| Objectives:To observe the peripheral blood karyotyping and sex hormone levels in children with hypospadias and to investigate the possible endocrine related etiology.To evaluate if sex hormonal profile of children with hypospadias associates better with comprehensive local anatomical factor score(LAFS) than with urethral meatus location or severity of chordee. To provide the evidence for whether to take hormonal adjuvant therapy according to the local anatomical factor score in relevance to the postoperative prognosis.Materials and methods:122 children with hypospadias aged from 1 month to 149 months(average 20 months of age)were reviewed in Soochow University Affiliated Children’s Hospital from January 2012 to February 2016.All children were not previously treated with androgen stimulation therapy.Peripheral blood karyotype was examined in 93 of 122 children.Pateints were divided into two age groups(≤6month、>6month). The basal level of dehydroepiandrosterone(DHEA), follicle stimulating prime(FSH), luteinizing prime(LH), testosterone(T) and estradiol(E2), procaltin(PRL) was detected and statistically analyzed. DHEA、FSH、T、LH、E2 and PRL were compared between the two groups,to analysis if DHEA and LH associates with T.The location of the hypospadiac meatus and the local anatomic factors of the penis in 61 inpatients were documented to calculate the local anatomical scores.The patients were devided into mild and severe case groups according to meatal location, and then LAFS, FSH, LH and T were compared between the two groups. They were also devided into the first group(≤10°), The second group(> 10°, ≤30°) and the third group(> 30°)according to the degree of chordee, and then LAFS and T compared.FSH、LH、E2、PRL、DHEAand T were compared between the two groups(group I≤19, II > 19)according to the LAFS in 61 inpatients.41 children over 6 months of age received gonadal hormone releasing hormone(GnRH) stimulation test, and the basal level of serum follicle stimulating hormone(FSH) and luteinizing hormone(LH), and their successive concentrations in 30 min, 60 min, 90 min and 120 min after injection of GnRH were documented comparing the peak value and amplitude.Human chorionic gonadotropin(HCG) stimulation test was done in 17 children over 6 months of age, and the basal level of serum testosterone(T) and their successive changes were recorded in 30 min, 60 min, and 72 h after the injection of HCG.The concentration of serum dihydrotestosterone(DHT) of 29 patients and the testosterone / dihydrotestosterone(T/DHT) ratio were documented in 29 patients and analyzed together with the other clinical data.The sex hormone levels were compared in association with different age, meatal location, chordee and LAFS with SPSS19.0 statistical software analysis.The data were expressed as mean±standard deviation(?x?s) or percentage.Testof homogeneity of variance were done before analysis of the data, means were compared with independent samples t test or with single factor variance analysis(ANOVA)taking p < 0.05 as the level of statistically significance.Results:Chromosome karyotype was 46, XY in 90 cases of 93 hypospadiac patients tested, 3 cases of abnormal karyotype were detected with 46 XY, del(11)(q23), 46 XY, t(7; 14) /46 XY and 46 XY, inv(9)(p11q12) respectively, and 2 of them were isolated proximal hypospadias with chromosome aberration rate was 3.2%.In 61 cases of hospitalized children, there were 31 isolated hypospadias and 30 cases were associated with other malformations(with 49.2% deformity rate). 14 cases were associated with penile scrotal transposition, 8 cases with cryptorchidism, 3 cases with indirect inguinal hernia or hydrocele, 2 cases with prostatic utricle, and 3 cases with other malformations. 14 cases were associated with penile scrotal transposition were all severe hypospadias.Penile scrotal transposition is the most commonly seen in severe hypospadias, followed by cryptorchidism, hernia and hydrocele.Among age groups, there were 58 cases below 6 months of age(including 6 months) and 64 cases over 6 months of age. The DHEA, FSH, LH, T, E2, PRL in patients over 6 months of age were lower than the patients below the age of 6 months, with DHEA, LH, T and PRL values statistically significant difference between the two groups(p < 0.05).There were 17 mild cases and 24 severe cases in a total of 41 cases of hypospadias undergoing GnRH stimulation test. All of them were positively reacted. LH peaked at 120 min in 24 cases, at 90 min in 7 cases, at 60 min in 3 cases, and at 30 min in 7cases. FSH peaked at 120 min in 36 cases, at 90 min in 2 cases, at 60 min in 3 cases. Most of the serum FSH and LH peak concentrations sustained to 120 min in two groups. FSH were increased slightly more in severe hypospadias than thatin mild cases, howeverthe differentce was not statistically significant(p> 0.05), and LH incrementwas not stastistically different between mild and severe hypospadias. The peak levels of FSH and LH were not significantly different between mild and severe hypospadias groups, and their rising amplitudes were also not significantly different between the two groups(p> 0.05).Of 17 HCG stimulation test cases, 7 were adjudged to have positive reaction, 5 have no positive reaction and 5 have no reaction but falling. The basal level of testosterone were higher in mild hypospadias than that in severe hypospadias, the difference had statistically significant.The testosterone profile at72 h were significantly high in 17 cases. The serum dihydrotestosterone(DHT) patients were documented in 29 patients, and 22 of them(75.9%)were normal, 2 cases over normal range and 5 cases below normal range. The testosterone profilewas two times more higher than normal in about half(12 out of 29 cases), and the remaining was below the normal level. The testosterone / dihydrotestosterone(T/DHT) ratio were documented in the normal level with a mean value of 0.5(max 2.51 and min 0.03) in 29 patients, and there was no statistical difference between mild and severe hypospadias.Of 61 subjects of hospitalized children,there were 18 mild cases in group A, 43 severe cases in group B. 30 cases belonged to group I and 31 cases belonged to group II based on LAFS.There were17 cases in first group,28 cases in second groups and16 cases in third group based on the severity of chordee.The LAFS score was higher in Group A than in Group B. LAFS of most severe hypospadias(93%, 40 cases) were below 19, and 6 cases(33%) in group A had lower LAFS. Group B had a higher FSH in comparison to Group A but the difference was not statistically significant. When mean values of hormones were evaluated with respect to the severity of chordee, it was observed that more severe chordee was associated with lower T levels,though this difference was not stastistically significant. FSH, LH was higher, and E2, T lower in the first group than in the second groupamong LAFs groups.Conclusion:1. Severe hypospadias especially associated with other malformations are more likely to have the possibility of chromosomal aberration and necessitate for chromosomal karyotype examination.2. The children with hypospadias under the age of six months appeared a sexual hormone secretion peak, and then gradually decreased with age before puberty indicating minipuberty are present in the majority of children with hypospadias.3.The hypothalamic pituitary gonadal axis(HPG axis) is intact in most children with hypospadias with a delay phenomenon in someand enhanced in others, Weak testicular Leydig cell function but normal functional reservation is observed in some children with severe hypospadias.4.Lower androgenic output was noted in children with severe chordee and low LAFS.Sertolicell dysfunction was documented in children with severe hypospadias and low LAFS. LAFS should be considered a better marker for deciding onhormonal adjuvant therapy. |
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