Analysis of the influencing factors of recombinant human growth hormone effect in the children with Turner syndrome / 中华儿科杂志

ABSTRACT

Objective@#To analyze the clinical data, karyotype, growth hormone receptor (GHR) exon 3 polymorphism, etc. in Turner syndrome before and after recombinant human growth hormone (rhGH) treatment, and thereby to understand the related factors influencing the rhGH curative effect in children with Turner syndrome.@*Methods@#This was a retrospective study of 31 cases with Turner syndrome who were treated with growth hormone for more than 1 year in the pediatric outpatient department of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2010 to January 2017. The GHR Exon3 polymorphism was detected by PCR assay, Turner syndrome children were divided according to GHR exon3 genotype for homozygous for the full-length GHR isoform (fl/fl-GHR)and carriers of one or two copies of the GHR exon3 allele(fl/d3-GHR;d3/d3-GHR).According to the karyotype, the children were divided into 45,X karyotype group and other karyotype group. The height standard deviation (Ht-SDS) and growth velocity (GV) as indicators to measure rhGH treatment efficacy, the data were analyzed by the SPSS12.0 software (t test, one-way ANOVA and multiple linear regression analysis).@*Results@#(1) The mean age at diagnosis of 31 cases was (12.2±2.9) years, the bone age was (8.9±2.4) years, the height was (126.2±10.5) cm and the Ht-SDS was (-3.5±1.3) SDS. The karyotype was 45,X in 14 patients, 17 cases had other karyotypes. Thirteen cases were of (fl/fl-GHR) (42%), 14 cases of fl/d3-GHR (45%) and 4 cases of d3/d3-GHR(13%).Among the 31 cases, the main reason for 5 patients' hospitalization was no secondary sexual characteristics, another 26 cases had short stature (accounting for 81%).(2) After Growth hormone treatment, growth rate (cm/year)(7.3±1.4, 7.0±3.0, 7.0±1.3) and Ht-SDS (-2.8±1.2, -2.5±0.9, -2.2±0.8) were significantly higher than the pre-treatment levels (2.9±0.9, -3.5±1.3), the difference was statistically significant (F=54.12, 4.43, P<0.05) ; the third year Ht-SDS(-2.2±0.8)higher than the first year Ht-SDS(-2.8±1.2), the difference was statistically significant (t=-2.3, P<0.05) .(3)Before rhGH treatment, the height of 45,X karyotype group was significantly lower than that of other karyotypes ((122.1±9.1) cm vs. (129.9±10.3) cm, t=-2.2, P<0.05)). Before and after rhGH treatment, there was no significant difference in growth rate (cm/year) and Ht-SDS, between 45, X karyotype group and other karyotype group, but with the prolongation of treatment time, the Ht-SDS of other karyotype groups had an improvement trend compared with the 45,X karyotype groups. (4) After short-term and long-term treatment with rhGH, there were no significant differences in GV, Ht-SDS between patients with different genotypes (P>0.05). (5) Multivariate linear regression analysis showed that ΔHt-SDS was negatively correlated with the age at initial treatment(partial regression coefficient=-0.098, P <0.05), and positively correlated with GV before treatment(partial regression coefficient=0.202, P<0.05).@*Conclusions@#In Turner's syndrome children, the earlier the rhGH treatment started, the faster the growth rate before treatment and the longer treatment duration, the better effect of rhGH treatment was obtained. Before rhGH treatment, the height of 45,X karyotype group was significantly lower than that of other karyotypes. Before and after rhGH treatment, there was no significant difference in growth rate (cm/year) and Ht-SDS, but with the prolongation of treatment time, the Ht-SDS of other karyotype groups had an improvement trend compared with the 45,X karyotype groups. GHR exon 3 polymorphism did not significantly affect the efficacy of rhGH in Turner syndrome children, but large-scale long-term studies are still needed.