Intuitiveness, ease of use, and preference of a prefilled growth hormone injection pen: a noninterventional, randomized, open-label, crossover, comparative usability study of three delivery devices in growth hormone-treated pediatric patients. Growth Hormone Improves Body Composition and Motor Development in Infants with Prader-Willi Syndrome After Six Months One‐year results of growth hormone treatment of short stature in Prader—Willi syndrome Growth hormone treatment of children with Prader‐Willi syndrome affects linear growth and body composition favourably High‐dose growth hormone therapy for short children born small for gestational age Effects of growth hormone treatment on growth and body composition in Prader-Willi syndrome: a preliminary report. The Swedish National Growth Hormone Advisory Group. Treatment with human growth hormone in patients with Prader-Labhart-Willi syndrome reduces body fat and increases muscle mass and physical performance Increased Adrenal Androgen Levels in Patients with Prader-Willi Syndrome Are Associated with Insulin, IGF-I, and Leptin, but Not with Measures of Obesity Absence of growth hormone effects on cognitive function in girls with Turner syndrome. 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) Are Needle-Free Injections a Useful Alternative for Growth Hormone Therapy in Children? Safety and Pharmacokinetics of Growth Hormone Delivered by a New Needle-Free Injection Device Compared to a Fine Gauge Needle Effects of Growth Hormone on Growth, Insulin Resistance and Related Hormones (Ghrelin, Leptin and Adiponectin) in Turner Syndrome A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency Efficacy and safety of a new ready-to-use recombinant human growth hormone solution Growth hormone and body composition in children younger than 2 years with Prader-Willi syndrome. Two years of growth hormone therapy in young children with Prader–Willi syndrome: Physical and neurodevelopmental benefits Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. Recombinant human growth hormone treatment in children with thalassemia major. Psychological aspects of the Canadian randomized controlled trial of human growth hormone and low-dose ethinyl oestradiol in children with Turner syndrome. The Canadian Growth Hormone Advisory Group. A Daily Comprehensive Muscle Training Programme Increases Lean Mass and Spontaneous Activity in Children with Prader-Willi Syndrome after 6 Months Growth hormone treatment of short children born small‐for‐gestational‐age: the Nordic Multicentre Trial Growth Hormone Treatment in Short Children with Intrauterine Growth Retardation Idiopathic short stature: results of a one-year controlled study of human growth hormone treatment. Genentech Collaborative Study Group.
BACKGROUND Growth hormone ( GH ) is used to treat pediatric and adult GH deficiency ( GHD ) and growth failure in , among others , patients with Turner syndrome or children born small for gestational age . To improve treatment adherence , self-injection devices should be easy to learn , easy to use , and well accepted , especially in pediatric patients . Several GH pen devices are available , each with distinct features design ed for specific patient needs . OBJECTIVES This study compared injection time and intuitiveness of a prefilled test injection device ( Norditropin FlexPro , Novo Nordisk A/S , Bagsværd , Denmark ) with those of 2 commercially available durable injection devices ( easypod , Merck Serono SA , Geneva , Switzerl and ; and Genotropin , Pfizer Inc , New York , New York ) in GH-treated pediatric patients .  Dose accuracy , application errors , intuitiveness , usability , device features , ease of learning , ease of use , and overall preference were also assessed . METHODS This noninterventional , r and omized , open-label , crossover study enrolled patients aged ≥10 to < 18 years who were diagnosed with GHD or Turner syndrome or were born small for gestational age . Patients were allocated to an intuitiveness group ( without instruction ) or an instruction group and assigned to 1 of 3 sequences of device testing . For each device , time taken to deliver a mock injection of test medium ( FlexPro ) or GH ( easypod and Genotropin ) into an Eppendorf tube and the delivered dose were measured . Dose accuracy and application errors were assessed by a health care professional . Patients assessed the intuitiveness ( intuitiveness group only ) , device features , ease of learning , ease of use , and overall preference of the devices using question naires . RESULTS Included in the study were 56 patients ( mean [ SD ] age , 13.6 [ 2.1 ] years ; 63 % male ; GHD , 44 patients ; Turner syndrome , 3 ; born small for gestational age , 9 ) : 30 in the intuitiveness group