The Basis for Optimising Growth with Growth Hormone Usage in Children with Idiopathic Short Stature: Analysis of Data from KIGS (Pfizer International Growth Study Database) Adult Height in Children with Idiopathic Short Stature Treated with Growth Hormone Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy. The growth and cardiovascular effects of high dose growth hormone therapy in idiopathic short stature Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. Psychological adaptation in children with idiopathic short stature treated with growth hormone or placebo. Idiopathic short stature: results of a one-year controlled study of human growth hormone treatment. Genentech Collaborative Study Group. The influence of growth hormone (rhGH) therapy on tooth formation in idiopathic short statured children. Quality of life and self-esteem in children treated for idiopathic short stature.
Many children with idiopathic short stature ( ISS ) remain short as adults . Height can be improved permanently by growth hormone ( GH ) treatment , as in children with Turner syndrome or born small for gestational age . Although GH treatment for ISS is an approved indication in the United States , there is ongoing controversy in Europe about approving GH treatment for this indication as well as determining the optimal mode of treatment . In addition to data from r and omized controlled trials , data from pharmacoepidemiological surveys such as the Pfizer International Growth Study Data base ( KIGS ) have provided substantial information about the short-term and long-term effects of GH on growth and adult height in children with ISS . Based on published articles and a recent survey from KIGS on 454 patients who have reached adult height , we attempted to categorize those children with ISS who have the greatest chances of achieving a normal adult height , or at least gain the most height following GH treatment . This analysis provides a rational basis for discussion about the most efficacious and cost-effective uses of GH treatment in children with ISS Idiopathic short stature ( ISS ) includes a heterogeneous group of patients with common characteristics to those of familial short stature and constitutional delay . Some authors state that these children can often respond to GH treatment , thus increasing their adult height . The aims of this study were to determine the effect of GH treatment ( 0.5 - 0.7 IU/kg/week ) and the influence of some initial variables on adult height in patients with ISS . It was a non-r and omized , observational study of 30 boys with ISS and a historical control group of 42 patients . The patients were followed until achieving their adult height . The mean height gain of the treated group attributable to GH was 4.5 cm . A stepwise regression model considering predicted adult height and target height as independent variables and final height as dependent variable gave an R2 coefficient of 0.38 . We conclude that GH significantly increases final height in boys with ISS Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height . It is yet unknown whether therapy would alter pubertal development or affect final height . Three-year treatment results in a group of children with idiopathic short stature are reported . For year 1 of the study , 121 prepubertal children were r and omly selected to receive somatotropin , 0.3 mg/kg per week , administered subcutaneously three times weekly ( n = 63 ) , or to be nontreatment control subjects ( n = 58 ) . After 1 year , all subjects were again r and omly selected to receive either three-times-weekly or daily dosing at the same total dose . For the 92 subjects who completed 36 months of treatment , mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment . Daily dosing result ed in a significantly faster mean growth rate ( 9.0 cm/yr ) than three-times-weekly dosing ( 7.8 cm/yr ) ( p = 0.0005 ) . Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3 , respectively , and did not differ by dosing group . Mean st and ardized height for all subjects improved from -2.7 to -1.6 after 3 years . When the growth rate was st and ardized for bone age , however , subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period ( p < 0.02 ) . Mean st and ardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset , but for individuals this score was more variable . Year-1 growth response , expressed as growth rate or change in height SD score , was the best predictor of growth in subsequent years . Responses to therapy could not be reliably predicted from baseline anthropometric variables , plasma insulin-like growth factor I SD score , growth hormone levels . Final height assessment will be needed to determine the ultimate benefit of therapy OBJECTIVE It Is possible that high dose GH treatment may have beneficial effects on growth but important adverse effects on cardiac function . We have therefore Investigated the efficacy and cardiovascular effects of high dose biosynthetic human GH ( r‐hGH ) treatment in children with idiopathic short stature and a normal pretreatment height velocity GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height < or = -2.5 sd score ( SDS ) ] received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P < 0.02 ; 95 % confidence interval , 0.10 - 0.92 SDS ) . A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P < 0.001 ; 95 % confidence interval , 0.22 - 0.82 SDS ) and no important dropout bias . In conclusion , GH treatment increases adult height in peripubertal children with marked idiopathic short stature The influence of short stature on psychological adaptation in childhood and adolescence is controversial . GH is currently used to treat children with idiopathic short stature ( ISS , also known as non-GH-deficient short stature ) . This study represents the first double-blind , placebo-controlled trial of the effects of GH