TNF-alpha levels in children with growth hormone deficiency and the effect of long-term growth hormone replacement therapy. Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly Increased lipid peroxidation in adult GH-deficient patients: Effects of short-term GH administration Efficacy and safety of a new ready-to-use recombinant human growth hormone solution Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies Baseline characteristics and effects of growth hormone therapy over two years in younger and elderly adults with adult onset GH deficiency. A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients. Long-term monitoring of insulin sensitivity in growth hormone-deficient adults on substitutive recombinant human growth hormone therapy. Effects of GH on cognitive function in elderly patients with adult-onset GH deficiency: a placebo-controlled 12-month study. Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function. Diagnostic strategy for growth hormone deficiency: relevance of IGF-1 determination as a screening test. Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement. A low starting dose of genotropin in growth hormone-deficient adults. The effects of five‐year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. Long‐term cardiovascular effects of growth hormone treatment in GH‐deficient adults Preliminary data in a small group of patients Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency Long-Acting C-Terminal Peptide–Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency. Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people. Adolescents with partial growth hormone (GH) deficiency develop alterations of body composition after GH discontinuation and require follow-up.
OBJECTIVE Growth hormone ( GH ) has been suggested to modulate the release of some cytokines including TNF-alpha . To investigate TNF-alpha levels in children with GH deficiency ( GHD ) , to evaluate alteration in TNF-alpha levels during recombinant human GH ( rhGH ) treatment , and to analyze possible correlations between TNF-alpha and GH , IGF-1 and IGFBP-3 . DESIGN Twenty-four children , aged 12.60+/-2.27 years , with isolated GHD and given rhGH therapy , as subcutaneous ingestion of 0.03 - 0.04mg/kg once-daily dose , were evaluated . Eleven had complete and 13 had partial GHD . Thirty-three healthy children were studied as controls . Age and sex distribution , body mass indexes of two groups were similar . In children with GHD , blood sample s were drawn before ( TNF-alpha0 ) , and at 6 ( TNF-alpha6 ) and 12 ( TNF-alpha12 ) months of the treatment with rhGH .  TNF-alpha was determined using a human TNF-alpha ELISA assay ( Bio source International ) . RESULTS TNF-alpha0 levels were significantly higher in children with GHD than in controls ( 41.79+/-25.04 and 8.63+/-4.48pg/ml , respectively , p<0.001 ) and decreased significantly during rhGH treatment ( TNF-alpha0=41.79+/-25.04 , TNF-alpha6=13.67+/-9.95 , TNF-alpha12=10.86+/-6.61pg/ml , p<0.05 ) . There was no correlation between TNF-alpha levels and BMI , IGF-1/logIGF1 , IGFBP-3 levels and growth velocity of the patients with GHD . Although no correlation between TNF-alpha and peak GH levels after stimulation was present ; a moderate reverse correlation between TNF-alpha and basal serum concentrations of GH ( r=-0.512 , p=0.046 ) was demonstrated . CONCLUSIONS TNF-alpha levels are significantly higher in children with GHD than the controls , and long-term therapy with rhGH effectively reduces its level . Our data suggest that GH plays an inhibitory role on TNF-alpha release in humans . However , due to inconsistent results up to now , further prospect i ve , controlled and long term studies are needed to eluci date the issue The aim of this study was to assess the effects of replacement with recombinant human growth hormone ( rhGH ) in patients with GH deficiency ( GHD ) after treatment of acromegaly . Intervention study . Sixteen patients ( 8 men , age 56 years ) , treated for acromegaly by surgery and radiotherapy , with an insufficient GH response to insulin-induced hypoglycaemia , were treated with 1 year of rhGH replacement . Study parameters were assessed at baseline and after 1 year of rhGH replacement . Study parameters were cardiac function , body composition , bone mineral density ( BMD ) , fasting lipids , glucose , bone turnover markers , and Quality of Life ( QoL ) . During rhGH replacement  IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD ( P = 0.001 ) , with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women . Nonetheless , rhGH replacement  did not alter cardiac function , lipid and glucose concentrations , body composition or QoL. Bone turnover markers ( PINP and β crosslaps ) levels increased ( P = 0.005 and P = 0.021 , respectively ) , paralleled by a small , but significant decrease in BMD of the hip . The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study Objective : Adult GH deficiency ( GHD ) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality . Oxidative stress appears to play an important role in early atherogenesis . Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium . Its concentrations are increased in GHD , but the association between this abnormality and oxidative stress is still unclear , due to the discordant results yielded by the few available studies . Design and methods : In 13 GHD patients , plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH ( rhGH ) and compared with those of 13 age- and sex-matched controls . In the same subjects , the so-called “ lag-time ” , an index of anti-oxidant activity and thus of plasma oxidative balance , was also measured using a fluorescence kinetics method . Results : Before treatment , peroxide levels were significantly higher in patients than in controls ( 374.0±31.52 vs 268.0±8.51 U.C. , p<0.01 ) , whereas the lag-time was significantly lower ( 113.0±10.70 vs 168.0±7.80 min , p<0.01 ) . RhGH administration to patients result ed both in a significant decrease in lipid peroxide levels ( from 374.0±31.52 to 336.0±33.17 U.C. , p<0.01 ) and a significant prolongation of lag-time ( from 113.0±10.70 to 144.0±15.00 min , p<0.01 ) . After treatment , both parameters were no longer significantly different in patients and controls . Lagtime and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients . After replacement therapy , however , lag-time was positively ( r2= 0.62 , p<0.01 ) , and peroxide levels negatively ( r2=0.41 , p<0.05 ) , correlated with IGF-I levels . Conclusions : These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former . This abnormality , likely contributing to the increased atherogenic risk of GHD patients , is corrected by short-term GH administration at a dose able to increase , although not to fully normalize , IGF-I levels 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 Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone ( PEG-rhGH ) ( Jintrolong ) vs daily rhGH for children with growth hormone deficiency ( GHD ) . Design Phase II and III , multicenter , open-label , r and omized controlled trials . Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively . Patients in the phase II study were r and omized 1:1:1 to weekly Jintrolong ( 0.1 mg/kg/week PEG-rhGH complex ) , weekly Jintrolong ( 0.2 mg/kg/week PEG-rhGH complex ) or daily rhGH ( 0.25 mg/kg/week ) for 25 weeks . Patients in the phase III study were r and omized in a 2:1 ratio to weekly Jintrolong ( 0.2 mg/kg/week ) or daily rhGH ( 0.25 mg/kg/week ) for 25 weeks . The primary endpoint for both studies was height velocity ( HV ) increase at the end of treatment . Other growth-related parameters , safety and compliance were also monitored . Results The phase II study established the preliminary efficacy , safety and recommended dose of Jintrolong PEG-rhGH . In the phase III study , we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment ( from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year ) vs daily rhGH ( from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year ) at the end of treatment ( P < 0.05 ) . Additionally , significantly greater improvement in the height st and ard deviation scores was associated with Jintrolong throughout the treatment ( P < 0.05 ) . Adverse event rates and treatment compliance were comparable between the two groups . Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH CONTEXT The effects of GH replacement in elderly GH-deficient ( GHD ) adults are not well known . OBJECTIVE / DESIGN / PATIENTS In this prospect i ve , single-center , open-label study , baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients ( mean age , 37 yr ; range , 27 - 46 yr ) . All patients had adult onset disease , and both groups were comparable in terms of the number of pituitary hormonal deficiencies , gender , body mass index , and waist/hip ratio . Duration of hypopituitarism was , however , longer in the elderly patients . RESULTS The mean maintenance dose of GH was 0.31 ( sem , 0.03 ) mg/d in the elderly GHD patients and 0.44 ( 0.04 ) mg/d in the younger patients . The less marked response in IGF-I sd score , total body fat , and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses . Despite the lower dose in the elderly GHD group , these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level , and these differences remained also after correction for duration of hypopituitarism . There was no difference at baseline or in responsiveness in lean mass , bone mineral density , and glucose homeostasis . CONCLUSIONS This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism .  GH replacement should therefore be considered in elderly GHD adults High-dose recombinant human GH ( rhGH ) has been shown to improve the nutritional status of malnourished older adults . It is uncertain whether low-dose rhGH is effective and whether its effect on nutritional status will lead to any improvement in physical function . There is also no data on the outcome after a short course of rhGH treatment . The objectives of this study were to determine the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly patients , its effect on physical functions , and the intermediate term outcome after a 4-week rhGH treatment . The study design was a r and omized , placebo-controlled , double-blind trial conducted in a university teaching hospital . The patients were 19 medically stable malnourished elderly subjects . Intervention in the rhGH group was as follows : rhGH ( Saizen , Serono , Switzerl and ) 0.09 IU/kg body weight ( BW ) 3 times weekly were given together with appropriate dietary intervention as prescribed by the dietitian . In the placebo group , equal volumes of normal saline per kilogram BW were given 3 times weekly together with the dietary intervention . The baseline demographic , anthropometric , nutritional , and hematological variables , measures of physical function , and insulin-like growth factor I levels in both groups were comparable . Compared with the placebo group , the GH-treated group showed a more rapid gain in BW ( after 3 weeks , + 1.27 + /- 0.36 vs. -0.28 + /- 0.37 kg ; P = 0.008 ) , total lean body mass ( change after 3 weeks by bio-impedance analysis , + 1.45 + /- 0.36 vs. -0.37 + /- 0.48 kg ; P = 0.009 ) and a faster improvement in 5-m walking time ( decrease after 4 weeks , 23.79 + /- 9.41 vs. 0.45 + /- 4.62 sec ; P = 0.047 ) . The hemoglobin level rose more in the rhGH than the placebo groups ( change at 8 weeks , + 0.84 + /- 0.34 vs. -0.42 + /- 0.29 g/dL ; P = 0.012 ) . Serum albumin level also showed a greater delayed increase in the rhGH group than in the placebo group ( change at 8 weeks , + 5.1 + /- 0.8 vs. 1.6 + /- 1.2 g/dL ; P = 0.023 ) . There was no statistically significant difference for other nutritional variables . There was a greater rise in the mean serum insulin-like growth factor I level at 4 weeks in the GH than in the placebo groups ( 197 + /- 58 vs. 54 + /- 26 U/L ; P = 0.034 ) . The improvement in the rhGH group gradually diminished on follow-up and became statistically insignificant 8 weeks after stopping rhGH treatment . There were no GH-related adverse effects . Low-dose rhGH was an effective and safe adjuvant to dietary augmentation for stable malnourished elderly subjects . It led to a faster gain in total lean body mass , which was associated with greater improvement in walking speed when compared with dietary intervention alone . There were no apparent side effects Since the effects of recombinant human growth hormone ( rhGH ) replacement therapy on glucose metabolism are still a matter of debate , the aim of the present study was to evaluate the impact of long-term rhGH treatment on insulin sensitivity . Simple indices of insulin resistance ( IR ) and insulin sensitivity ( IS ) , based on fasting glucose and insulin , such as the homeostasis model assessment of insulin resistance ( HOMA-IR ) and the quantitative insulin check index ( QUICKI ) , were used to estimate the degree of IR and IS in 20 normoglycemic patients ( 11 men and 9 women ; mean age , 44 + /- 14 years ) with severe adult-onset GH deficiency ( GHD ) . Measurements were determined at baseline and after 1 and 5 years of continuous rhGH therapy . Basal values were compared to those obtained in 20 healthy sex- and age-matched controls . Starting rhGH dose ranged from 3 to 8 microg/kg/d in keeping with sex and age , then doses were titrated according to insulin-like growth factor-I ( IGF-I ) levels . At baseline all patients had low IGF-I levels ( 10 + /- 5.4 nmol/L ) , high body mas index ( BMI ; 27.5 + /- 4 kg/m(2 ) ) , and elevated body fat percentage ( BF% ; 31.8 + /- 9.6 ) . Fasting glucose and insulin levels , as well as HOMA-IR and QUICKI , did not differ significantly from those recorded in the control group . After 1 year of rhGH replacement therapy , normalization in IGF-I levels and a significant reduction in BF% were observed ( P < .001 ) , and these effects were maintained after 5 years of treatment . Fasting glucose increased from 79 + /- 10 to 87 + /- 13 , and 87 + /- 12 mg/dL ( P < .05 ) after 1 and 5 years of therapy , respectively . Fasting insulin significantly increased after 1 year , without further modifications in the long-term follow-up . HOMA-IR significantly increased from 2.1 + /- 1.7 to 2.5 + /- 1.7 ( P < .05 ) after 1 year , then decreased to 2.3 + /- 1.5 ( P = not significant [ NS ] v basal ) after 5 years . A specular decrease in QUICKI from 0.37 + /- 0.05 to 0.34 + /- 0.03 ( P < .01 ) occurred after 1 year , with a trend to increase ( 0.35 + /- 0.04 ; P = NS v basal ) after 5 years . No patient