title: Growth Hormone Improves Body Composition and Motor Development in Infants with Prader-Willi Syndrome After Six Months Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation Clinical Effects of Treatment for Hypogonadism in Male Adolescents with Prader-Labhart-Willi Syndrome A Randomised Study of Two Doses of Biosynthetic Human Growth Hormone on Final Height of Pubertal Children with Growth Hormone Deficiency Increased Adrenal Androgen Levels in Patients with Prader-Willi Syndrome Are Associated with Insulin, IGF-I, and Leptin, but Not with Measures of Obesity 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. Two years of growth hormone therapy in young children with Prader–Willi syndrome: Physical and neurodevelopmental benefits Effects of Growth Hormone on Growth, Insulin Resistance and Related Hormones (Ghrelin, Leptin and Adiponectin) in Turner Syndrome Growth Hormone Treatment in Short Children with Intrauterine Growth Retardation High‐dose growth hormone therapy for short children born small for gestational age A Daily Comprehensive Muscle Training Programme Increases Lean Mass and Spontaneous Activity in Children with Prader-Willi Syndrome after 6 Months Growth hormone improves mobility and body composition in infants and toddlers with Prader-Willi syndrome. The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients. Final Height in Short Children Born Small for Gestational Age Treated with Growth Hormone Efficacy and safety of a new ready-to-use recombinant human growth hormone solution Adiponectin levels in prepubertal children with Prader-Willi syndrome before and during growth hormone therapy. Efficacy and Safety of Growth Hormone Treatment in Children Born Small for Gestational Age in Japan Growth impairment shows an age-dependent pattern in boys with chronic kidney disease Prevalence of Autoantibodies Associated with Thyroid and Celiac Disease in Ullrich-Turner Syndrome in Relation to Adult Height After Growth Hormone Treatment Early, discontinuous, high dose growth hormone treatment to normalize height and weight of short children born small for gestational age: results over 6 years. Growth hormone treatment and fat redistribution in children born small for gestational age. Effect of Different Growth Hormone Dosages on the Growth Velocity in Children Born Small for Gestational Age Auxology and response to growth hormone treatment of patients with intrauterine growth retardation or Silver‐Russell syndrome: analysis of data from the Kabi Pharmacia International Growth Study Recombinant human growth hormone in short children born small for gestational age. German Study Group. One‐year results of growth hormone treatment of short stature in Prader—Willi syndrome A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis Effect of 2 years of high-dose growth hormone therapy on cognitive and psychosocial development in short children born small for gestational age. Growth hormone treatment of short children born small‐for‐gestational‐age: the Nordic Multicentre Trial Growth hormone treatment of children with Prader‐Willi syndrome affects linear growth and body composition favourably Early treatment with GH alone in Turner syndrome: prepubertal catch-up growth and waning effect. 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 pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. Results and side‐effects of treating children with growth hormone after kidney transplantation – a preliminary report Short boys treated with growth hormone show normal progression of testicular size and achieve normal serum testosterone concentrations. Growth hormone treatment on atherosclerosis: results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. Response to Growth Hormone with Respect to Pubertal Status on Increased Dose in Idiopathic Growth Hormone Deficiency: An Analysis of Turkish Children in the KIGS Database (Pfizer International Growth Study) Quality of life and psychological well-being in GH-treated, adult PWS patients: a longitudinal study. Growth hormone and body composition in children younger than 2 years with Prader-Willi syndrome. Effects of growth hormone treatment on growth and body composition in Prader-Willi syndrome: a preliminary report. The Swedish National Growth Hormone Advisory Group. A longitudinal study of craniofacial growth in idiopathic short stature and growth hormone-deficient boys treated with growth hormone. High-dose growth hormone (GH) treatment in non-GH-deficient children born small for gestational age induces growth responses related to pretreatment GH secretion and associated with a reversible decrease in insulin sensitivity. Normal Progression of Testicular Size in Boys with Idiopathic Short Stature and Isolated Growth Hormone Deficiency Treated with Growth Hormone: Experience from the KIGS
abstract: 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 A total of 130 short children were included in a French multicentre study and r and omized between a control group ( group A ) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week ( group B ) and 1.4 IU/kg/week ( group C ) for 2 years . Height velocity was significantly increased ( p<0.0005 ) in groups B and C , with a greater increase in group C than in group B ( p < 0.001 ) . The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy . These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR , and that this effect is dose dependent . The effect on final height has still to be demonstrated Background : In boys with Prader-Labhart-Willi syndrome ( PWS ) , hypogonadism causes pubertal arrest and reduces pubertal muscle growth . Formerly , it was assumed that therapy with gonadal hormones accentuates behaviour abnormalities in PWS . Our aim was to assess the clinical effects of human chorionic gonadotropin ( hCG ) therapy on pubertal development , muscle mass and behaviour in adolescents with PWS . Methods : 6 peripubertal boys with PWS undergoing long-term treatment with growth hormone  were examined 6-monthly for