and 26 in the instruction group . In the intuitiveness group , the mean ( SD ) mock injection time was significantly shorter with FlexPro ( 47.0 [ 49.0 ] seconds ) than with the easypod ( 219.2 [ 72.6 ] seconds ; P < 0.001 ) or the Genotropin pen ( 95.1 [ 78.4 ] seconds ; P < 0.01 ) . In the instruction group , injection time was also shortest with FlexPro ( 30.7 [ 10.8 ] seconds vs 59.6 [ 13.1 ] with easypod and 40.7 [ 18.6 ] with the Genotropin pen ; both , P < 0.001 ) . Most patients ( 70 % ) ranked FlexPro as the most intuitive device ( easypod , 0 % ; Genotropin , 30 % ) . In both the intuitiveness and instruction groups , a significantly greater proportion of patients considered FlexPro easiest to learn compared with the easypod and Genotropin devices ( both , P < 0.001 ) , although more patients preferred the easypod or Genotropin devices than FlexPro with regard to appearance ( intuitiveness group : FlexPro , 8 patients ; easypod , 9 ; and Genotropin , 13 ; instruction group : FlexPro , 4 ; easypod , 10 ; and Genotropin , 12 ) and quality ( intuitiveness group : FlexPro , 6 patients ; easypod , 10 ; and Genotropin , 14 ; instruction group : FlexPro , 8 ; easypod , 12 ; and Genotropin , 6 ) , and easy- pod 's delivery feedback feature was preferred by more patients ( intuitiveness group : FlexPro , 8 patients ; easypod , 14 ; Genotropin , 8 ; instruction group : FlexPro , 8 ; easypod , 14 ; and Genotropin , 4 ) . Dose accuracies ( as assessed by weighing the delivered dose and calculating variation in the delivered dose by device ) were 4.6 % with FlexPro , 14.6 % with easypod , and 20.6 % with the Genotropin pen in the intuitiveness group , and 2.7 % with FlexPro , 5.8 % with easypod , and 24.4 % with the Genotropin pen in the instruction group . CONCLUSION In this study , Norditropin FlexPro was associated with shorter injection times , higher dose accuracy , and greater intuitiveness , and was rated as easier to learn compared with the easypod and Genotropin devices BACKGROUND Infants with Prader-Willi syndrome ( PWS ) show abnormalities of body composition .  Children with PWS treated with growth hormone ( GH ) demonstrate improved body composition and motor skills . OBJECTIVE To assess body composition and motor changes in infants with PWS following 6 months GH therapy . METHODS Twenty-five infants with PWS ( mean age 15.5 mo ) underwent dual energy X-ray absorptiometry ( DEXA ) assessment of body composition , and motor assessment with the Toddler Infant Motor Evaluation ( TIME ) . Patients were then r and omized to treatment ( Genotropin , 1 mg/m2/day ) or control , with re assessment at 6 months . RESULTS GH treatment significantly increased lean body mass ( 6.4 + /- 2.4 kg to 8.9 + /- 2.7 kg ) and decreased body fat ( 27.6 + /- 9.9 % to 22.4 + /- 10.3 % ) . Age equivalent motor scores improved 4 months in the treated group vs 2 months in controls ( p < 0.01 ) . CONCLUSIONS Infants with PWS show significant body composition and motor development improvement following 6 months GH therapy . We are investigating whether this improvement leads to long-term reductions in obesity At least part of the short stature in Prader — Willi syndrome may be explained by a decreased growth hormone ( GH ) secretory capacity , which occurs in most patients . To study the effects of exogenous GH on growth and body composition , 17 prepubertal children with Prader — Willi syndrome , with a short projected final height , were r and omized to a control group ( n = 9 ) or a treatment group ( n = 8) . Children in the treatment group received GH ( 0.15 IU/kg/day s.c . ) for 1 year . One patient in the treatment group developed pseudotumor cerebri , which resolved after discontinuation of GH ; this patient was omitted from further analysis . After 1 year , height velocity in the GH‐treated group was significantly increased ( + 5.5 SD ) compared with reference values for normal healthy children , whereas there was a decrease in the control group ( –2.3 SD ) . The difference in height velocity between the treated and control groups was significant ( p = 0.0012 ) . Concentrations of both insulin‐like growth factor I ( IGF‐I ) and IGF‐binding protein‐3 increased significantly in the GH‐treated group ( p < 0.008 ) . A gain in height was noted for chronological age ( + 1.07 SD ) after 1 year of GH treatment . Height gain ( + 1.02 SD ) remained unchanged when analysed in relation to bone age . No differences between the groups were found for parameters of weight and body composition . In conclusion , although GH appears to have beneficial effects on height , long‐term studies are necessary before recommendations can be made concerning GH treatment in children with Prader — Willi syndrome . □ Body composition , growth , growth hormone treatment , height velocity , insulin‐like growth factor‐binding protein‐3 , insulin‐like growth factor I , Prader — Willi syndrome , We have compared the growth and the body composition in children with Prader‐Willi syndrome ( PWS ) with and without growth hormone treatment ( recombinant GH 0.1 IU/kg/day ) after a 1‐y period . Twenty‐nine prepubertal children with PWS , with mean body mass index ( BMI ) SDS of 2.2 , and 10 ( control ) healthy obese children with mean BMI SDS of 5.6 , underwent 24‐h frequent blood sampling . Both PWS and control obese children had low and similar GH levels ( 0.7 /ng/l ± 0.4 SD ) . Serum IGF‐I levels , however , were significantly lower in children with PWS ( ‐1.5 SDS ± 0.8 SD vs ‐0.2 SDS ±0.8 SD ) . The 29 PWS children were r and omized into 2 groups of 15 and 14 subjects for GH treatment and no treatment  , respectively . Height velocity increased from ‐1.9 SDS to + 6.0 SDS in the treated group ( p < 0:001 ) and decreased from ‐0.1 SDS to ‐1.4 SDS in the control PWS group during the study year . BMI decreased significantly for the treated group ( + 3.0 SDS to + 2.0 SDS ) . Relative fat mass decreased significantly , while fat‐free mass increased ( p < 0:001 ) for the treated group . No significant changes were noticed in body composition in the control PWS group . In conclusion , the low spontaneous 24‐h GH secretion , regardless of body weight , and the exceptional response to growth hormone treatment together with the finding of low IGF‐I levels suggest that growth hormone deficiency is a common feature of PWS , as a result of hypothalamic dysfunction . Treatment with growth hormone is beneficial for the majority of PWS children The growth-promoting effect of recombinant human growth hormone ( GH ; Genotropin ' ) therapy in short children born small for gestational age was evaluated in a r and omized , open-labelled , multicentre trial . Three parallel groups were recruited : group 1 was an untreated control group ; group 2 received  recombinant human GH , 0.2 IU/kg/day s.c . , and group 3 received recombinant human GH , 0.3 IU/kg/day S.C. Treatment was continued for 24 months . The inclusion criteria were : weight and /or length at birth below -2 SD for gestational age ; chronological age 2 - 8 years ; height/chronological age below -2.5 SD ; height velocity below + 1 SD ; and a serum G H concentration of at least 10 & I after exercise , glucagon administration or insulin-induced hypoglycaemia . The dose of G H was adjusted for body weight every 6 months . Preliminary 18-month data from 46 of the 51 children followed are reported here . This cohort consists of short children who suffered from idiopathic or non-syndromic intrauterine growth retardation ( n = 31 ) and children with either Silver-Russell syndrome ( n = 9 ) , Dubowitz syndrome ( n = 3 ) or fetal alcohol syndrome ( n = 3 ) .  Weight at birth was 1.99 k 0.08 kg ( mean i SEM ) , length at birth was 42.4 k 0.6 cm and gestational age was 37.9 f 4 weeks . At the start of the study , chronological age was 5.1 k 0.3 years , bone age ( Tanner-Whitehouse 2 method ) 3.9 k 0.3 years , height velocity 6.9 k 0.3 cdyears , height velocity for chronological age -0.7 i 0.1 SD , height for chronological age -3.5 k 0.1 SD , and height for bone age -1.5 k 0.3 SD . At the start , groups 1 , 2 and 3 did not differ significantly for any of the variables assessed . Salient 18-month growth data are summarized in Table 1 . The recombinant human GH therapy did not appear to be associated with any clinical adverse events . All children remained prepubertal during the study period . The fasting serum insulin concentrations were measured after 12 months and were found to be twice as high in children treated with G H ( approximately 20 mU/l ) compared with pretreatment levels or with those of untreated children A controlled , r and omized study was conducted to assess the effect of growth hormone ( GH ) treatment on growth , body composition and behaviour in prepubertal children ( 3 - 12 years of age ) with Prader-Willi syndrome .  GH treatment was given to one group of 15 patients ( group A ) at a dose of 0.1 IU/kg/day for 2 years . The second group ( group B ; n = 12 ) was not treated for the first year and was then given GH at a dose of 0.2 IU/kg/day for the second year . All patients had low 24-hour levels of GH and insulin-like growth factor I before GH treatment .  