Effects And Influence On Related Indexes Of Replacement Therapy With Recombinant Human Growth Hormone On The Treatment Of Short Stature Children

Objective:1.To observe the therapeutic effect of domestic recombinant human growth hormone（recombinant human growth hormone,rhGH）replacement therapy on the growth hormone deficiency（GHD）and idiopathic short stature（ISS）in children.2.The changes of serum indexes such as insulin-like growth factor-1（inulin-like growth factor,IGF-1）,thyroid hormone（thyrooid hormone,TH）,fasting blood glucose（fatblood glucose,FBG）,serum uric acid and growth plate-related bone formation indexes such as bone-specific alkaline phosphatase（bone specific alkaline phosphatase,BAP）,bone calcium protein（osteocalin,OC）,c-type natriuretic peptide terminal（c-type natrietic peptide,NT-pro CNP）and their linear relationship with growth were observed before and after treatment.3.To analyze the clinical factors that may affect the therapeutic effect of rhGH.Methods:To collect the diagnosis from January 2018 to October 2019 at the Children Endocrine Clinic of the First People’s Hospital of Changde City And the treatment time≥June for 88 children（41 males,47 females,mean age 8.25±3.10 years）with short stature as the study object.They were divided into GHD（25 males,22 females,mean age 8.27±2.62 years）and ISS（16 males,25 females,mean age 8.18±3.64 years）groups according to etiology.Both groups were subcutaneously injected once rhGH night before bedtime at the recommended dose.Collect the basic clinical data of the children before admission,the children in the treatment of 3 months,the treatment of 6 months after the outpatient follow-up,The height（height,Ht）,weight（weight,Wt）,height standard deviation integral（height standard deviation of points,Ht SDS）,parental genetic target height（mid-parental height,MPH）,and serum IGF-1,thyrotropin（thyroid-stimulating hormone,TSH）,free triiodide adenosine（free three iodine armour gland original acid,FT3）,free thyroxine（FT4）,FBG,uric acid,BAP,OC,NT-pro CNP,etc.The left hand bone age tablets were taken before treatment and 6 months before treatment.a growth hormone excitation test was performed before treatment.Bone age maturity（BAI）,height standard deviation score（height standard deviation of points,Ht SDS）,body mass index（BMI）,growth rate（growth velocity,GV）,parent genetic median height（MPH）,etc.Results:1.Comparison of growth parameters and serological indexes between the two groups:The age and sex of the two groups matched.The growth index Ht SDS、BAI,serum GH peak and IGF-1、serum uric acid level in the ISS group were significantly higher than those in the group（P<0.05）,and there was no statistical difference between the two groups（P>0.05）.2.Comparison of growth parameters between the two groups before and after rhGH treatment:（1）The Ht、Ht SDS、GV of 3 and 6 months of treatment in GHD and ISS groups were significantly higher than before treatment,and the above growth parameters were significantly higher than those of 3 months at 6 months of treatment（P<0.05）.There was no significant difference in the BMI、BAI after treatment between the two groups compared with that before treatment（P>0.05）.（2）The children in GHD group were treated for 0-3 months△Ht、△Ht SDS、GV better than3-6 months（P<0.05）,while the△Ht、△Ht SDS、GV of 3-6 months of treatment in ISS group was better than that of 0-3 months（P<0.05）.（3）The△Ht、GV of 0-3 months in GHD group was significantly higher than that in ISS group（P<0.05）,and the△Ht、GV of 0-6 months was signifi-cantly higher than that in ISS group（P>0.05）.The BMI of 3 months and 6 months in ISS group was significantly higher than that in GHD group（P<0.05）.3.Comparison of serum indexes before and after treatment:（1）serum IGF-1、BAP、OC、NT-pro CNP concentrations in GHD and ISS groups for3 to 6 months were significantly higher than those before treatment（P<0.05）,and at 6 months of treatment were significantly higher than those for 3 months（P<0.05）.（2）Serum uric acid levels were significantly higher in the GHD group after 3 to 6 months of treatment than before（P<0.05）,and slightly higher at 6 months of treatment than at 3 months of treatment（P<0.05）.The serum uric acid level in ISS group was signifi-cantly higher after 3 and 6 months of treatment than before and there was no significant difference in serum FBG level between the two groups before and after treatment（P>0.05）.（3）The serum FT4 levels of the two groups decreased three or six months after treatment,while the FT3/FT4ratio increased higher than before treatment（P<0.05）.There was no statistical difference in TSH and FT3 levels between the two groups before and after treatment（P>0.05）.（4）The serum uric acid value of ISS group was significantly higher than that of GHD group（P<0.05）.4.Analysis of the correlation between growth efficacy and clinical indicators in two groups:（1）GHD group showed positive correlation with post-treatment△Ht_0-3、△Ht SDS_0-3、GV₃and pre-treatment FT4,egative correlation with peak GH and post-treatment△Ht_0-3、△Ht SDS_0-3、GV₃、IGF-1_0-3.△Ht SDS_0-6was positively correlated with△Ht_0-3、GV₃、△Ht SDS_0-3after treatment,negative correlation with pre-treatment CA、pre-treatment Wt、pre-treatment BMI、pre-treatment IGF-1.（2）The GV₆of ISS group was positively correlated with serum BAP、OC level before and after treatment,and negatively correlated with△Ht_0-3、GV₃、△Ht SDS_0-3、△BMI_0-3、FBG.△Ht SDS_0-6was positively correlated with△Ht_0-3、GV₃、△Ht SDS_0-3changes and pre-treatment BAP、NT-pro CNP.Negative correlation with Ht SDS、BMI、BAI、FBG、serum uric acid before treatment and△BMI_0-3、△IGF-1_0-3after treatment.5.Analysis of influencing factors of growth indexes in two groups:（1）The results of multiple stepwise regression analysis show that GV₃、△IGF-1_0-3is an important factor affecting GV₆in GHD group.GV₃、△BMI_0-3is an important factor affecting GV₆in ISS group.（2）△Ht SDS_0-3、pre-treatment CA is an important influencing factor of GHD group△Ht SDS_0-6.△Ht SDS_0-3is an important influencing factor of△Ht SDS_0-6in the ISS group.Conclusions:1.The domestic rhGH treatment can effectively improve the height growth rate of GHD and ISS children,and the short-term rhGH treatment group is better than the ISS group.the difference of time points in linear growth of rhGH promoting body height is not uniform,GHD group has the best curative effect in March before treatment,and the ISS group has the best curative effect in3-6months treatment.rhGH short-term treatment does not accelerate bone age maturation and has little effect on body mass index.2.The serum IGF-1、bone formation index（BAP、OC、NT-pro CNP）of the children in GHD、ISS group after treatment was higher than that before treatment,which can be used as the key index to monitor the curative effect and adjust the dosage during clinical treatment.rhGH can affect the thyroid hormone,uric acid and blood glucose level in children,it is the key index to observe the side effects,and the safety should be monitored dynamically during the treatment period and special treatment should be given according to the changes of the indicators.3.GV₃、△IGF-1_0-3、△Ht SDS_0-3、pre-treatment CA is an important factor affecting the efficacy of GHD children.△Ht SDS_0-3、GV₃、△BMI_0-3is an important factor affecting the efficacy of children in ISS group.