at least 2 years before and after pubertal arrest ( 13.5 ± 0.3 years , mean ± SEM ) and the beginning of hCG therapy ( 500–1,500 IU twice weekly , intramuscularly ) . Height , weight , pubertal stage , bone age , body composition ( by dual-energy X-ray absorptiometry ) , testosterone levels and behaviour abnormalities ( obtained from parents ) were assessed . Results : Testicular volume and lean mass were reduced in pubertal boys with PWS . During hCG therapy , testosterone levels and lean mass significantly increased ( at the beginning and after 2 years of hCG therapy : 2.3 ± 0.9 and 10.7 ± 1.3 nmol/l , –3.1 ± 0.3 and –1.4 ± 0.6 SD , respectively ) , and fat mass stabilized at 38 % . The characteristically observed PWS-associated problems , mood instability , aggressiveness and difficulties in social interaction , did not deteriorate during therapy . Conclusion : In the present study , timely application of hCG to treat hypogonadism in boys with PWS  promoted virilization and normalized muscle mass without detrimental effects on behaviour . Larger studies comparing hCG therapy with testosterone replacement would be useful Aims : To determine the effectiveness of different doses of r-hGH therapy during puberty in children with growth hormone deficiency ( GHD ) . Methods : R and omized controlled trial of different doses of r-hGH therapy administered during puberty in 49 children with GHD . The patients were allocated r and omly using a r and om number table to one of two groups : group 1 ( 15 IU/m2/week ) or group 2 ( 30 IU/m2/week ) . Patients were included if they had received r-hGH daily at a dose of 15 IU/m2/week ( 0.7 mg/m2/day ) for at least 1 year before r and omization . Results : Height increase st and ard deviation scores ( SDS ) were similar between the two groups ( group 1 : 1.1 ; group 2 : 1.2 ; p = 0.81 ) . Conclusion : A higher dose of r-hGH administered during puberty does not appear to have a significant effect on final height of children with GH deficiency . Altering pubertal tempo or intensifying prepubertal r-hGH therapy may be a more promising approach to improving final height in children with GH deficiency 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 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 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 , 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 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 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 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 OBJECTIVES To determine the effect of growth hormone ( GH ) on body composition and motor development in infants and toddlers with Prader-Willi syndrome ( PWS ) . STUDY DESIGN Twenty-nine subjects with PWS ( 4 - 37 months of age ) were r and omized to GH treatment ( 1mg/m 2 /day ) or observation for 12 months . Percent body fat , lean body mass , and bone mineral density were measured by dual x-ray absorptiometry ; energy expenditure was measured by deuterium dilution ; and motor constructs of mobility ( M ) and stability ( S ) were assessed using the Toddler Infant Motor Evaluation ( TIME ) . RESULTS GH-treated subjects , compared with controls , demonstrated decreased percent body fat ( mean , 22.6 % + /- 8.9 % vs 28.5 % + /- 7.9 % ; P < .001 ) , increased lean body mass ( mean , 9.82 + /- 1.9 kg vs 6.3 + /- 1.9 kg ; P < .001 ) , and increased height velocity Z scores ( mean , 5 . 0 + /- 1.8 vs 1.4 + /- 1.0 ; P < .001 ) . Patients who began GH before 18 months of age showed higher mobility skill acquisition compared with controls within the same age range ( mean increase in raw score , 284 + /- 105 vs 206 + /- 63 ; P < .05 ) . CONCLUSIONS GH treatment of infants and toddlers with PWS for 12 months significantly improves body composition and when begun before 18 months of age increases mobility skill acquisition . These results suggest that GH therapy instituted early in life may lessen deterioration of body composition in PWS while also accelerating motor development CONTEXT The d3/fl-GH receptor ( d3/fl-GHR , exon 3-deleted/full-length GHR ) has recently been associated with responsiveness to GH therapy . OBJECTIVE The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and /or GH therapy-stimulated growth in small-for-gestational-age ( SGA ) patients . DESIGN This was a 2-yr prospect i ve , controlled , r and omized trial . SETTING Thirty Spanish hospitals participated .  Auxologic and GH secretion evaluation was hospital based , whereas molecular analyses and auxologic data computation were central ized . PATIENTS Patients included 170 short SGA children : 140 remained prepubertal and 30 entered puberty during the second follow-up year . INTERVENTION Eighty-six were treated with GH ( 66 microg/kg.d ) for 2 yr and 84 were not treated . MAIN OUTCOME MEASURES Previous and 2-yr follow-up auxologic data were recorded at each hospital , d3/fl-GHR genotypes determined , and data analyzed for patients who remained prepubertal ( group 1 , 68 GH treated and 72 non-GH treated ) and for all the patients ( group 2 ) . RESULTS In group 1 GH-treated patients , growth velocity , and height-sd score during the first and second years , total 2-yr height gain ( 18.5 + /- 2.4 cm in d3/d3 ; 18.4 + /- 2.6 in d3/fl ; 19.5 + /- 2.3 in fl/fl ) , Delta 2-yr height increase ( 9.1 + /- 2.4 cm in d3/d3 ; 9.4 + /- 3.0 in d3/fl ; 10.4 + /- 2.1 in fl/fl ) , first-year growth prediction and studentized residual values ( 0.08 + /- 1.26 in d3/d3 ; 0.28 + /- 1.21 in d3/fl ; 0.67 + /- 0.95 in fl/fl ) did not differ among the d3/fl-GHR genotypes . In group 1 non-GH-treated patients , neither growth velocity nor height-sd score changed significantly , and values were similar in each d3/fl-GHR genotype . Results in all patients ( group 2 ) were similar to those in group 1 . CONCLUSIONS In short non-GH-deficient SGA children , both spontaneous growth rate and responsiveness to 66 microg/k.d GH therapy were similar for each d3/fl-GHR genotype carried The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age ( SGA ) .  