Study On The Influential Factors Of Serum IGF-1 Levels In Growth Hormone Deficiency Children And The Effects Of Rh Gh Therapy On Thyroid Function In These Children

Objective 1)To explore the correlation between serum insulin-like growth factor-1(IGF-1)levels and gender,age,adolescent status,peak GH levels and body mass index(BMI)in children with isolated growth hormone deficiency(IGHD).2)To investigate the changes in thyroid function during recombinant human growth hormone(rh GH)therapy in euthyroid children with growth hormone deficiency(GHD).Methods 1)96 cases of children aged(6-15)with IGHD were selected from pediatric clinic of Wuhan tongji hospital from May 1st 2015 to April 30 th 2017.Their height,weight,peak GH levels and serum IGF-1 levels before rh GH treatment were measured,and BMI,BMI standard deviation score(BMI SDS)and IGF-1 standard deviation score(IGF-1 SDS)were calculated.Then the correlation between IGF-1 levels and gender,age,adolescent status,peak GH levels and body mass index were explored.2)55 children diagnosed with isolated growth hormone deficiency(IGHD)and then received recombinant human growth hormone therapy from May 1st 2014 to April 30 th 2017 were included in this study.Their anthropometric parameters and serum concentrations of thyrotropin(TSH)and free thyroxine(FT4)were analyzed at baseline and during growth hormone treatment.Then,they were divided into puberty group and pre-puberty group according to whether secondary sexual development occurred at baseline,and the dynamic changes of TSH and FT4 level during the treatment in each group were observed.All data were conducted by SPSS 19.0 software,and P < 0.05 was considered to be statistically significant.Results 1)Gender,age,adolescent status,peak GH levels and BMI of IGHD children all had significant influence on their serum IGF-1 level(P=0.032,P=0.000,P=0.038,P=0.028,P=0.000).2)The children were divided into four groups according to their puberty status and peak GH level,and then the correlation between IGF-1 SDS and BMI SDS was observed in each group.The results showed that there was a significant linear positive correlation between serum IGF-1 SDS and BMI SDS in pre-puberty IGHD children with partial growth hormone deficiency(r=0.358,P=0.000).And there was no correlation between serum IGF-1 SDS and BMI SDS in the other three groups.3)Among the 55 IGHD children treated with rh GH,55 children received rh GH therapy for 6 months,44 for 12 months,32 for 18 months and 16 for 24 months.During the treatment,FT4 level declined below the normal lower limit in none of the children,and transient TSH higher than the normal upper limit occurred in 3 pre-puberty group children at 6,6 and 18 months respectively,and then returned to normal spontaneously,which indicated that GHD children had good safety during rh GH treatment.4)Compared with the baseline TSH level(1.86±0.61)m IU/L,it increased significantly after 6 months(2.36±0.98)m IU/L rh GH treatment(P=0.000),and the TSH level was still higher than the baseline after 12 months(2.08±0.77)m IU/L,18 months(2.29±0.77)m IU/L and 24 months(2.29±0.92)rh GH treatment,the difference were statistical significance(P=0.036,P=0.004,P=0.025).After 6 months of rh GH treatment,the FT4 level(1.19±0.18)ng/dl was lower than the baseline(1.21±0.14)ng/dl,and there was no significant difference(P > 0.05);after 12 months(1.18±0.18)ng/dl,18 months(1.16±0.15)ng/dl and 24 months(1.12±0.17)of rh GH treatment,the level of FT4 continued to decline,with significant difference(P=0.041,P=0.044,P=0.013).5)By comparing TSH and FT4 levels between two groups at baseline,we can see that there is no significant difference in TSH and FT4 levels between pre-puberty group and puberty group(P=0.178,P=0.465).During the course of treatment,in pre-adolescent group,TSH increased significantly(P=0.000)after 6 months rh GH treatment and it was still higher than baseline level in 12,18 and 24 months(P = 0.047,P = 0.002,P = 0.036);and the FT4 level continued to decrease during treatment compared with baseline level,and decreased significantly after 24 months of treatment(P=0.046).The level of FT4 in puberty group was significantly lower than that in baseline only at 12 months of treatment(P=0.044),but there was no significant change in FT4 and TSH during the rest of treatment.Conclusions 1)The serum levels of IGF-1 in children with IGHD are related to gender,age,adolescent status,GH peak and BMI.2)In pre-puberty IGHD children with partial GH deficiency,serum IGF-1 level was positively correlated with BMI.3)During the 6~24 months rh GH treatment,none of the 55 children in this study showed abnormal FT4 level.Only 3 children in the pre-puberty group experienced a transient TSH level upper than the normal limit,which then recovered to normal spontaneously.It showed that rh GH treatment promote growth for IGHD children with a good safety profile.4)GH replacement therapy may affect the metabolism of thyroid hormones in IGHD children.During the treatment,the changes of thyroid function in these children should be monitored regularly,in order to identify and correct the abnormal thyroid function in early stage,in this way,GHD children can achieve catch-up growth.5)Compared with puberty IGHD children,pre-puberty children may be more prone to changes in thyroid hormone levels during rh GH treatment.