on the psychological adaptation of children and adolescents with ISS , treated with GH until adult height was attained . Sixty-eight children ( 53 males , 15 females ) , 9 - 16 yr old , with marked ISS ( measured height or predicted adult height -2.5 sd or less ) received either GH 0.074 mg/kg or placebo sc three times per week until height velocity decreased to less than 1.5 cm/yr . Parents completed the  Child Behavior Checklist ( CBCL ) and children the Self-Perception Profile ( SPP ) and Silhouette Apperception Technique at baseline and annually thereafter . Baseline behavioral/emotional adjustment ( CBCL ) and self-concept ( SPP ) scores for children with ISS were within the normative range . The two study groups exhibited similar behavioral and self-concept profiles ( CBCL ) during the first 2 yr of the study . However , CBCL behavior problems ( internalizing , externalizing , and total problems ) appeared to decline , in yr 3 and 4 , in the GH-treated group relative to the placebo-treated group . Group differences in CBCL competency domains and the SPP were not observed at any point during the study . Short stature among children with ISS enrolled in this long-term , placebo-controlled study was not associated with problems in psychological adaptation or self-concept with the psychological instruments employed . GH treatment was associated with a trend toward improvement in problem behaviors , as measured by question naires ( CBCL ) completed by study participants ' parents . It remains to be determined whether GH treatment significantly impacts adaptation , psychosocial function , or quality of life in children with ISS A multicenter r and omized trial of human growth hormone treatment was carried out in 121 children with short stature who did not meet the classic criteria for growth hormone deficiency . Patients treated for 1 year with recombinant somatropin , 0.1 mg/kg three times a week , had a significant increase in mean growth rate from 4.6 + /- 1.1 to 7.5 + /- 1.2 cm/yr , whereas untreated children 's growth rate did not change significantly ( 4.2 + /- 1.3 vs 5.0 + /- 1.4 cm/yr ) . There was a 1-year advance in bone age for each group ; thus there was a significant increase in the predicted height of the treated but not the control group . Among the treated children , the growth response did not differ among those classified on the basis of parental height and bone age as having familial short stature or constitutional delay of growth and development . Pre study anthropomorphic features were not related to subsequent growth in either the treated or control groups . The baseline plasma insulin-like growth factor I concentration was inversely related to the growth response to growth hormone treatment ( r = -0.50 , p = 0.0003 ) . By contrast , the serum growth hormone concentration measured in sample s obtained at 20-minute intervals for 12 or 24 hours or after clonidine administration did not predict the future growth rate . There were no side effects of growth hormone treatment . The results suggest that children who have significant short stature and slow growth may benefit from a trial of growth hormone therapy The purpose of this preliminary study was to evaluate tooth formation in children with idiopathic short stature , before and during treatment with recombinant growth hormone ( rhGH ) . Twenty-nine short-statured children ages 6 to 13 years were assigned into two treatment groups , an " experimental " group ( n = 18 ) , which received rhGH , and a " control " group ( n = 11 ) , which was observed for 1 year before commencing rhGH  treatment . Clinical and radiographic records were obtained at the initial , year 1 , and year 2 visits . Tooth formation and stature were assessed by calculating Z-scores , appropriate for the age and gender of each child . Delta-Z scores , which measure the change in Z-score over time , were also calculated between annual visits . Height was measured and recorded every 3 months , and Z-score statural norms for age and gender were derived from the 1977 National Center for Health Services national probability sampling . Tooth formation st and ards were derived from Moorrees et al. A matched control sample for tooth development was derived from untreated children . Tooth formation was initially delayed although the degree of reduction in stature exceeded the initial degree of delay in tooth formation . During this 2-year study , rhGH therapy had a significant influence on acceleration or gain in stature , but did not have a significant influence on tooth formation OBJECTIVE Changes in health-related quality of life ( HRQOL ) and self-esteem were studied in children with idiopathic short stature ( ISS ) participating in a study on the effect of growth hormone treatment .  STUDY DESIGN Prepubertal children ( n = 36 ) with ISS were r and omly assigned to a treatment or control group .  Children with ISS , their parents , and the pediatrician completed  HRQOL and self-esteem question naires 3 times in 2 years . RESULTS At the start , children with ISS did not have lower scores than the norm population , except for social functioning HRQOL . The pediatrician reported an improvement of HRQOL in the treatment group , the parents reported no change , and the children in the treatment group reported the same , or sometimes even worse , HRQOL or self-esteem than the control group . Changes related to the child 's satisfaction with height and hardly to growth itself . CONCLUSION The assumption that growth hormone treatment improves HRQOL in children with ISS could not be supported in this study
CONCLUSIONS Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults , although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed .
OBJECTIVE To systematic ally determine the impact of growth hormone therapy on adult height of children with idiopathic short stature .