[DAX-1基因突变所致先天性肾上腺发育不全患者下丘脑-垂体-睾丸轴功能障碍]

[Dysfunction of hypothalamic-pituitary-testicular axis in patients with adrenal hypoplasia congenita due to DAX-1 gene mutation].

作者信息

Zheng J J, Wu X Y, Nie M, Liu Z X, Wang X, Huang B K, Fu Y, Lu L, Duan L, Mao J F

机构信息

Key Laboratory of Endocrinology, National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2016 Apr 19;96(15):1183-7. doi: 10.3760/cma.j.issn.0376-2491.2016.15.008.

DOI:10.3760/cma.j.issn.0376-2491.2016.15.008

PMID:27117364

Abstract

OBJECTIVE

To evaluate the hypothalamic-pituitary-testicular axis (HPTA) function and spermatogenesis in male patients with X-linked adrenal hypoplasia congenita (AHC) due to DAX-1 gene mutation.

METHODS

Twenty-four adult male patients from Peking Union Medical College Hospital between November 2007 and December 2014 were included.Their DAX-1 gene mutations were confirmed by polymerase chain reaction (PCR) and clinical features, hormone level and semen assay were collected.

RESULTS

All patients presented with adrenal deficiency symptom.21 patients (87.5%) showed the symptoms before the age of 10 years old.The average testicular volume was 2.0 (2.0, 3.8) ml at the baseline in 24 patients.Three patients had cryptorchidism.Serum testosterone level increased from 0.1 (0, 0.5) nmol/L to 13.5 (7.6, 15.4) nmol/L (n=16) after human chorionic gonadotropin (HCG) stimulation.23 out of 24 patients were diagnosed as hypogonadotropic hypogonadism (HH) and only one patient was diagnosed as azoospermia with normal gonadotropin and testosterone level.Combined gonadotropin therapy was administered in seven patients and their serum testosterone level reached 15.3(8.4, 25.3) nmol/L, but no obvious testicular enlargement was observed [(4.0±2.9) vs (4.9±3.3) ml , P=0.270] and seminal analysis revealed persistent azoospermia.Another patient showed response to pulsatile GnRH therapy.Luteinizing hormone(LH) level increased from 1.0 U/L to 9.3 U/L, and follicle stimulating hormone(FSH) level increased from 3.0 U/L to 13.5 U/L.Serum testosterone level increased from 0 nmol/L to 10.0 nmol/L, but testicular volume maintained 3 ml after treatment for two months.

CONCLUSIONS

Male patients with DAX-1 gene mutations presented with primary defect in spermatogenesis and hypogonadotropic hypogonadism.Their Leydig cell function was almost normal, while Sertoli cell and seminiferous tubule function were seriously damaged.

摘要

目的

评估因DAX-1基因突变导致的X连锁先天性肾上腺发育不全（AHC）男性患者的下丘脑-垂体-睾丸轴（HPTA）功能及精子发生情况。

方法

纳入2007年11月至2014年12月期间来自北京协和医院的24例成年男性患者。通过聚合酶链反应（PCR）确认其DAX-1基因突变，并收集其临床特征、激素水平及精液分析结果。

结果

所有患者均有肾上腺功能不全症状。21例患者（87.5%）在10岁前出现症状。24例患者基线时平均睾丸体积为2.0（2.0，3.8）ml。3例患者患有隐睾症。人绒毛膜促性腺激素（HCG）刺激后，16例患者血清睾酮水平从0.1（0，0.5）nmol/L升至13.5（7.6，15.4）nmol/L。24例患者中有23例被诊断为低促性腺激素性腺功能减退（HH），仅1例患者被诊断为无精子症，促性腺激素和睾酮水平正常。7例患者接受了联合促性腺激素治疗，其血清睾酮水平达到15.3（8.4，25.3）nmol/L，但未观察到明显的睾丸增大[（4.0±2.9）ml对（4.9±3.3）ml，P = 0.270]，精液分析显示持续无精子症。另1例患者对脉冲式GnRH治疗有反应。促黄体生成素（LH）水平从1.0 U/L升至9.3 U/L，促卵泡生成素（FSH）水平从3.0 U/L升至13.5 U/L。血清睾酮水平从0 nmol/L升至10.0 nmol/L，但治疗两个月后睾丸体积维持在3 ml。