Height velocity SDS increased from -1.9 + /- 2.0 to 6.0 + /- 3.2 during the first year of GH treatment in group A , and from -1.4 + /- 1.2 to 10.1 + /- 3.9 in the second year of the study in group B. When GH treatment was stopped , height velocity declined dramatically . Height SDS followed a similar pattern . GH treatment reduced the percentage body fat and increased the muscle area of the thigh . Isometric muscle strength was also increased . In addition , GH treatment appeared to have psychological and behavioural benefits , which were reversed after cessation of treatment . It was concluded that GH treatment improves growth , body composition and behaviour in children with Prader-Willi syndrome Twelve children with documented Prader-Labhart-Willi syndrome were treated with human growth hormone ( 24 U/m2/week ) during 1 year . The children were divided into three groups : group 1 : overweight and prepubertal ( n = 6 , age 3.8–7.0 years ) ; group 2 : underweight and prepubertal ( n = 3 , age 0.6–4.1 years ) ; group 3 : pubertal ( n = 3 , age 9.2–14.6 years ) . In group 1 , height increased from -1.7 SD to -0.6 SD , while weight decreased from 1.1 SD to 0.4 SD , with a dramatic drop in weight for height from 3.8 SD to 1.2 SD . H and length increased from -1.5 SD to -0.4 SD and foot length from -2.5 SD to -1.4 SD . Body fat , measured by dual X-ray energy absorptiometry , dropped by a third , whereas muscle mass increased by a fourth . Physical capability ( Wingate test ) improved considerably . The children were reported to be much more active and capable . In group 2 , similar changes were seen , but weight for height increased , probably because muscle mass increase exceeded fat mass decrease . Changes in group 3 were similar as in group 1 , even though far less distinct . Conclusion Growth hormone treatment in Prader-Labhart-Willi syndrome led to dramatic changes : distinct increase in growth velocity , height and muscle mass , as well as an improvement in physical performance . Fat mass and weight for height decreased in the initially overweight children , and weight for height increased in underweight children Background / Aim : Since hyper and rogenism in simple obesity is assumed to arise from hyperinsulinism and /or increased insulin-like growth factor I ( IGF-I ) or leptin levels , we examined how in patients with Prader-Willi syndrome ( PWS ) , the most frequent form of syndromal obesity , the accelerated adrenarche can be explained despite hypothalamic-pituitary insufficiency with low levels of insulin and IGF-I. Methods : In 23 children with PWS and a mean age of 5.6 years , height , weight , fat mass , fasting insulin concentration , insulin resistance ( by HOMA-R ; see text ) , and leptin and IGF-I levels were determined to test whether they explain the variance of the levels of dehydroepi and rosterone ( DHEA ) and its sulfate ( DHEAS ) , of and rostenedione , and of cortisol before and during 42 months of therapy with growth hormone . Results : The baseline DHEAS , DHEA , and and rostenedione concentrations were increased as compared with age-related reference values , whereas the cortisol level was always normal . During growth hormone treatment , the DHEA concentration further rose , and the cortisol level decreased significantly . The insulin and IGF-I concentrations were low before therapy , while fat mass and leptin level were elevated . The hormonal covariates provided alone or together between 24 and 60 % of the explanation for the variance of adrenal and rogen levels , but the anthropometric variables did not correlate with them . Conclusions : In children with PWS , elevated and rogen levels correlate with hormones that are usually associated with adiposity . However , the lack of direct correlations between disturbed body composition and and rogen levels as well as the increased sensitivity to insulin and IGF-I are abnormalities specific to PWS , potentially caused by the underlying hypothalamic defect Turner syndrome ( TS ) is a genetic disorder characterized by short stature , gonadal dysgenesis , and a particular neurocognitive profile of normally developed language abilities ( particularly verbal IQ ) and impaired visual-spatial and /or visual-perceptual abilities . We have followed a large sample of girls with Turner syndrome who were enrolled in a long-term , double-blind , placebo-controlled trial of the effects of growth hormone ( GH ) treatment on final adult height . This study provides a unique opportunity to prospect ively evaluate the effects of GH treatment on neurocognitive function in this population of girls with Turner syndrome . The GH- and placebo-treated Turner syndrome subjects were well matched for age , treatment duration , race , karyotype , and socioeconomic status . Treatment ( GH or placebo ) duration s ranged from 1 - 7 yr . Whether GH deficiency and /or treatment in childhood and adolescence influences cognitive outcome in short children or GH-children is controversial . The major result of this study was the absence of GH treatment effects on cognitive