[Dysfunction of hypothalamic-pituitary-testicular axis in patients with adrenal hypoplasia congenita due to DAX-1 gene mutation].
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.
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.
J J
JJ
Zheng
X Y
XY
Wu
M
M
Nie
Z X
ZX
Liu
X
X
Wang
B K
BK
Huang
Y
Y
Fu
L
L
Lu
L
L
Duan
J F
JF
Mao
D000309:Adrenal Insufficiency / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D005640:Follicle Stimulating Hormone / Q000097:blood; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D000075262:Hypoadrenocorticism, Familial; D007006:Hypogonadism / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009154:Mutation; D013091:Spermatogenesis; D013737:Testis / Q000503:physiopathology*
D006063:Chorionic Gonadotropin; D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone