HGH (Somatropin)

Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort.

The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort. Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (≥ 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth. The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.

Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study.

Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). We aimed to compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. In this 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study, participants were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. A total of 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). The primary endpoint was annualized HV at month 12. HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: -0.24, 0.89). The lower bound of the 2-sided 95% CI was higher than the prespecified noninferiority margin (-1.8 cm/year), demonstrating noninferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height standard deviation score at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon: 78.9%, somatropin: 79.1%). The efficacy of once-weekly somatrogon was noninferior to once-daily somatropin, with similar safety and tolerability profiles. (ClinicalTrials.gov no. NCT02968004).

Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.

For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD. The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin. The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727). This trial took place at 73 sites across 15 countries. This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD. Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS). Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups. The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.

Human growth hormone.

Human growth hormone.

Lonapegsomatropin: Pediatric First Approval.

Lonapegsomatropin (lonapegsomatropin-tcgd; SKYTROFA®), a long-acting prodrug of somatropin (human growth hormone), is in development by Ascendis Pharma as a treatment for growth hormone deficiency in pediatric and adult patients. Lonapegsomatropin received its first approval in August 2021 in the USA for the treatment of pediatric patients at least 1 year of age (and weighing ≥ 11.5 kg) with growth failure due to inadequate secretion of endogenous growth hormone. Lonapegsomatropin is administered as a once-weekly subcutaneous injection; the sustained release of somatropin from lonapegsomatropin eliminates the need for daily somatropin injections. This article summarizes the milestones in the development of lonapegsomatropin leading to this first pediatric approval for the treatment of growth hormone deficiency.

Human growth hormone.

Human growth hormone.

The use of somatropin (recombinant growth hormone) in children of short stature.

The availability of somatropin [recombinant human growth hormone (GH)] has revolutionized the treatment of short stature resulting from GH deficiency. It is also widely used as an adjunct in the treatment of other disorders which do not fit the definition of classic GH deficiency, such as intrauterine growth restriction, Turner syndrome, healthy children with short stature and skeletal dysplasias. The widespread use and ready availability of GH treatment has prompted questions about its tolerability, rationality, and the psychological effects of long-term treatment, leading to several trials. Early treatment of GH deficiency will allow the child to reach his or her genetic potential, although there continues to be marked variability in the criteria used to diagnose the deficiency, and in the treatment schedule, especially during puberty. Treatment has also been shown to have a beneficial effect on growth in children with chronic renal failure, with no adverse effects on the renal function. There are, however, no long-term data to determine final height, or randomized controlled studies to justify routine use of GH in conditions such as intrauterine growth restriction. It remains controversial in conditions such as Turner syndrome and achondroplasia, where the response to treatment is only moderate. Healthy children with short stature have not been shown to have a psychological disadvantage, again proving difficult to justify prolonged GH treatment for idiopathic short stature. Meticulous monitoring, long-term follow-up to adult or near-adult final height, and well-defined endpoints of treatment need to be better clarified. The metabolic effects of treatment on the patient's lipid profile, bone mineral density, and muscle mass need careful documentation, especially with the high doses used in an already susceptible population such as low birthweight children and those with Turner syndrome. Lastly, the psychosocial impact of GH treatment, financial implications, and cost efficacy of treatment in an ever-increasing list of indications should be taken into consideration for rationalizing its use in future.

Using human growth hormone (somatropin).

Long-Acting Growth Hormone for Pediatric Growth Hormone Deficiency.

Long-acting growth hormone (LAGH) has the potential to improve adherence and outcomes over daily somatropin in growth hormone deficiency (GHD). Whereas daily somatropin products are molecularly identical, LAGHs are molecularly distinct; additional moieties or mechanisms that prolong LAGH action confer unique pharmacodynamic/pharmacokinetic properties that could affect efficacy and safety. Only one LAGH available in the United States and Europe (lonapegsomatropin) delivers unmodified somatropin. With no head-to-head clinical trials of LAGHs available, this systematic literature review and network meta-analysis were conducted to compare the relative efficacy and safety of LAGHs in pediatric GHD. Five trials were eligible for inclusion in a Bayesian network meta-analysis; 3 contributed to the base case network, including 3 LAGHs (lonapegsomatropin, somapacitan, and somatrogon) and daily somatropin. Treatment with lonapegsomatropin was associated with statistically significantly higher annualized height velocity and change from baseline in height SD score (SDS) at week 52 compared to daily somatropin and somapacitan; no other significant differences in these outcomes were found. The change from baseline in average insulin-like growth factor-1 (IGF-1) SDS at week 52 was significantly higher for somatrogon vs all comparators and for lonapegsomatropin vs daily somatropin and somapacitan; average IGF-1 SDS was within normal range in all trials. No significant differences were seen in progression in bone age-to-chronological age ratio or serious adverse events (SAEs). Sensitivity analyses were consistent with the base case. In this network meta-analysis, lonapegsomatropin was the only LAGH associated with better growth outcomes. No significant differences were detected regarding SAEs; other safety outcomes could not be analyzed.

Five-year safety and growth response of long-acting PEGylated recombinant human growth hormone in children with growth hormone deficiency-data from CGLS database.

Growth hormone deficiency (GHD) is an endocrine disorder characterized by insufficient production of growth hormone (GH). PEGylated recombinant human growth hormone (PEG-rhGH; Jintrolong®, GeneScience Pharmaceuticals Co., Ltd.) is the only long-acting GH approved in China for treating paediatric GHD (PGHD). Long-term Efficacy and Safety Evaluation of Growth Hormone in Children in China (CGLS) is a large, surveillance registry database of participants with short stature treated with PEG-rhGH or rhGH in a real-world setting. In this study, we evaluated the safety profile and five-year growth response of PEG-rhGH based on the data from the CGLS database in participants with PGHD in China. In this real-world registry-based observational study, a total of 1,207 participants were included in the safety analysis set. Of these, 339 participants who had received PEG-rhGH continuously for five years were also included in the efficacy analysis. Key outcomes assessed comprised adverse events (AEs), serious AEs (SAEs), and height gain. The safety assessment indicated that 563 participants exhibited 1328 AEs with an incidence rate of 46.6%. Furthermore, SAEs occurred in 1.0% of participants (n = 12), with none of them associated with PEG-rhGH treatment. A significant increase in mean change in height-SD score (∆Ht SDS) was observed during the treatment period, with a mean ∆Ht SDS of 2.1 ± 0.9 in five years. Subgroup analysis showed that the younger participants exhibited a more favourable response to therapy. CGLS data showed that five-year PEG-rhGH treatment in children with PGHD was associated with a favourable safety profile and sustained height gain. • Several long-acting growth hormones (LAGH) have been approved for use in PGHD. PEGylated recombinant growth hormone (PEG-rhGH) is the only LAGH marketed in China, with its three-year efficacy and safety have been reported. • Data from the CGLS database confirms that PEG-rhGh has an acceptable safety profile over five years, with significant improvement in height. Importantly, the data indicate that initiating the treatment earlier yields better outcomes.

Human growth hormone.

PEGylation of somatropin (recombinant human growth hormone): impact on its clearance in humans.

1. PHA-794428 is a PEGylated version of somatropin (human growth hormone). The pharmacokinetics of PHA-794428 have been studied in humans following single subcutaneous administration (dose range 10-500 microg kg(-1)). In the same study the pharmacokinetics of somatropin were also determined following a 3.6 mg (51 microg kg(-1)) subcutaneous dose. Comparison of the pharmacokinetics of both molecules indicates that PEGylation of somatropin with a 40 kD PEG results in a ten- to 20-fold increase in area under the curve and a similar increase in half-life when compared with somatropin in human (at equivalent subcutaneous doses). 2. Literature data indicate that somotropin is cleared by two mechanisms. The first processes is clearance by glomerular filtration. This is a passive, non-capacity-limited process. A second, capacity-limited, process is mediated by interaction with growth hormone receptors present in a number of tissues including the liver. It is hypothesized that PHA-794428 shares the same clearance mechanisms. However, the addition of the PEG moiety has modulated the clearance by both of these processes. Pharmacokinetic modelling of human serum concentration data obtained for these molecules strongly supports this hypothesis. The renal clearance is reduced due to the increased size of the molecule (Cl/F reduced from 9.6 to 0.1 l h(-1) for somatropin and PHA-794428, respectively). In addition, the reduction in growth hormone receptor affinity has reduced the clearance mediated by interaction with this receptor (somatropin Km = 3.6 microg l(-1) and Vmax = 104 microg h(-1)/PHA-794428 Km = 53 microg l(-1) and Vmax = 84 microg h(-1)).

