脉冲式促性腺激素释放激素疗法可能恢复先天性联合垂体激素缺乏症患者的下丘脑-垂体-睾丸轴功能：一项前瞻性自我对照试验。
Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.
作者信息
Zheng Junjie, Mao Jiangfeng, Xu Hongli, Wang Xi, Huang Bingkun, Liu Zhaoxiang, Cui Mingxuan, Xiong Shuyu, Ma Wanlu, Min Le, Kaiser Ursula B, Nie Min, Wu Xueyan
机构信息
Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, Ministry of Health, Beijing 100730, China.
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
出版信息
J Clin Endocrinol Metab. 2017 Jul 1;102(7):2291-2300. doi: 10.1210/jc.2016-3990.
CONTEXT
The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH.
OBJECTIVE
To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD.
DESIGN
Prospective, self-controlled, 3-month clinical trial.
SETTINGS
University endocrine clinic.
PATIENTS
Men with hypogonadotropic hypogonadism caused by CCPHD.
INTERVENTION
Pulsatile GnRH was administered subcutaneously for 3 months.
MAIN OUTCOME MEASURES
Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis.
RESULTS
A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk.
CONCLUSIONS
This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.
背景
由于先天性联合垂体激素缺乏症（CCPHD）患者数量有限，以及这些患者存在垂体发育不全、促性腺细胞储备不足和对促性腺激素释放激素（GnRH）的促性腺反应受损等情况，尚未对脉冲式GnRH治疗CCPHD患者的有效性进行研究。
目的
评估CCPHD男性患者对脉冲式GnRH治疗的垂体反应。
设计
前瞻性、自身对照、为期3个月的临床试验。
地点
大学内分泌诊所。
患者
由CCPHD导致的低促性腺激素性性腺功能减退男性患者。
干预措施
皮下注射脉冲式GnRH，持续3个月。
主要观察指标
主要终点为血清总睾酮、睾丸体积以及黄体生成素（LH）和卵泡刺激素（FSH）水平。次要终点包括精子发生的情况。
结果
共有40例CCPHD男性患者完成了研究。其中，60%（40例中的24例）对脉冲式GnRH治疗反应良好（反应组）。3个月时，他们的LH和FSH水平升至正常范围，睾酮水平升至8.67±4.83 nmol/L。反应组患者中，33.3%（24例中的8例）实现了精子发生。其余40%（40例中的16例）患者对脉冲式GnRH治疗反应不佳。磁共振成像（MRI）未显示垂体反应与垂体高度和/或垂体柄完整性之间存在任何关联。
结论
本研究表明，即使有MRI证据显示垂体发育不全或发育异常，CCPHD患者的促性腺细胞仍可能存在且具有功能。脉冲式GnRH治疗使60%的CCPHD患者恢复了垂体-睾丸轴功能。这些结果可能直接指导临床治疗选择。
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