function in girls with Turner syndrome . Our findings are in agreement with most of the previous studies that found no apparent growth hormone treatment effects on cognitive function in growth-hormone deficient children . We conclude that this study does not support a role for growth hormone in influencing childhood brain development in girls with Turner syndrome . Their characteristic nonverbal neurocognitive deficits were not altered with GH treatment into early adolescence 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 The clinical safety , use and pharmacokinetics of a new needle-free device for delivery of growth hormone ( GH ) were compared with those of conventional needle injection devices . In an open-label , r and omized , 4-period crossover study , 18 healthy adults received single subcutaneous injections of  Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection . Bioequivalence was established between the devices . In a separate open-label , r and omized , multicenter , 2-period crossover study , pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device ( > 95 % used the Genotropin Pen ) . In total , 128/133 patients who were treated completed the study .  Genotropin ZipTip was well tolerated and > 50 % of patients found no difference between the devices for all parameters assessed . After study completion , > 20 % patients preferred to continue using Genotropin ZipTip . Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding , pain , soreness , and bruising , Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection Background : Concomitant evaluation of the metabolic and growth-promoting effects of growth hormone ( GH ) therapy in Turner syndrome ( TS ) may be used in the prediction of the growth response to GH therapy . Aim : To evaluate the metabolic effects of GH therapy  in TS and correlation with the short-term growth response . Patients : 24 prepubertal children with TS , aged 9.4 ± 2.6 years were followed for auxology and IGF-I , IGFBP-3 , leptin , ghrelin , adiponectin , lipids and OGTT results in a prospect i ve multicenter study . Intervention : GH ( Genotropin ® ) in a dose of 50 µg/kg/day for 1 year . Results : Height st and ard deviation score ( SDS ) increased from –3.9 ± 1.5 to –3.5 ± 1.4 ( p = 0.000 ) on therapy . BMI did not change . IGF-I SDS increased from –2.3 ± 0.4 to –1.6 ± 1.1 at 3 and 6 months ( p = 0.001 ) and decreased thereafter . Serum leptin decreased significantly from 2.3 ± 3.9 to 1.7 ± 5.3 ng/ml ( p = 0.022 ) at 3 months and increased afterwards . Serum ghrelin decreased from 1.2 ± 0.8 to 0.9 ± 0.4 ng/ml ( p = 0.005 ) with no change in adiponectin . Basal and stimulated insulin levels also increased significantly . Δ height SDS over 1 year showed a significant correlation with Δ IGF-I0–3 months ( r = 0.450 , p = 0.027 ) . Conclusion : IGF-I may be considered as a marker of growth response in TS at short term . Leptin shows a decrease at short term but does not have a correlation with growth response . The decrease in ghrelin in face of unchanged weight seems to be associated with increase in IGF-I and insulin levels . The unchanged adiponectin levels in spite of an increase in insulin levels indicates that adiponectin is mainly affected by weight , not insulin Context TransCon Growth Hormone ( GH ) ( Ascendis Pharma ) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency ( GHD ) . Objective To compare the pharmacokinetics , pharmacodynamics , safety , and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD . Design R and omized , open-label , active-controlled study of three doses of weekly TransCon GH versus daily Genotropin ( Pfizer ) . Setting Thirty-eight centers in 14 European countries and Egypt . Patients Prepubertal male and female treatment-naïve children with GHD ( n = 53 ) . Interventions Subjects received one of three TransCon GH doses ( 0.14 , 0.21 , or 0.30 mg GH/kg/wk ) or Genotropin 0.03 mg GH/kg/d for 26 weeks . Main Outcome Measures GH and insulinlike growth factor-1 ( IGF-1 ) levels , growth , adverse events , and immunogenicity . Results Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses . A dose response was observed , with IGF-1 st and ard deviation scores increasing into the normal range for all three TransCon GH doses . Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm , which was not statistically different from 11.6 cm for Genotropin . Adverse events were mild to moderate , and most were unrelated to the study drug . Injection site tolerance was good . One TransCon GH subject developed a low-titer , nonneutralizing antibody response to GH . Conclusions The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH ( pharmacokinetics ) and IGF-1 ( pharmacodynamics ) levels , safety , and efficacy and support advancement into phase 3 development We report 24-month interim results of two multicenter phase III studies in previously untreated children with growth failure secondary to GH deficiency ( GHD ) that were paramount to the development of a new recombinant human GH ( rhGH , somatropin ) , approved as the first ‘ biosimilar ’ in Europe . Study 1 consisted of 3 parts performed in 89 children . The objective was to compare efficacy and safety of the lyophilized formulation of the new somatropin [ Somatropin Powder ( S and oz ) ] with a licensed reference rhGH preparation and the liquid formulation of the new somatropin [ Somatropin Solution ( S and oz ) ] and to assess long-term efficacy and safety of this ready-to-use Somatropin Solution . Study 2 was performed in 51 children and design ed to demonstrate efficacy and safety of Somatropin Powder and to confirm its low immunogenic potential ; rhGH was given sc at a daily dose of 0.03 mg/kg . Primary [ body height , height SD score ( HSDS ) , height velocity , and height velocity ( HV ) SD score ( HVSDS ) ] and secondary [ IGF-I and IGF binding protein 3 ( IGFBP-3 ) ] efficacy end-points and safety parameters were assessed regularly . In study 1 , all treatments showed comparable increases in growth . The baseline-adjusted difference between Somatropin Powder and the reference rhGH product in mean HV was −0.20 cm/yr ( 95 % confidence interval ( CI ) [ −1.34;0.94 ] ) and in mean HVSDS was 0.76 ( 95 % CI [ −0.57;2.10 ] ) after 9 months . These very small differences demonstrate comparable therapeutic efficacy between the two treatments . The results of study 2 were consistent with those seen in study 1 . Equivalent therapeutic efficacy and clinical comparability in terms of safety and immunogenicity between Somatropin Powder and the reference rhGH product and between Somatropin Powder and Somatropin Solution was demonstrated . The safety and immunogenicity profiles were similar and as expected from experience with rhGH preparations OBJECTIVES To assess body composition of infants with Prader-Willi syndrome ( PWS ) by using deuterium dilution and investigating the efficacy of early institution of growth hormone ( GH ) therapy in increasing lean mass ( LM ) and preventing massive obesity . STUDY DESIGN One group of 11 children with PWS < 2 years before and during 30-month GH therapy ( GH group )  was compared with 6 infants administered only coenzyme Q(10 ) for 1 year ( Q10 group ) . LM adjusted for height ( LM(Ht ) ) and relative fat mass ( % FM(Age ) ) st and ard deviation scores ( SDS ) were calculated from data of 95 healthy children . RESULTS Initially , LM(Ht ) of all patients was below the normal average . LM(Ht ) decreased by -0.46 + /- 0.3 SD ( P=.03 ) per year in the Q10 group but rose by 0.25 + /- 0.3 SD ( P=.02 ) per year during GH therapy , normalizing after 30 months ( -0.70 + /- 1.0 SD ) . Despite low to normal weight for height ( WfH ) , % FM(Age ) was above the normal average ( GH group , 31.0 % + /- 4.5 % , Q10 group , 32.4 % + /- 9.5 % ) . In the Q10 infants , % FM(Age ) increased by 0.71 + /- 0.7 SD per year , whereas in the GH group , % FM(Age ) remained more stable up to 30 months . CONCLUSIONS Diminished LM(Ht ) found in infants with PWS further declines during the early years . Early institution of GH therapy lifts LM(Ht ) into the normal range and delays fat tissue accumulation Infants with Prader – Willi syndrome ( PWS ) typically display failure to thrive and decreased muscle mass with excess body fat for age . Growth hormone ( GH ) therapy in children with PWS improves , but does not normalize , body composition and muscle strength and agility . The objective of this study was to determine the effects of earlier GH therapy on anthropometric measurements , body composition , and psychomotor development in affected PWS infants and toddlers . Twenty‐five subjects , ages 4–37 months , were r and omized to 2 years of GH therapy  ( 1 mg/m2/day ) or 1 year of observation without GH treatment and then placed on GH ( 1.5 mg/m2·day ) for 1 year only . Anthropometric measurements were obtained by st and ard methods : percent body fat , lean body mass , and total body bone mineral density by dual x‐ray absorptiometry ; motor constructs of mobility and stability by the Toddler Infant Motor Evaluation ; and cognitive and language function by the Capute Scales of Infant Language and Cognitive Development . GH‐treated PWS subjects demonstrated normalization of length/height st and ard deviation scores ( SDS ) , faster head growth , increased lean body mass accrual , and decreased percent body fat ( P < 0.005 for all parameters ) , as well as improved language ( P = 0.05 ) and cognitive ( P = 0.02 ) quotient Z‐scores compared