Human growth hormone.

Human growth hormone.

Intestinal adaptation following resection.

Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

Evaluation of human growth hormone (somatropin) in socket healing: a split-mouth randomized controlled trial.

Techniques for preserving alveolar bone after tooth extraction are becoming a part of the usual clinical practice of clinicians. These techniques aim at minimizing postextraction bony resorption, hence, minimizing subsequent follow-up for implant insertion. This randomized clinical study aimed to measure and compare alveolar bone and soft tissue healing between extraction sockets treated with somatropin to untreated sockets. The study is designed as a split-mouth randomized clinical trial. The selected patients were indicated for bilateral symmetrical tooth extraction, where each patient had an indication to extract two symmetrical teeth in anatomy and number of roots. Somatropin was applied to the tooth socket of the randomly selected side after tooth extraction by gel foam, and the control side was filled with gel foam only. A clinical follow-up of the soft tissue was done 7 days after tooth extraction to evaluate clinical aspects of the healing process. Radiographic follow-up was performed using a cone-beam computed tomography scan to assess volumetric changes of alveolar bone in the extraction area prior to and 3 months after the surgical procedure. A total of 23 patients (aged 29.1&#xb1;9.5 years) participated. The results showed a statistically significant association between somatropin application and better preservation of the bony dimensions of the alveolar ridge. Bone loss was -0.691&#xb1;0.628&#xa0;mm for the buccal plate on the study side compared to -2.008&#xb1;1.175&#xa0;mm on the control side. The level of the lingual/palatal plate bone loss was -1.052&#xb1;0.855&#xa0;mm on the study side compared to -2.695&#xb1;1.878&#xa0;mm on the control side. The bone loss of alveolar width was -1.626&#xb1;1.061&#xa0;mm on the study side compared to -3.247&#xb1;1.543&#xa0;mm on the control side. The results also showed better healing of covering soft tissues (P<0.05), as well as bone density in the socket where somatropin was applied, which has been statistically significant. The data from this study demonstrated that the application of somatropin in tooth sockets postextraction showed an effective contribution to reducing alveolar bone resorption and improving bone density following extraction, in addition to better healing of covering soft tissue.

Transgenic Artifacts Caused by Passenger Human Growth Hormone.

The minigene encoding human growth hormone (hGH) has been incorporated into over 300 transgenic mouse lines to improve transgene expression. However, unexpected and functional hGH expression can drastically alter physiology. We list here the mouse lines in which ectopic hGH has been confirmed, and we provide a wiki for lines awaiting analysis.

Outcomes of recombinant growth hormone therapy in the traumatic brain injury population: A scoping review.

Post-traumatic hypopituitarism (PTHP), including growth hormone deficiency (GHD), is a prevalent and underdiagnosed complication of traumatic brain injury (TBI), resulting in substantial morbidity. Emerging evidence suggests that recombinant human growth hormone (rhGH) therapy may provide benefit for patients with confirmed GHD, and also those with growth hormone insufficiency (GHI), abnormal growth hormone secretion (AGHS), or Brain Injury Associated Fatigue and Altered Cognition (BIAFAC), even when peak growth hormone response to growth hormone stimulation testing is above traditional GHD diagnostic cutoffs in these patients. To conduct a scoping review evaluating the effects of rhGH in adults with TBI, including those classified as GHD, GHI, AGHS, or BIAFAC, on clinical, functional, and neurobiological outcomes. A comprehensive search of PubMed/MEDLINE was performed using a peer-reviewed search strategy. Studies were screened in duplicate. Eligible studies included clinical trials,&#xa0;observational studies, and case series, reporting rhGH use in adults with a history of TBI, with or without GHD. Outcomes included quality of life, neuropsychological performance, physical functioning, biochemical markers, and neuroimaging data. Eleven studies met inclusion criteria: two double-blind, randomized, placebo-controlled trials; one double-blind, randomized, placebo-controlled crossover study; one double-blind, non-randomized, placebo-controlled trial; two non-randomized controlled trials; three retrospective cohort studies; and two open-label, single-arm trials. Across the studies reviewed, the researchers reported improvements in insulin-like growth factor-1 (IGF-1) levels, fatigue, mood, physical performance, and cognition. Structural and functional neuroimaging changes following rhGH were also reported, including increased cortical thickness and gray matter volume, and improved functional connectivity of somatosensory networks. Symptomatic improvement as well as improvements in objective measures were described among patients who did not meet diagnostic cut-point criteria for GHD. Evidence suggests that rhGH may confer benefit in a broad range of symptomatic TBI patients, including those with peak growth hormone values in ranges overlapping with normal, healthy controls. Larger, controlled studies are warranted to validate these findings and inform clinical guidelines.

