The Early Predictors Of Serum IGF-1,DHEAS,AMH And BMP-6 In Rapidly Progressive Puberty Girls

Objective:To investigate the early predictors of serum IGF-1,DHEAS,AMH and BMP-6 in rapidly progressive puberty girls.Methods:1、750 girls with breast development in Children’s hospital of Soochow University were recruited from August 2017 to December 2018.The girls were excluded if they showed lost to follow-up,early treatment and did not meet the inclusion criteria after follow-up six months to one year,the remaining 138 girls were divided into CPP(n=32),EP(n=65)and RPP(n=41).Healthy control group is 33 normal physical examination girls,whose age is 8-9 year old.2、All cases were divided into five groups:CPP group,EP-RPP group,EP-SPP group,RPP group and healthy control group,sign informed consent forms,serum,detail medical history,parent’s heights and auxiliary examinations were collected.3、Test the serum concentrations of Insulin-like Growth Factor-1(IGF-1)and Dehydroepiandrosterone sulphate(DHEAS)by Chemical Luminescence,test the serum concentrations of Anti-Mullerian hormone(AMH)and Bone morphogenetic protein(BMP-6)by Enzyme-linked immunosorbent assay.4、The statistical analysis software was SPSS22.0.Results:1、The average height of girls in RPP group was 139.58±4.09cm,the predicting adult height was 152.19±4.63cm according to bone age,the final height for parental height was 158.79±3.64cm,the final height for parental height was significantly higher than the predicting adult height,and the two groups were significant difference(F=0.801,P<0.05),the value of loss height was 6.6±4.19cm.2、The peak value of serum FSH were 15.10(13.86-19.80)mIU/ml,11.99(9.18-16.16)mIU/ml and 11.43(9.37-15.63)mIU/ml respectively in EP-SPP group,EP-RPP group and RPP group.The peak ratio of serum FSH/LH were 3.20(2.44-4.58),1.86(1.05-3.16)and 0.76(0.49-0.99)respectively in EP-SPP group,EP-RPP group and RPP group.The peak value of serum FSH and the peak ratio of serum FSH/LH in EP-SPP group were significant higher than EP-RPP group,the difference between the two groups was statistically significant(P<0.05).There was no significant difference between EP-RPP group and RPP group.3、The value of serum IGF-1 were 166.00(126.50-188.00)ng/ml,199.00(170.50-262.50)ng/ml,252.00(233.00-291.50)ng/ml,288.00(252.00-376.00)ng/ml and 382.00(264.0-499.50)ng/ml respectively in healthy control group,EP-SPP group,EP-RPP group,CPP group and RPP group.The serum IGF-1 in EP-SPP group,EP-RPP group,CPP group and RPP group were all higher than those in healthy control group,the difference was statistically significant(P<0.05).The serum IGF-1 in EP-RPP group was higher than those in EP-SPP group,with the puberty rapidly progressed,the value of serum IGF-1 was gradually increased,which was the highest in the RPP group,the difference between RPP group and EP-RPP was statistically significant(P<0.05).The serum IGF-1 in CPP group was higher than those in EP-RPP group,the difference was statistically significant(P<0.05).The serum IGF-1 in RPP group was higher than those in CPP group,the difference was statistically significant(P<0.05).4、The value of serum DHEAS were 41.65(14.8-59.88)ng/ml,42.50(30.15-79.83)ng/ml,52.32(43.08-98.54)ng/ml,63.30(34.00-81.55)ng/ml and 70.89(51.85-100.02)ng/ml respectively in healthy control group,EP-SPP group,CPP group,EP-RPP group and RPP group,with a gradually increased respectively in healthy control group,EP-RPP group and RPP group,which was the highest in the RPP group,there were significant difference in those group(P<0.05).There were no significant difference between EP-SPP group and healthy control group(P>0.05),and there were no significant difference between CPP group and EP-RPP group(P>0.05)5、The value of serum AMH and BMP-6 in EP-RPP group,EP-SPP group,RPP group,CPP group and healthy control group were no significant difference(P>0.05).6、Receiver operating characteristic(ROC)analysis revealed that the optimal cut-off value of serum IGF-1 to predict rapidly progressive puberty was 232.5ng/ml,for this cut-off value,specificity was 83.30%,sensitivity was 75.00%,the area under the curve was 0.765.The optimal cut-off value of peak value of serum FSH was 13.81mIU/ml,for this cut-off value,specificity was 74.20%,sensitivity was 69.70%,the area under the curve was 0.703.The optimal cut-off value of peak ratio of FSH/LH was 2.33,for this cut-off value,specificity was 77.40%,sensitivity was 63.60%,the area under the curve was 0.732.The area under the ROC curve was 0.795 combined serum FSH with peak ratio of serum FSH/LH.7、There were no significant difference in gestational age,delivery mode,feeding regimens,pregnant disease and short stature of parents between RPP group and SPP group(P>0.05).8、There were no significant difference in gestational age,delivery mode,feeding regimens,pregnant disease and short stature of parents between all puberty patients group and healthy control group(P>0.05).9、The higher value of BA/CA,uterine size,LH,the peak ratio of LH/FSH and IGF-1 and the lower peak ratio of FSH/LH in CPP group compared with EP-RPP group,the difference between the two groups was statistically significant(P<0.05).The higher value of BA/CA,uterine size,LH,the peak ratio of FSH/LH and IGF-1 and the lower peak ratio of FSH/LH in RPP group compared with CPP group,the difference between the two groups was statistically significant(P<0.05).10、Bilateral ovarian volumes in EP-RPP group,EP-SPP group,RPP group and CPP group were no significant difference(P>0.05).Conclusions:1、The peak value of serum FSH and peak ratio of serum FSH/LH in EP-SPP group was higher than those in EP-RPP group,and there was no significant difference of the peak value of serum FSH between EP-RPP and RPP,indicated that the peak value of serum FSH combine with the peak ratio of serum FSH/LH may be used as the one of the early predictors for RPP.2、The value of serum IGF-1 was higher in EP-RPP group than in EP-SPP group,with the puberty rapidly progressed,the value of serum IGF-1 was gradually increased,indicated that IGF-1 was related to the progress of puberty,and may be used as the one of the early predictors for RPP.The optimal cut-off value was 232.5ng/ml,which specificity and sensitivity was 79.00%and 69.00%respectively.Additionally,the value of serum IGF-1 was higher in EP-RPP group,EP-SPP group and CPP group than those in healthy control group,meant that IGF-1 was involved in the initiation of puberty.3、The value of serum DHEAS was higher in all puberty patients group than healthy control group,with the puberty rapidly progressed,the value of serum DHEAS was gradually increased,but there were no significant difference in EP-RPP group,EP-SPP group and CPP group,these findings suggest that although DHEAS cannot be used as an early predictors for RPP,it may be related to Tanner staging4、Bilateral ovarian volumes in EP-RPP group,EP-SPP group,RPP group and CPP group were no significant difference,indicated that ovarian volumes can not be regarded as an parameter to evaluate the stage of puberty.5、The gestational age,delivery mode,feeding regimens,pregnant disease and short stature of parents with a girls were not related to the onset and progression of puberty,further studies are needed on the effects of the mini-puberty and catch-up growth of the progression of puberty.6、Although the higher value of BA/CA,uterine size,LH and IGF-1 in CPP group compared with EP-RPP group,after the puberty rapidly progressed,the RPP group also showed similarly symptoms such as advanced bone age,enlarged uterine and higher hormone levels,which suggested that early menarche and short stage will also happens in early puberty girls,it is important to observe the progression of puberty.