GH treatment was begun before puberty and continued to final height ( FH ) . Seventy-seven short ( height SD score below −2 ) prepubertal children born SGA ( below −2 SD for birth weight and /or birth length ) , with a broad range of GH secretory capacity , were treated with GH in a daily dose of 33 μg/kg ( 0.1 U/kg ) , beginning before the onset of puberty . We observed a difference between adult and pretreatment projected height of 1.3 SD ( 9 cm ) for the entire group . Among the children treated for > 2 y before puberty , this mean gain ( i.e. difference ) in final height was 1.7 SD , whereas the mean gain was 0.9 SD among those in whom treatment was begun < 2 y before puberty . Better catch-up growth was observed in the younger ( r = −0.56 , p < 0.0001 ) , shorter ( r = −0.49 , p < 0.0001 ) , and lighter ( r = −0.46 , p < 0.0001 ) subjects . We conclude that GH treatment improves the final height of short children born SGA . The height gain attained before the onset of puberty is maintained to final height . The younger , shorter , and lighter the child at the start of GH treatment , the better the response . Moreover , most of these SGA individuals treated with GH reach their target height 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 CONTEXT Children with Prader-Willi syndrome ( PWS ) may have obesity and an abnormal body composition with a high body fat percentage , even if they have a normal body weight . Adiponectin has been inversely related to obesity and insulin resistance . OBJECTIVE The objective of the study was to evaluate in prepubertal PWS children the following : 1 ) adiponectin levels , body composition , carbohydrate metabolism , and triglyceride levels ; 2 ) associations between adiponectin and body composition , carbohydrate metabolism , and triglycerides ; and 3 ) effects of GH treatment on these outcome measures . PATIENTS Twenty prepubertal PWS children participated in the study . INTERVENTION The subjects were r and omized into a GH treatment group ( n=10 , 1 mg/m2.d ) and a non-GH-treated control group ( n=10 ) . MAIN OUTCOME MEASURES At baseline , after 1 and 2 yr of GH treatment , fasting levels of adiponectin , glucose , insulin , and triglycerides were assessed . Body composition and fat distribution were measured by dual energy x-ray absorptiometry . RESULTS PWS children had significantly higher median ( interquartile range ) adiponectin levels [ 17.1 mg/liter ( 13.9 - 23.2 ) ] than healthy sex- and age-matched controls [ 11.8 mg/liter ( 9.7 - 12.5 ) , P<0.005 ] . Body fat percentage was significantly higher than 0 sd score [ 1.8 sd score ( 1.5 - 2.1 ) , P<0.001 ] . Adiponectin levels were inversely related to triglyceride levels ( r=-0.52 , P=0.03 ) . There was a tendency to an inverse relation with body fat percentage and body mass index , but no correlation with fasting insulin or glucose levels , the insulin to glucose ratio , or homeostasis model assessment index . During GH treatment , adiponectin levels increased significantly and did not change in r and omized controls . CONCLUSION Adiponectin levels were increased , and inversely associated with triglyceride levels , in prepubertal , not overweight PWS children , although they had a relatively high body fat percentage . During GH treatment , adiponectin levels further increased , whereas no change was found in the controls , which is reassuring with respect to the development of insulin resistance during GH treatment Growth-promoting effects and safety of growth hormone ( GH ) treatment in prepubertal short-statured children born small for gestational age ( SGA ) were evaluated in a multicenter , open-label , r and omized parallel-group comparison study . Patients were r and omized to two dose groups ; 34 and 33 patients received GH at 0.033 and 0.067 mg/kg/day for one year , respectively . The increase of the mean height velocity st and ard deviation score ( SDS ) was significantly ( p < 0.0001 ) higher in the 0.067-mg group ( from -1.4 to 4.7 ) than that in the 0.033-mg group ( -1.9 to 2.6 ) . A significant ( p < 0.0001 ) increase in the mean height SDS was established in the 0.067-mg group ; increases of -3.1 to -2.5 vs -3.1 to -2.2 in the 0.033- and 0.067-mg groups , respectively . The trial was non-eventful . Oral glucose tolerance tests indicated a mostly normal pattern of plasma glucose before and after 12-month GH treatment . The growth-promoting effect was significantly higher with GH treatment at 0.067 mg/kg/day The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease ( CKD ) . We have evaluated growth failure by measuring four components of linear growth : body height ( HT ) , sitting height ( SHT ) , arm length ( AL ) and leg length ( LL ) . Data were prospect ively collected for up to 7 years on 190 boys ( 3–21 years old ) with congenital or hereditary CKD ( all had developed at least stage 2 CKD by the age of 10 years ) . Patients showed the most severe growth failure in early childhood , followed by an acceleration in growth in pre-puberty , a slowing-down of growth at puberty , as expected , and thereafter a late speeding-up of growth until early adulthood . This pattern was observed irrespective of the degree of CKD and different treatment modalities , such as conservative treatment , recombinant human growth hormone ( rhGH ) therapy or transplantation . LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD . A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients . This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy A prospect i ve , multicenter study of patients with Ullrich-Turner syndrome ( UTS ) was conducted to estimate the prevalence of autoantibodies to tissue transglutaminase ( tTg ) , thyroid stimulating hormone receptor ( TSH-R ) , thyroglobulin ( TG ) and thyroid peroxidase ( TPO ) in relation to adult height after long-term growth hormone ( GH ) treatment . Out of 347 near-adult ( > 16 years ) patients with UTS from 96 