Clinical Analysis Of Idiopathic Hypogonadotropic Hypogonadism

ObjectiveTo retrospectively analyse the clinical characteristics,complications,influencing factors and related pathogenic genes of idiopathic hypogonadotropic hypogonadism(IHH).To improve clinicians' understanding of this disease and provide corresponding guidance for clinical diagnosis and treatment.MethodsClinical data of 23 patients with idiopathic hypogonadotropic hypogonadism admitted to the Department of Endocrinology and Metabolism,General Hospital of Tianjin Medical University from December 2000 to August 2018 were retrospectively analyzed.To compare the clinical characteristics and gonadotropin levels between patients with Kallmann syndrome(KS)and patients with normosmic IHH(nIHH),and to explore the congenital malformation and motor abnormalities of patients with IHH.To explore the related complications of patients with IHH,such as insulin resistance,non-alcoholic fatty liver disease and osteoporosis.Finally,the related pathogenic genes of IHH patients were analyzed.ResultsA total of 23 IHH patients(22 males and 1 females)were included in this study,including 9 males with KS and 14 nIHH patients(13males and 1 females).There was no significant difference in age,height,weight and BMI between KS and nIHH groups.Analysis of IHH patients complicated with congenital malformation and motor abnormalities,among the 9 cases of KS patients,4 patients were complicated with cryptorchidism,1 patient with congenital right kidney deficiency,and 1 patient was complicated with congenital ptosis.Of the 14 patients with nIHH(13 males,1 female),4 had cryptorchidism,one patient was complicated with cleft lip,one patient was concomitant with congenital blindness of the left eye and one patient had congenital cubitus valgus.Spearman rank correlation coefficient was used to analyze the Tanner stages of external genital development of patients,and the stages of external genital development of male patients with IHH were positively correlated with the basic testosterone and LH.For the analysis of IHH related complications,7 male patients(3 KS patients and 4 nIHH patients)in the 23 patients underwent oral glucose tolerance test,and the Homa-IR values of 7 patients were all greater than 1,indicating insulin resistance.Testosterone levels in NAFLD patients were higher than those in nonNAFLD patients,but there was no significant difference in testosterone levels between the two groups.Spearman rank correlation coefficient was used to analyse the correlation between lumbar spine,femoral neck bone density and the basic levels of testosterone and BMI.The results showed that BMD of lumbar spine and femoral neck was positively correlated with BMI.Among the IHH patients,two patients were tested for the related pathogenic genes(1 male patient with KS and 1 female patient with nIHH),respectively KAL1 and FGF8 gene variants.In terms of treatment,among the 22 male patients with IHH,1 patient chose testosterone replacement therapy,17 patients chose HCG intramuscular injection therapy,and 4 patients chose GnRH pump replacement therapy.The female IHH patient was treated with estrogen and progesterone replacement therapy.ConclusionThere was no significant difference in age,height,weight,BMI and gonadotropin levels between KS and nIHH groups.IHH patients may manifest congenital GnRH deficiency alone or have other developmental abnormalities,such as cryptorchidism,cleft lip/palate,congenital blindness,renal deficiency,etc.The higher the basal testosterone and LH,the better the development of external genitalia.IHH patients are prone to IR,NAFLD,osteoporosis and so on.To study the related genes of IHH patients and their families is helpful for the diagnosis and treatment of IHH patients.