treated for 3 months. The dose was 8?10 μg per pulse, and the pulse interval was 90 min. The levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were measured before GnRH pulse therapy at 1 week, 1 month and 3 months after treatment. After 3 months of treatment, the testicular volume was measured. All 20 patients with CHH underwent whole exome sequencing. Results ·The age of 20 CHH patients was 14.35 (14.08, 15.31) years old. The clinical manifestations were infantile testis (20/20) and micropenis (20/20), followed by obesity (12/20), dysosmia (9/20), insulin resistance (4/20), cryptorchidism (4/20), and short stature (3/20). The patients' height was 161.79 (154.90, 173.25) cm, body mass index was 23.80 (20.51, 27.46) kg/m2, and testicular volume was 0.91 (0.55, 1.25) mL. Inhibin B was 39.67 (11.29, 64.97) pg/mL; the base values of LH, FSH and testosterone before therapy were 0.20 (0.10, 0.30) IU/L, 0.87 (0.23, 0.89) IU/L, and 0.92 (0.38, 1.49) nmol/L, respectively. After 1 week of continuous GnRH pulse therapy, the base and peak values of LH and FSH and the peak value of testosterone in the 20 patients significantly increased (all P<0.05). In the 5 patients treated for 3 months, the base values and peak values of LH and FSH gradually increased with the prolongation of treatment time. After 3 months of treatment, the base values and peak values of LH and FSH, and the peak value of testosterone were significantly higher than those before treatment (all P<0.05), and the testicular volume was also significantly increased (P=0.004). Gene mutations were detected in only 14 of 20 patients, including fibroblast growth factor receptor 1 (FGFR1) mutations in 7 cases, anosmin 1 (ANOS1) mutations in 4 cases, prokineticin receptor 2 (PROKR2) mutations in 2 cases, and a prokineticin 2 (PROK2) mutation in 1 case. There was no significant difference of the effect of GnRH pulse therapy for 1 week on pituitary-testicular function between the patients with FGFR1 mutations and ANOS1 mutations. Conclusion ·The continuous GnRH pulse therapy for 1 week can make pituitary-testicular function respond in adolescent male CHH patients; the treatment for 3 months helps to induce the secondary sexual characteristics of puberty.

Key words: hypogonadotropic hypogonadism, gonadotropin-releasing hormone (GnRH), pulse therapy, adolescent

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