German centers , whose longitudinal growth was documented within the Pharmacia International Growth Study ( KIGS ) , 188 returned for a st and ardized follow-up visit at a median chronological age of 18.7 ( 16.0 - 23.6 ) years ( bone age > 15 years ) . Serum sample s of 120 patients were obtained for central measurements of TSH , thyroxine ( T4 ) and free T4 and autoantibodies by st and ard immunoassays . Information regarding thyroid disease , karyotype and anthropometric data was extracted from the KIGS data base . Thirty-six percent of the patients with UTS had positive TG and /or TPO autoantibodies and 4 % had positive tTg autoantibodies , whereas 2 % had positive TG and /or TPO autoantibodies as well as positive tTg autoantibodies . TSH-R autoantibodies were undetectable in all patients . The detection of autoantibodies was unrelated to a specific karyotype . Median height st and ard deviation scores ( SDS , UTS ) at start of GH treatment ( 0.43 ; -1.07 , 1.85 ) and at follow-up ( 1.36 ; -0.11 , 2.57 ) were comparable in all patients independent of their antibody status . The total deltaheight SDS , however , was higher in patients with negative autoantibody titers ( 1.08 ; -0.03 , 2.25 ) compared to those with positive antibody titers ( 0.68 ; -0.44 , 1.82 ; p < 0.01 ) . Our study confirms the high prevalence of autoantibodies in patients with UTS predisposing them to autoimmune thyroid disease and celiac disease , and indicates for the first time that autoimmune pathologies may interfere with GH therapy and thus compromise final height . Therefore , medical care for patients with UTS should routinely include screening for these autoimmune disorders in order to assure early detection and appropriate treatment Most children born small for gestational age ( SGA ) normalize their size through spontaneous catch-up growth within the first 2 yr after birth . Some SGA children fail to do so and maintain an abnormally short stature throughout childhood . We have previously reported that high dose GH treatment ( 66 or 100 microg/kg x day s.c . over 2 yr ; age at start , 2 - 8 yr ; n = 38 ) induces pronounced catch-up growth in short children born SGA , thereby normalizing their height and weight in childhood . Here , we report on the further prepubertal growth course of these children over the first 4 yr after withdrawal of early , high dose GH treatment . Of the 38 treated children , none developed precocious puberty , and 22 remained prepubertal . Mean age of the latter at start of GH was 4.4 yr , height was -3.7 SD score , and height after adjustment for midparental height was -2.9 SD score . Height increased by an average of 2.5 SD during the 2 yr of GH treatment and decreased by 0.4 and 0.3 SD , respectively , during the first and second year after GH withdrawal . Subsequently , when stature was not extremely short at the start ( mean adjusted height SD score , -2.7 ; n = 13 ) , no further GH treatment was given , and the adjusted height was stabilized around -1.0 SD score ; when stature was very short at the start ( mean adjusted height , -3.3 SD score ; n = 9 ) , a second course of GH treatment ( 66 microg/kg x day s.c . ) was initiated either 2 yr ( n = 5 ) or 3 yr ( n = 4 ) after initial GH withdrawal . This second course was associated with renewed catch-up growth and also result ed in a mean adjusted height of -1.0 SD score . In each subgroup , the pattern of the weight course paralleled that of the height course ; GH treatment was well tolerated . In conclusion , early , discontinuous , high dose GH treatment appears to be a safe and efficient option to normalize prepubertal height and weight in the majority of short SGA children . It remains to be examined whether the normalized stature will be maintained during pubertal development , either with or without further GH treatment OBJECTIVE To determine whether in children born small for gestational age ( SGA ) high-dose growth hormone ( GH ) treatment is not only associated with catch-up of growth and with gain of lean mass , but also with a more central fat distribution . STUDY DESIGN Short children who were SGA ( n = 25 ; age [ mean + /- SD ] , 5.3 + /- 1.5 years ) were r and omly assigned to remain untreated ( n = 14 ) or to receive GH ( n = 11 ; sc 66 mug/Kg/d ) . Growth status and body composition were assessed at the study 's start , after 1 year , and after 2 years with anthropometry and absorptiometry . RESULTS Children who were treated with GH gained more height and weight than children who were untreated and developed a less adipose body composition ( all P < .0001 ) , as expected . However , these changes were also accompanied by a relatively more centripetal distribution of fat mass ( 0 - 2 year change in ratio of trunk fat to limb fat ; 0.26 + /- 0.23 versus 0.02 + /- 0.15 ; P < .0001 ) . CONCLUSION In children who are SGA , catch-up growth induced by exogenous GH in high doses is accompanied by a less adipose body composition and a more central fat distribution To assess whether short-term growth hormone ( GH ) treatment can improve the linear growth in children who were born small for gestational age ( SGA ) , we started a r and omized multicenter trial in 26 age- and sex-matched prepubertal children born SGA . During the 1st year of GH therapy , all children received GH 0.23 mg/kg/week , then during the 2nd year , 13 children received the same dose ( group A ) , and in the other 13 children , the dose of GH was doubled , i.e. , 0.46 mg/kg/week ( group B ) . During the 1st year of therapy , the growth velocity significantly ( p < 0.0001 ) increased in all patients . During the 2nd year , group A showed a significant decrease of the growth velocity ( p < 0.015 ) , whereas group B maintained the growth rate . The height in group A children significantly increased during the 1st and the 2nd year of GH therapy ( p < 0.000002 and p < 0.000001 , respectively ) , reaching the normal range in 8 out of 13 children at the end of 2 years of GH therapy . The