with similarly aged untreated PWS subjects after 1 year into the study . PWS subjects treated before their first birthday spoke their first words at a mean age of 14.4 ± 2.8 months and walked independently at 23.3 ± 4.8 months . GH  therapy was well‐tolerated ; however , one PWS subject experienced scoliosis progression . As greater benefits were seen in our study with early treatment , prompt referral to a pediatric endocrinologist for consideration of GH therapy is recommended for PWS at an early age . © 2006 Wiley‐Liss , The objective of this study was to investigate the effects of GH administration on pulmonary function , sleep , behavior , cognition , linear growth velocity , body composition , and resting energy expenditure ( REE ) in children with Prader-Willi syndrome . The study used a 12-month , balanced , r and omized , double-blind , placebo-controlled , cross-over experimental design . Twelve subjects were r and omized to GH ( 0.043 mg/kg x d ) or placebo intervention for 6 months and then crossed over to the alternate intervention for 6 months . Differences in outcome variables were determined by paired t tests . Peak flow rate , percentage vital capacity , and forced expiratory flow rate improved and number of hypopnea and apnea events and duration of apnea events trended toward improvement after GH intervention . The only difference in cognition or behavior was an increase in hyperactivity scale on the Behavior Assessment System for Children after GH intervention . Linear growth velocity , REE , and lean mass were higher ( 67 % , 19 % , and 7.6 % , respectively ) , and fat mass and percentage body fat were lower ( 10.3 % and 8.1 % , respectively ) after GH intervention . GH administration did not change mean fasting ghrelin concentration .  GH intervention improved body composition and REE and may contribute to better sleep quality and pulmonary function .  GH administration did not impact fasting ghrelin concentration BACKGROUND To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone ( GH ) in prepubertal thalassemic children with growth retardation . METHODS Twenty thalassemic patients with short stature and delayed bone age were studied . Patients were r and omized into GH-treated ( n = 10 ) and non-GH treated ( control ; n = 10 ) groups . The GH-treated group received recombinant human (rh)-GH ( Genotropin ) at the dose of 0.7 IU/kg per week for 12 months . RESULTS There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing . Following the administration of rhGH , growth velocity increased from 2.47 + /- 0.48 cm/year to 6.27 + /- 0.76 cm/year ( P = 0.005 ) , whereas there was not a similar change in the non-GH-treated group . The height velocities of the two groups during the 1 year follow-up period were significantly different ( 6.27 + /- 0.76 vs 3.99 + /- 0.34 cm/year ; P = 0.025 ) . There were significant differences between the height velocity improvements and height velocity st and ard deviation scores of the two groups as well . CONCLUSION The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height , sexual development and psychological status of girls with Turner syndrome . Girls entering the study were r and omized either to be treated with recombinant human growth hormone or to act as controls . Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years . However , for the purpose s of the psychological study at this time , children receiving oestrogen were excluded from analysis . Girls treated with GH for a period of 2 years showed a significant increase in growth rate , which declined with continued treatment , while the growth rate in the control group remained constant throughout . There was a correlation between the higher growth rate and the girls ' perceptions of themselves as more intelligent , more attractive , having more friends , greater popularity and experiencing less teasing than the untreated group . Growth rate was not correlated with family or school functioning UNLABELLED The reduction of spontaneous physical activity ( PA ) and of muscle tissue are thought to be major causes of fat accretion and metabolic deterioration in Prader-Labhart-Willi syndrome ( PWS ) . We investigated whether a generalized physical training programme in a home setting improves these parameters . The prospect i ve study included 11 prepubertal children ( mean age 8.7 years , range 5.9 - 11.8 ) with documented PWS and under continuous growth hormone treatment for at least 2.8 years . Seven children were enrolled in a training programme for several muscle groups during 4 - 10 minutes daily .  