developed impaired fasting glucose . In conclusion , rhGH therapy determined an increase in fasting glucose and insulin levels , causing in the short-term period a worsening of IS . The sustained reduction in BF% , without further deterioration of IS , suggests that long-term beneficial effects on body composition may overcome the negative influence of GH on glucose metabolism OBJECTIVE Young adults with childhood-onset GH deficiency ( GHD ) have reduced memory and attention , which can be improved by treatment with GH . Little information is available on cognitive function in elderly GHD patients . DESIGN Single center , double-blind , r and omized , placebo-controlled study of 52-week duration . METHODS Elderly GH therapy naïve GHD patients ( n=34 ; age range 60 - 77 years ) were enrolled and r and omized to receive placebo or GH therapy which was titrated to achieve a target IGF-I level of + 1 to + 2 s.d . of the normal mean for age . Cognitive function was assessed at baseline and after 24 and 52 weeks , using a computerized psychometric test package ( Neurobehavioral Examination System-2 ) . RESULTS The mean GH dose was 0.16+/-0.06 mg/day ; mean IGF-I increased from 135+/-59 ng/ml at baseline to 213+/-77 ng/ml during active treatment . The GH-treated group had better mean serial digit learning scores compared with placebo group ( P<0.05 ) . Assessment of effect sizes showed that improvements in memory occurred with GH after 24 weeks . The overall adverse event rates were similar in the GH and the placebo group . CONCLUSION This study indicates that GH replacement may be accompanied by improvement in certain measures of cognitive function in elderly patients with GHD CONTEXT Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient ( GHD ) adults are limited . OBJECTIVES The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults . DESIGN The study was a 6-month double-blind , placebo-controlled r and omized trial . SETTING The study was conducted at the General Clinical Research Center . PARTICIPANTS Thirty hypopituitary adults with GHD were studied . INTERVENTION Subjects were r and omized to recombinant human GH or placebo for 6 months , followed by open-label recombinant human GH for 12 months . MAIN OUTCOME MEASURES Primary endpoints were exercise duration , maximal oxygen consumption , and left ventricular ejection fraction . Secondary endpoints were echocardiographic indices of systolic and diastolic function , left ventricular mass , lipids , and body composition . RESULTS In the 6-month double-blind phase , mean GH dose was 0.64 mg/d . Mean IGF-I sd score increased from -4.5 to -1.0 . Exercise duration , maximal oxygen consumption , left ventricular ejection fraction , and other echocardiographic parameters were normal at baseline and did not change . GH decreased total and low-density lipoprotein cholesterol by 7.5 % ( P = 0.016 ) and 14.7 % ( P = 0.002 ) ( P = 0.04 vs. placebo ) . Mean lean body mass increased by 2.2 kg ( P = 0.004 ) , fat mass decreased by 1.7 kg ( P = 0.21 ) , and percent body fat decreased by 2.5 % ( P = 0.018 ) , although between-group changes were not significant . CONCLUSIONS Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol , increased IGF-I , and increased lean body mass . These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment BACKGROUND Adult growth hormone ( GH ) deficiency must be diagnosed before prescribing therapeutic recombinant human GH . We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency ( GHD ) using IGF-1 determination as a first step . METHODS In 2000 and 2001 , we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test ( ITT ) , the reference test for the diagnosis of GHD , with concomitant Insulin-like growth factor-1 ( IGF-1 ) determination , a marker of somatotropic function . Patients were classified as GHD ( peak GH concentration<3 ng/ml with the ITT ) or normal . SETTING Monocenter prospect i ve study in a tertiary referral center . RESULTS  GHD was diagnosed in 61 subjects . Using a ROC curve , a threshold IGF-1 concentration of 175 ng/ml yielded a negative predictive value of 89+/-5 % . A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients , avoided 46/142 ITT and reduced the cost of diagnosis by 15 % . CONCLUSION We propose the use of a strategy consisting of IGF-1 determination followed , if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults CONTEXT Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency ( GHD ) . OBJECTIVE , DESIGN , AND PATIENTS : In this prospect i ve open-labeled study , the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults ( mean age of 65.2 years ; range 61 - 74 years ) .  