height in group B children significantly increased during the 1st and the 2nd year of GH therapy ( p < 0.000001 and p < 0.000001 , respectively ) , reaching the normal range in all 11 children who completed the GH therapy . The height gain was similar in groups A and B treated with the same GH dosage during the 1st year of therapy . A greater increase in height gain was found in children of group B treated with the higher GH dosage during the 2nd year of therapy as compared with group A ( p < 0.02 ) . Significant increases in insulin-like growth factor I ( p < 0.0001 ) , acid-labile subunit ( p < 0.0002 ) , and bone/chronological age ratio ( p < 0.0001 ) were found after the 1st year of GH therapy , but no significant changes were observed during the 2nd year , independently of the GH dose . In conclusion , the height velocity of children born SGA  significantly increases during the 1st year of GH therapy , diminishes , but can decrease during the 2nd year , if the GH dosage is not raised Using the data base from the Kabi Pharmacia International Growth Study , 105 patients with intrauterine growth retardation ( IUGR ) ( 82 males , 23 females ) and 45 with Silver‐Russell syndrome ( SRS ) ( 32 males , 13 females ) with persistent postnatal growth failure were studied . Patients with IUGR had a birth length and birth weight more than 2 SD below the mean for gestational age . Their height deficit at the start of GH treatment was ‐3.0 SDS at a median chronological age of 8.7 years and a median bone age of 7.0 years . Mean paternal and maternal heights were 166 and 153 cm , respectively . The median dose  of GH  was 0.5 IU/kg/week , given at a median frequency of five injections/week . The median height SDS for chronological age after 1 , 2 and 3 years of GH treatment were ‐2.5 , ‐2.1 and ‐1.9 , respectively . In the 45 patients with SRS , median chronological age and median bone age at the start of treatment were 6.7 and 3.2 years , respectively , and mean paternal and maternal heights were 167.5 and 160 cm , respectively . The median dose of GH was 0.7 IU/kg/week , given at a median frequency of six injections/week . The median height SDS for chronological age at the start of treatment and after 1 , 2 and 3 years were ‐3.5 , ‐2.9 , ‐2.8 and ‐2.2 , respectively . Although the criteria used by physicians when diagnosing SRS were not controlled or verified in this study , it appears that patients with SRS can be differentiated from those with IUGR with persistent growth failure by their reduced bone age for chronological age at the start of treatment , and by the fact that patients with SRS tended to be born to parents of normal height  . GH treatment in both groups induced catch‐up growth , though long‐term follow‐up studies will be required to assess the effects of treatment on final height The effects of recombinant human growth hormone ( rhGH ) treatment in 69 prepubertal , non-GH deficient children born small for gestational age ( SGA ) were evaluated over 2 years . At start of the study mean age was 5.1 years , mean bone age was 3.8 years and mean height SDS was -4.0 . The children were r and omly allocated to 3 groups receiving no treatment or daily subcutaneous injections of rhGH at a dose of 0.1 IU/kg body weight ( group 0.1 IU ) or 0.2 IU/kg body weight ( group 0.2 IU ) . At start of the study mean height velocity SDS was -1.4 in the control group , -0.7 in group 0.1 IU and -1.4 in group 0.2 IU . After 2 years there was a significant increase in height velocity SDS in children treated with rhGH as compared to untreated children . Mean height velocity SDS after the first year of treatment was -1.2 in the control group , 2.8 in group 0.1 IU and 5.5 in group 0.2 IU . Corresponding values during the second year were -0.9 , 1.6 and 2.9 . A statistically significant difference was observed between the groups receiving 0.1 IU/kg/day and 0.2 IU/kg/day during the first year of treatment , whereas no difference between the treatment groups was found during the second year . Catch-up growth , i.e. a height velocity 1 SD above the mean , was achieved for 86 % of group 0.1 IU and 95 % of group 0.2 IU during the first year of treatment and was maintained for 65 % and 79 % of the patients in group 0.1 IU and 0.2 IU respectively in the second year . GH treatment was associated with a distinct acceleration of bone age . Tolerance of treatment was good . No clear trends were seen in any of the laboratory variables . In conclusion , this study shows that daily rhGH given at a dose of 0.1 - 0.2 IU/kg/day for 24 months is an effective and safe therapy to increase linear growth and induce catch-up growth in short SGA children 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 , BACKGROUND Turner syndrome accounts for 15–20 % of childhood usage of growth hormone ( GH ) in the UK but final height benefit remains uncertain . The most effective strategy for oestrogen replacement is also unclear . METHODS Fifty eight girls who , at start of treatment , were of mean age 9.1 years and projected final height 142.2 cm were r and omised to receive in year 1 , either low dose ethinyloestradiol 50–75 ng/kg/day , GH 28 IU/m2 surface area/week as a daily injection , or a combination of ethinyloestradiol and GH . After the first year , the ethinyloestradiol treated girls received combination treatment . After two years , girls aged over 12 years were given escalating ethinyloestradiol to promote pubertal development . RESULTS  Near final height was available for 49 girls at age 16.5 years , 146.8 cm , representing a gain of 4.6 cm , range −7.9 to + 11.7 cm . Twelve of the 49 girls gaining 7.5 cm or more were less than 13 years at the start and had received GH for at least four years . Height gain was correlated with greater initial height deficit . Fifteen girls ( 31 % ) reached 150 cm or more compared to a predicted 10 % . Early supplementation with ethinyloestradiol  provided no final height advantage . CONCLUSIONS Final height gain was modest at 4.6 cm . Younger , shorter girls gained greatest height advantage from GH . Low dosage ethinyloestradiol before planned induction of puberty was not beneficial OBJECTIVE AND DESIGN Children born small for gestational age ( SGA ) are not only at risk for short stature , but also for neurodevelopmental and behavioral problems . In this study , we analyzed the effects of high-dose GH therapy on cognitive development and psychosocial functioning in 34 prepubertal ( 3 - 8 years ) short SGA children , equally r and omized into a GH-treated group ( TRG ) and an untreated group ( UTRG ) . METHODS At start and after 2 years , children underwent st and ardized tests measuring the intellectual abilities ( Wechsler Preschool and Primary Scale of Intelligence-Revised , or Wechsler Intelligence Scale for Children-Revised ) ; their parents completed a st and ardized question naire evaluating psychosocial functioning ( Child Behavior Checklist ; CBCL ) . RESULTS At start , total IQ scores were significantly ( P < 0.05 ) lower in the SGA group than in the general population : 32 % of the SGA patients had scores below 85 . After 2 years , IQ scores remained unchanged in the TRG , but increased significantly ( P < 0.05 ) in the UTRG . After exclusion of children with developmental problems , however , no significant changes in IQ scores occurred in the UTRG as well as the TRG . At baseline , 24 % ( 8/34 ) children had problematic CBCL total problems scores , equally distributed among the two groups ; no significant changes in the different subscale scores occurred after 2 years . CONCLUSION No beneficial effect of 2 years of GH therapy on cognitive and behavioral profile could be observed in a cohort of rather young short SGA children presenting a variable degree of developmental delay and behavioral problems . Subsequent follow-up could reveal potential long-term effects of GH therapy on development and behavior 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 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 OBJECTIVE In order to ascertain the advantages of early GH treatment in Turner syndrome ( TS ) , we started a prospect i ve study aim ed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose ( 1.0 IU/kg per week ) since they were less than 6 years old and for at least 5 years before entering puberty . PATIENTS AND DESIGN Following a minimum of 6 months of baseline observations , 29 girls with TS were enrolled for this prospect i ve study provided that they ( a ) were less than 6 years old , ( b ) were below -1.0 st and ard deviation score ( SDS ) for height , ( c ) had a projected adult height ( PAH ) lower than the respective target height ( TH ) and ( d ) had a height velocity ( HV ) lower than -1.0 SDS . All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height , HV and PAH . RESULTS After a dramatic acceleration during the 1st year , HV was attenuated during the subsequent years , reaching its nadir at the 5th year . Height deficiency under therapy progressively decreased from entry onwards , shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS . In the same period , mean PAH progressively increased , although after 5 years it remained lower than the average TH . CONCLUSIONS ( a ) An effective growth-promoting strategy in TS should be based on early GH treatment , as suggested by our results . ( b ) This strategy could result in a prepubertal normalization of height , thus allowing the appropriate timing for the induction of puberty . ( c ) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy , as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment . ( d ) No acceleration of bone maturation was observed under this treatment regimen 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 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 The effect of growth hormone ( GH ) therapy on renal function was investigated in 203 children who had undergone kidney transplantation . In addition , the efficacy of GH in stimulating growth as well as other aspects of safety were assessed . The patients were r and omized to receive either GH , 1 IU/kg/week , administered subcutaneously once daily , or no treatment during the first year ( controls ) . During the second year , all patients received GH . The change in growth velocity and A height SD score during the first year of GH treatment was statistically significant compared with controls ( p < 0.0001 ) . During the second year , those patients who received GH during the first year continued to show an increased rate of growth compared with that during the pretreatment period ; however , the mean growth rate was lower than that in the first year of treatment . The mean change in glomerular filtration rate did not differ between the treated and control groups during the first year of the study . However , acute rejection episodes tended to be more frequent during GH treatment , particularly in those patients who had a history of more than one episode . Close monitoring of renal function is therefore recommended OBJECTIVE To determine whether there is evidence for impaired testicular function at final height in short boys treated with growth hormone ( GH ) during their childhood and adolescence . STUDY DESIGN The analysis was restricted to males who had isolated GH deficiency or idiopathic short stature , and who were included in the Swedish National Registry and the Swedish GH trials . The subjects had to have been treated with GH for at least 4 years ; the treatment had to have been started prepubertally , given for at least one year before the onset of puberty and the subjects had to have reached final height . One hundred and eleven boys fulfilled the criteria . METHODS Testicular volumes were determined by  orchidometer  in each boy when GH treatment was started and at final height . Sample s for testosterone measurements were collected from 77 boys at final height , and were measured by RIA . RESULTS Each subject had normal testicular size ( 15 ml or more ) and for those