Twelve matched children with PWS served as controls ( average age 8.8 years , 6.1 - 11.3 ) . Before and after training , at 6 months , PA was assessed by measuring  walking distance  by pedometer registration and by an activity score , and body composition by DEXA expressed as st and ard deviation scores ( SDS ) related to height . After training , lean mass ( LM ) increased from -1.83 to -1.48 SDS , p < 0.05 , whereas the controls showed no change . In the training group , walking distance and PA increased from 4.2 to 4.7 km/d and from 255 to 266 points , respectively , and these rises significantly exceeded those observed in controls . CONCLUSION Children with PWS can be motivated by their families to follow a short daily training , which has general effects on PA and does increase , but not normalize LM The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone ( GH ) treatment in prepubertal short children born small‐for‐gestational‐age ( SGA ) . Forty‐eight children born SGA from Sweden , Finl and , Denmark and Norway were r and omly allocated to three groups : a control group of 12 children received no treatment for 2 y , one group was treated with GH at 0.1 IU/kg/d ( n= 16 ) , and one group was treated with GH at 0.2 IU/kg/d ( n= 20 ) . In total 42 children completed 2 y of follow‐up , and 24 children from the treated groups completed 3 y of treatment . Their mean ( SD ) age at the start of the study was 4.69 ( 1.61 ) y and their mean ( SD ) height was ‐3.16 ( 0.70 ) st and ard deviation scores ( SDS ) . The children remained prepubertal during the course of the study . No catch‐up growth was observed in the untreated group , but a clear dose‐dependent growth response was found in the treated children . After the third year of treatment , the group receiving the higher dose of GH , achieved their target height . The major determinants of the growth response were the dose of GH used , the age at the start of treatment ( the younger the child , the better the growth response ) and the family‐corrected individual height deficit ( the higher the deficit , the better the growth response ) . Concentration of insulin‐like growth factor‐I ( IGF‐I ) and IGF‐binding protein‐3 increased during treatment . An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels . GH treatment was well tolerated . In conclusion , short prepubertal children born SGA  show a dose‐dependent growth response  to GH therapy , and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d . However , the long‐term benefit of different regimens of GH treatment in children born SGA remains to be established The aim of this prospect i ve controlled study was to assess the effect of rhGH in short prepubertal children with intrauterine growth retardation and normal growth hormone status . Twenty-six children were r and omized into treatment ( 12F , 4 M ) and control ( 6F , 4 M ) groups . Mean ages were 5.3 ( 1.3 ) yr and 4.3 ( 1.7 ) yr , respectively .  rhGH ( Genotropin ) was used at a dose of 0.2 IU/kg/day as daily s.c . injections for two years . In the treated group , mean height SDS increased from -3.0 ( 0.5 ) to -1.9 ( 0.7 ) and height velocity SDS showed a significant increase from -1.3 ( 2.0 ) to 3.7 ( 1.8 ) in the first year ( p < 0.001 ) and 1.6 ( 1.8 ) ( p < 0.01 ) in the second year of treatment . In the controls , height SDS , initially -2.7 ( 1.4 ) , and height velocity SDS , initially -0.9 ( 1.1 ) , remained essentially the same during two years of follow-up . Height SDS for bone age changed by 0.6 in the treated group and 0.4 in the control group . Target height SDS -- initial height SDS in the treated group improved by 1.1 SD but declined in the control group . IGF-I levels increased from 9.5 ( 4.2 ) nmol/l ( 72 [ 31.8 ] ng/ml ) to 32.5 ( 27.0 ) nmol/l ( 244.4 [ 202.8 ] ng/ml ) ( p = 0.004 ) in the treated group while no change was observed in the controls . No adverse effects were encountered during rhGH therapy . It was concluded that rhGH treatment induces a significant increase in growth velocity in the short term . This outcome , as opposed to the unchanged indices in the control group over the same period , may be indicative of an improved height prognosis in short children born with intrauterine growth retardation treated with rhGH 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
This SR highlights the lack of long-term RCTs reporting final height data and other important qualitative outcomes , such as quality of life .
ABSTRACT Genotropin ( somatropin ) is licensed for the treatment of children with growth hormone deficiency , Prader-Willi syndrome , Turner syndrome , chronic renal insufficiency and in children born small for gestational age .
This systematic review ( SR ) evaluated the clinical efficacy and effectiveness of Genotropin in these conditions to inform a NICE Technology Appraisal of growth hormone for the treatment of growth failure in children .