Muscle strength was compared with reference values obtained from the background population . RESULTS The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day . The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end . GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength . Isometric knee extensor strength was reduced after 10 years . However , after correction for age and gender , using observed/predicted value ratios , there was sustained and even progressive increase in most variables reflecting muscle strength . Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years . CONCLUSIONS Ten years of GH replacement therapy in elderly GHD adults result ed in a transient increase in isometric knee flexor strength , and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function We investigated the effect of 12 weeks of recombinant human GH therapy given in three different doses on serum insulin-like growth factor I ( IGF-I ) and IGF-binding protein-3 ( IGFBP-3 ) in patients with GH deficiency ( GHD ) . We used low doses of recombinant human GH ( Genotropin ) , as we and others recently found a strong decrease in physiological GH production with age in healthy controls , especially in those older than 30 yr . Sixty patients with GHD ( aged 20 - 70 yr ) were r and omized to one of the three dose groups . Group 1 used a dose of 0.6 IU/day for 12 weeks . Group 2 started at a dose of 0.6 IU for 4 weeks followed by 1.2 IU/day for 8 weeks . Group 3 used 0.6 IU for 4 weeks , followed by 1.2 IU/day for 4 weeks and 1.8 IU/day thereafter . IGF-I concentrations ( nanomoles per L ) were determined by RIA after extraction and purification on ODS-silica columns . The measurement of IGFBP-3 ( milligrams per L ) was performed by RIA . The three groups were equal with regard to age , sex and body mass index . At the start of the study , we found lower levels of both serum IGF-I and IGFBP-3 in childhood-onset GHD than in adult-onset GHD . Moreover , there was a gender difference ; female GHD patients had lower serum IGF-I levels than male patients .  Serum IGF-I levels were low in both childhood-onset and adult-onset GHD . Serum IGFBP-3 levels , however , were low in patients with childhood-onset GHD , but normal in patients with adult-onset GHD . After 12 weeks of treatment , IGF-I levels were low normal in the low dose group and normal in groups 2 and 3 of both adult-onset and childhood-onset GHD . In adult-onset GHD , serum IGFBP-3 increased to high normal levels in all groups , whereas it increased to low normal levels in childhood-onset GHD . This study demonstrates differences in the biochemical characteristics of childhood-onset and adult-onset GHD . In patients with adult-onset GHD , serum IGFBP-3 levels are not significantly decreased and , therefore , can not be used as a screening method for GHD or as a dose-finding parameter . GH therapy at doses of 0.6 and 1.2 IU/day in male and female patients , respectively , is , in general , able to increase serum IGF-I into the normal range after 12 weeks of treatment , without reaching supranormal levels of serum IGF-I. This dose could , therefore , be a starting dose in GH-deficient adults Objective Little is known of the long‐term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency ( GHD ) . In this study , the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD CONTEXT Declines in GH and testosterone ( Te ) secretion may contribute to the detrimental aging changes of elderly men . OBJECTIVE To assess the effects of near-physiological GH with/without Te administration on lean body mass , total body fat , midthigh muscle cross-section area , muscle strength , aerobic capacity , condition-specific quality of life ( Age-Related Hormone Deficiency-Dependent Quality of Life question naire ) , and generic health status ( 36-Item Short-Form Health Survey ) of older men . DESIGN , SETTING S , AND PARTICIPANTS A 6-month , r and omized , double-blind , placebo-controlled trial was performed on 80 healthy , community-dwelling , older men ( age , 65 - 80 yr ) . INTERVENTIONS Participants were r and omized to receive 1 ) placebo GH or placebo Te , 2 ) recombinant human GH ( rhGH ) and placebo Te ( GH ) , 3 ) Te and placebo rhGH ( Te ) , or 4 ) rhGH and Te ( GHTe ) . GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range . A fixed dose of Te ( 5 mg ) was given by transdermal patches . RESULTS Lean body mass increased with GHTe ( P = 0.008 ) and GH ( P = 0.004 ) , compared with placebo . Total body fat decreased with GHTe only ( P = 0.02 ) . Midthigh muscle ( P = 0.006 ) and aerobic capacity ( P < 0.001 ) increased only after GHTe . Muscle strength changes were variable ; one of six measures significantly increased with GHTe . Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life question naire score ( P = 0.007 ) in the GH and GHTe groups . Bodily pain increased with GH alone , as determined by the Short-Form Health Survey ( P = 0.003 ) . There were no major adverse effects . CONCLUSION Coadministration of low dose GH with Te result ed in beneficial changes being observed more often than with either GH or Te alone OBJECTIVE The long‐term cardiovascular effects of GH administration in adults are of major clinical importance , given the increasing use of such treatment . We have evaluated long‐term cardiovascular effects of recombinant human GH ( rhGH ) substitution in GH deficient men Objectives Exercise is a potent physiological stimulus of GH secretion . We hypothesized that exogenous recombinant human growth hormone ( rhGH ) administration through an increase in GH and IGF‐I levels would blunt the GH response to exercise . The aim of the study was to examine and compare the impact of rhGH on the exercise‐induced GH response in healthy normal men and women 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 Context Daily injections are required for growth hormone ( GH ) replacement therapy , which may cause low compliance as a result of inconvenience and distress in patients . Objective C-terminal peptide-modified human GH ( MOD-4023 ) is developed for once-a-week dosing regimen in GH-deficient ( GHD ) adults and children . The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children . Design A multicenter , open-label , r and omized , controlled phase 2 study in children with GHD , evaluating the safety , tolerability , pharmacokinetics/pharmacodynamics , and efficacy of three different weekly MOD-4023 doses , compared with daily recombinant human GH ( r-hGH ) . Setting The trial was conducted in 14 endocrinology centers in Europe . Patients Fifty-three prepubertal children with GHD completed 12 months of treatment with either MOD-4023 ( N = 42 ) or r-hGH ( N = 11 ) . Interventions C-terminal peptide-modified hGH ( MOD-4023 ) was administered weekly at a dose of either 0.25 , 0.48 , or 0.66 mg/kg/wk and compared with daily hGH at a dose of 0.24 mg/kg/wk . Results MOD-4023 showed an estimated half-life approximately fivefold to 10-fold longer when compared with daily r-hGH . Insulin-like growth factor (IGF)-I and IGF-binding peptide 3 showed a dose-dependent increase during MOD-4023 treatment . IGF-I st and ard deviation score for MOD-4023 did not exceed + 2 . All MOD-4023 cohorts demonstrated adequate catch-up growth . The 0.66 mg/kg/wk dose demonstrated efficacy closest to daily r-hGH . No serious adverse events were observed during MOD-4023 treatment , and its tolerability was consistent with known properties of r-hGH . Conclusions This study confirms the long-acting properties of MOD-4023 and shows a promising safety and tolerability profile . This provides support for initiation of a phase 3 study in GHD children using a single weekly injection of MOD-4023 GH is being used by elite athletes to enhance sporting performance . To examine the hypothesis that exogenous 22-kDa recombinant human GH ( rhGH ) administration could be detected through suppression of non-22-kDa isoforms of GH , we studied seventeen aerobically trained males ( age , 26.9 + /- 1.5 yr ) r and omized to rhGH or placebo treatment ( 0.15 IU/kg/day for 1 week ) . Subjects were studied at rest and in response to exercise ( cycle-ergometry at 65 % of maximal work capacity for 20 min ) . Serum was assayed for total GH ( Pharmacia IRMA and pituitary GH ) , 22-kDa GH ( 2 different 2-site monoclonal immunoassays ) , non-22-kDa GH ( 22-kDa GH-exclusion assay ) , 20-kDa GH , and immunofunctional GH . In the study , 3 h after the last dose of rhGH , total and 22-kDa GH concentrations were elevated , reflecting exogenous 22-kDa GH . Non-22-kDa and 20-kDa GH levels were suppressed . Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups . In identical exercise studies repeated between 24 and 96 h after cessation of treatment , the magnitude of the responses of all GH isoforms was suppressed ( P < 0.01 ) , but the relative proportions were similar to those before treatment . We conclude : 1 ) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days ; 2 ) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations ; and 3 ) these methods may prove useful in detecting rhGH abuse in athletes We recently observed that among patients with GH deficiency due to adult-onset hypopituitarism , men responded with a greater increase in serum levels of insulin-like growth factor I ( IGF-I ) and biochemical markers of bone metabolism than women when the same dose of recombinant human GH ( rhGH ) per body surface area was administered for 9 months . In the present study , 33 of the 36 patients in the previous trial ( 20 men and 13 women ) continued therapy for up to 45 months . The dose of rhGH was adjusted according to side-effects and to maintain serum IGF-I within the physiological range . This result ed in a significant dose reduction in the men ; consequently , the women received twice as much rhGH as the men ( mean + /- SD , 1.9 + /- 1.1 vs. 1.0 + /- 0.6 U/day ; P < 0.01 ) . The increases in serum IGF-I levels and