in whom concentrations were determined , serum testosterone levels and diurnal rhythm were normal . CONCLUSIONS The results of our survey do not show evidence of testicular impairment following GH therapy BACKGROUND Severe GH deficiency ( GHD ) is associated with , increased cardiovascular risk and intima-media thickness ( IMT ) at major arteries . OBJECTIVE The objective of the study was to investigate the 5-yr effects of GH replacement on common carotid IMT and insulin resistance syndrome ( IRS ) ( at least two of the following : triglycerides levels > or = 1.7 mmol/liter , high-density lipoprotein-cholesterol levels < or = 1.0 mmol/liter , blood pressure above 130/85 mm Hg , fasting glucose 6.1 - 7 or 2 hr after glucose 7.7 - 11.1 mmol/liter ) . DESIGN This was an interventional , open , prospect i ve , controlled study . PATIENTS Patients included 35 men with severe GHD and 35 age-matched healthy men as controls . INTERVENTION All patients received st and ard replacement therapy ; GH replacement was added in 22 patients ( group A ) and refused by 13 others ( group B ) . MEASUREMENTS Five-year changes in IMT and IRS prevalence were measured . RESULTS At baseline , IMT was higher in the patients with ( P < 0.001 ) and without IRS ( P = 0.004 ) than in controls . Eighteen patients ( 51.4 % ) and two controls ( 5.7 % ; P < 0.0001 ) had IRS . At study end , use of lipid-lowering drugs ( 92.3 , vs. 13.6 and 34.3 % , P < 0.0001 ) , glucose-lowering drugs ( 69.2 vs. 31.4 and 22.7 % ; P = 0.016 ) , and antihypertensive drugs ( 61.5 vs. 20.0 and 4.5 % ; P < 0.0001 ) was higher in group B patients than controls and group A patients . IGF-I levels normalized in all group A patients and remained lower than -1 sd score in 77 % of group B patients . IMT significantly decreased only in group A and significantly increased in controls and nonsignificantly in group B patients . IRS prevalence significantly reduced only in group A patients . CONCLUSIONS Severely hypopituitary GHD men have more frequently increased IMT at common carotid arteries and IRS than controls . After 5 years , only in GH replaced patients , IMT and prevalence of IRS decreased AIM To compare the growth response to growth hormone ( GH ) treatment in patients with idiopathic GH deficiency ( IGHD ) who were prepubertal with the response of those who were pubertal at the onset of GH therapy on an increased GH dose . PATIENTS AND METHODS Among the Turkish patients enrolled in the Pfizer International Growth Study ( KIGS ) data base with the diagnosis of IGHD , the growth data over 2 years of GH therapy were analyzed longitudinally of 113 ( 79 M ) prepubertal ( Group 1 ) and 44 ( 33 M ) pubertal ( Group 2 ) patients .  Pubertal signs were reported to be present initially or to have appeared within 6 months of GH therapy in Group 2 . Mean + /- SD age at onset of therapy was 8.7 + /- 3.5 and 13.5 + /- 1.8 years ; height SDS -4.2 + /- 1.4 and -3.2 + /- 1.1 ( p < 0.05 ) in Groups 1 and 2 , respectively . Mid-parental height ( MPH ) SDS did not show a significant difference between the two groups ( -1.5 + /- 1.1 vs -1.7 + /- 1.1 ) . RESULTS Delta height SDS over 2 years of therapy was significantly higher in Group 1 ( 1.1 + /- 1.0 ) than in Group 2 ( 0.7 + /- 0.6 ) ( p < 0.05 ) in spite of a significantly lower dose of GH ( 14.6 + /- 3.3 in Group 1 vs 17.0 + /- 3.1 IU/m2/week in Group 2 , p < 0.05 ) . Ht -- MPH SDS showed an increase from -2.4 + /- 1.7 to -1.4 + /- 1.5 in Group 1 and from -1.5 + /- 1.5 to -0.8 + /- 1.3 in Group 2 . Overall delta height SDS showed negative correlations with age ( r = -0.32 ) , height SDS ( r = -0.41 ) and height -- MPH SDS ( r = -0.40 ) at onset of therapy ( p < 0.001 ) . CONCLUSIONS These data show that in IGHD the slight increase ( 15 - 20 % ) in the dose of GH during puberty was not adequate to maintain height velocity at the same magnitude as in prepuberty , and thus was not cost effective BACKGROUND Prader-Willi syndrome ( PWS ) is a congenital alteration of chromosome pair 15 . It is characterized by short stature , muscular hypotonia , hyperphagia , obesity , behavioural and emotional disturbances , hypogonadism and partial Growth Hormone ( GH ) deficiency . The aim of this study was to assess the long-term effect of GH treatment on the psychological well-being and Quality of Life ( QoL ) in an adult PWS group . METHODS A total of 13 PWS patients , their diagnosis confirmed by genetic tests , and their parents were recruited for this study . The participants were administered the 36-Items Short Form Health Survey ( SF-36 ) and the Psychological General Well-Being Index ( PGWBI ) , for the assessment of QoL and psychological well-being , at the beginning of GH treatment , and at following intervals of 6 , 12 and 24 months . Modified versions of the same question naires were given to the parents . RESULTS Significant improvement with respect to the baseline was found , on both scales , in the evaluation of both physical and psychological well-being , although the parents ' evaluation was less optimistic than that of the patients . CONCLUSION Our findings suggest that the amelioration of QoL and psychological status is sustained in patients who continue GH treatment 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 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 The aim of this prospect i ve , longitudinal , controlled study is to describe the long-term safety and efficacy of growth hormone ( GH ) administration on craniofacial morphology in boys with short stature . Forty-six boys , who started GH treatment at the Department of Paediatrics Göteborg Paediatric Growth Research Centre , were consecutively included in the study . Twenty-five boys were classified as growth hormone-deficient ( GHD ) and 21 as idiopathic short stature ( ISS ) . The patients were injected with 33 ( n=31 ) or 67 ( n=15 ) microg GH/kg body weight/day . The mean age at the start of treatment was 11.8 years [ st and ard deviation ( SD ) 1.7 ] . To assess craniofacial growth , st and ard lateral cephalometric radiographs were obtained at the start of GH treatment , annually during 4 years , and at the end of GH treatment or when growth was less than 1 cm/year . The mean follow-up period was 6.4 years ( SD 1.4 ) . Growth changes were compared with boys from a semi-longitudinal reference group of 130 healthy subjects , 7 - 21 years of age . t-tests for independent and paired sample s and multiple regression analysis were applied . Age- and gender-specific st and ard deviation scores for the cephalometric variables were calculated . Repeated measures analysis of variance was used to identify significant covariates over time , such as low/high GH dose and GHD/ISS and orthodontic treatment . During the study period , eight ( out of 40 ) boys were treated with fixed orthodontic appliances , three with functional appliances ( activators ) , and three with other appliances ( plates and lingual arches ) . During GH treatment period , an overall enhancement in growth of the facial skeleton was observed in boys with short stature . The changes induced by GH yielded a more prognathic growth pattern , a more anterior position of the jaws in relation to the cranial base , and increased anterior rotation of the m and ible . The m and ibular corpus length and anterior face height of the GH-treated boys were greater at the end of the study compared with the boys in the reference group . No differences in growth response were noted either between the GHD and ISS boys or between those treated with either 33 ( low dose ) or 67 ( high dose ) microg GH/kg body weight/day . The only change that remained significantly correlated with orthodontic treatment was the alteration in m and ibular ramus height , showing a larger change in the boys who had not undergone orthodontic therapy . The findings of this study demonstrate that GH treatment has a favourable influence on the craniofacial growth pattern of boys with short stature without acromegalic features GH therapy variably reduces the height deficit of short children born small for gestational age ( SGA ) but is associated with hyperinsulinemia . Intermittent , higher-dose GH regimens may be alternatives to continuous , lower-dose treatment . We examined whether the growth response to GH therapy is related to pre-treatment indices of endogenous somatotropic activity , and studied the reversibility of the insulin resistant state induced by GH . 13 non-GH deficient short SGA children were r and omised to high-dose GH ( 100 mcg/kg/day ) by daily sc injection ( n = 9 ) , or no GH treatment ( n = 4 ) for 2 years ( 2/4 controls subsequently received GH treatment ) .  Overnight GH profiles  were performed at baseline ;  intravenous glucose tolerance tests  were performed at baseline , yearly on GH treatment , and 3 months post-GH treatment . Fasting glucose , insulin and proinsulin levels were measured , insulin sensitivity estimated using Bergman 's minimal model , and glucose tolerance calculated from rate of glucose disappearance . In all GH-treated children , gain in height SDS ( mean gain yr 1 = + 1.2 SDS ) was inversely related to baseline peak overnight GH ( r = -0.88 , n = 10 , p = 0.0008 ) , IFG-I ( r = -0.74 , n = 11 , p = 0.009 ) , and fasting insulin levels ( r = -0.71 , n = 11 , p = 0.014 ) . GH treatment increased fasting glucose ( means : baseline vs. yr 2 : 3.7 vs. 4.4 mmol/l , p = 0.005 ) , insulin ( 3.8 vs. 13.9 mU/l , p = 0.0002 ) , and proinsulin levels ( 1.7 vs. 4.5 pmol/l , p = 0.004 ) , and decreased insulin sensitivity ( 26.9 vs. 4.0 per min/mU/1 x 10(4 ) , p = 0.002 ) . Glucose tolerance initially decreased ( baseline : 2.62 min(-1 ) ; yr 1 : 2.18 , p = 0.02 ; yr 2 : 2.39 , p = 0.12 ) . However , by 3 months post-GH treatment significant improvements were seen in fasting insulin ( post-GH : 5.2 mU/1 , p = 0.0003 vs. yr 2 ) , proinsulin ( 1.7 pmol/l , p = 0.002 ) , and insulin sensitivity ( 17.6 per min/mU/1 x 10(4 ) , p = 0.0001 ) . Post-GH treatment , fasting glucose levels ( 4.1 mmol/l , p = 0.04 ) and glucose tolerance ( 2.49 min(-1 ) , p = 0.4 ) were similar to baseline , and the slight increase in fasting insulin levels ( 5.2 mU/1 , p = 0.04 ) was similar to that observed in non-GH treated children over the 2 yr study period ( baseline vs. 2 years : 3.9 vs. 5.9 mU/1 , n = 4 ) . In conclusion , in this study of 13 short non-GH-deficient SGA children , high-dose GH therapy induced growth responses that were associated with reversible decreases in insulin sensitivity , and that were predicted by pretreatment markers of endogenous , but not stimulated , somatotropic activity Background : The aim of this retrospective analysis was to evaluate the effects of growth hormone ( GH ) treatment on testicular development in boys with idiopathic short stature ( ISS ) and isolated GH deficiency ( IGHD ) followed in the KIGS ( Pharmacia International Growth Data base ) . Methods : For inclusion in the study , the patients had to have received more than 1 year of prepubertal GH treatment , at least 4 consecutive years of GH treatment in total , and to have attained their final height , defined as a height velocity of less than 2 cm/year . Data on 107 boys in the KIGS data base have been analyzed . Results : No significant differences in duration of GH treatment and testicular volume at the start of treatment or at final height were found between the boys with ISS and those with IGHD . The progression of testicular volume in boys with ISS or IGHD during GH treatment did not differ from the reference population . Conclusions : This analysis shows that GH treatment does not alter testicular growth in boys with ISS or IGHD . However , prospect i ve controlled studies are needed to rule out moderate attenuating or stimulating effects
target: This SR highlights the lack of long-term RCTs reporting final height data and other important qualitative outcomes , such as quality of life .
background: 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 .