serum biochemical markers of bone metabolism were similar in men and women with these doses . The total bone mineral content ( BMC ) was increased after 33 and 45 months of treatment up to 5.1 % ( P = 0.004 and 0.0001 ) . Bone mineral density ( BMD ) , BMC , and the area of the femoral neck and the lumbar spine were also significantly increased after 33 and 45 months of treatment . When analyzed by gender , total body BMC , femoral neck BMD and BMC , and spinal BMC were significantly increased in males , but not in females ( P < 0.05 - 0.01 ) . In conclusion , rhGH treatment continued to have an effect on bone metabolism and bone mass for up to 45 months of therapy . The changes in bone mass were greater in the men , although they received lower doses of rhGH than the women . The results indicate that the sensitivity to GH in adult patients with GH deficiency is gender dependent OBJECTIVE Reduced muscle mass and strength are characteristic findings of growth hormone deficiency ( GHD ) and aging . We evaluated measures of muscle strength , muscle fiber type , and cross sectional area in response to treatment with recombinant human growth hormone ( rhGH ) with or without a structured resistance exercise program in frail older subjects . DESIGN Placebo-controlled , r and omized , double blind trial . SETTING Outpatient clinical research center at an urban university-affiliated teaching hospital . PARTICIPANTS Thirty-one consenting older subjects ( mean age 71.3 + /- 4.5 years ) recruited as a subset of a larger project evaluating rhGH and exercise in older people , who underwent 62 quadricep-muscle biopsies . INTERVENTION R and om assignment to a 6-month course of one of four protocol s : rhGH administered subcutaneously daily at bedtime , rhGH and a structured resistance exercise program , structured resistance exercise with placebo injections , or placebo injections only . MEASUREMENTS Muscle biopsy specimens were obtained from the vastus lateralis muscle . Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program . Serum insulin-like growth factor-I ( IGF-I ) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer . RESULTS The administration of rhGH result ed in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment . Muscle strength increased significantly in both the rhGH/exercise ( + 55.6 % , P = .0004 ) as well as the exercise alone ( + 47.8 % , P = .0005 ) groups . There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH ( P = .027 ) . CONCLUSIONS Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit . IGF-I was increased by administrating rhGH and muscle strength was increased by exercise . The administration of rhGH to frail older individuals in this study result ed in significant changes in the proportions of fiber types . Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study It is now a consensus to resume GH treatment in adolescents with severe GH deficiency ( GHD ) at retesting to prevent the occurrence of adult GHD syndrome . However , we do not have any data on the follow-up of adolescents with nonsevere GHD at completion of treatment . This report presents preliminary data from a 1-yr prospect i ve study that includes the first 91 patients retested .  Anthropometric data , IGF-I and IGF binding protein-3 levels , glycemia and insulinemia , lipid profile , and body composition using dual x-ray absorptiometry and abdominal computed tomography scan were recorded at completion of GH treatment and 1 yr later . Body composition was significantly different at both evaluations , with increased total body fat and decreased lean body mass in the partial GHD group vs. the normal group . Moreover , these alterations worsened after 1 yr without GH in the partial GHD group , whereas there were no modifications in the normal group . We did not find any metabolic alterations such as elevated triglyceride , total cholesterol , or insulin levels .  Adolescents with reconfirmed partial GHD exhibit alterations in body composition after 1 yr without GH , whereas those retested normal do not . These changes are similar to those described in severe GHD , although less marked , and justify a precise follow-up
RhGh did not consistently affect blood pressure or bone mineral density .
RhGH consistently improved quality of life ( QoL ) parameters reflected in AGHDA-scores .
Conclusion RhGH replacement in elderly subjects with GHD  decreases LDL cholesterol levels and improves QoL , but the effects on other parameters are not unequivocal .
There were no data on the efficacy and safety  of rhGH treatment in octogenarians with GHD
Context Recombinant human GH ( rhGH ) is prescribed for the treatment of adults with GH deficiency ( GHD ) .
However , conflicting data are available on the efficacy of rhGH treatment in elderly GHD patients .
Objective To assess the efficacy of rhGH treatment in elderly GHD subjects .