Editorial: Human growth hormone.

Recombinant growth hormone therapy for cystic fibrosis in children and young adults.

Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 11 February 2015.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 04 March 2015. Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. One study showed moderate improvement at one time point in one parameter of pulmonary function tests, forced vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment, but there was no consistent benefit in lung function across all studies. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects. Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement at a single time point, but no consistent benefit was seen across all studies. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in people with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use.

Somatropin therapy in italian adults with growth hormone deficiency.

In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions. Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces. From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21&#x2009;&#xb1;&#x2009;0.33 visits/year). The diagnoses were: hypopituitarism (n&#x2009;=&#x2009;579); hypophysectomy (n&#x2009;=&#x2009;383); and congenital GHD (n&#x2009;=&#x2009;3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (&#xb1;&#x2009;0.212) mg/day, 0.292 (&#xb1;&#x2009;0.167) mg/day in male and 0.360 (&#xb1;&#x2009;0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420&#x2009;&#xb1;&#x2009;0.225&#xa0;mg/day), with a progressive decrease of the dosage during the follow-up. This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.

Somatropin (Zorbtive): in short bowel syndrome.

A somatropin preparation (Zorbtive) produced by recombinant DNA technology has been evaluated in patients with short bowel syndrome. Somatropin is thought to enhance intestinal adaptation in this condition through direct or indirect effects on the intestine. In a randomised, double-blind study in patients with short bowel syndrome who were dependent on intravenous parenteral nutrition (IPN) [n = 41], recipients of subcutaneous somatropin alone or somatropin plus oral glutamine had significantly greater mean reductions from baseline in weekly total IPN volume than recipients of placebo plus glutamine. All patients received a special diet. In addition, significantly greater mean reductions from baseline in weekly total IPN calories and the mean frequency of IPN or supplemental lipid emulsion administration occurred in patients receiving somatropin alone or in combination with glutamine, compared with recipients of placebo plus glutamine. Adverse events were reported in 100% of patients with short bowel syndrome during treatment with somatropin with or without glutamine. However, a high proportion of patients also reported signs and symptoms before starting therapy or adverse events after therapy, suggesting that such patients experience numerous events attributable to their underlying condition or to complications of IPN.

Recombinant growth hormone for children and adolescents with Turner syndrome.

Turner syndrome (TS) affects about one in 1500 to 2500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Untreated women are approximately 20 to 21 cm shorter than normal women within their respective populations. Recombinant human growth hormone (hGH) has been used to increase growth and final height in girls who have Turner syndrome. To assess the effects of recombinant growth hormone in children and adolescents with TS. MEDLINE, EMBASE, The Cochrane Library, LILACS, BIOSIS, Science Citation Index and reference lists were used to identify relevant trials. Randomised controlled trials were included if they were carried out in children with TS before achieving final height. Growth hormone had to be administered for a minimum of six months and compared with a placebo or no treatment control condition. Two reviewers assessed studies for inclusion criteria and for methodological quality. The primary outcomes were final height and growth. Secondary outcomes included bone age, quality of life, cognitive performance, and adverse effects. Four RCTs that included 365 participants after one year of treatment were included. Only one trial reported final height in 61 treated women to be 148 cm and 141 cm in 43 untreated women (mean difference (MD) seven cm, 95% CI 6 to 8). Short-term growth velocity was greater in treated than untreated girls after one year (two trials, MD three cm per year, 95% CI 2 to 4) and after two years (one trial, MD two cm per year, 95% CI 1 to 2.3). Skeletal maturity was not accelerated by treatment with recombinant growth hormone (hGH). Adverse effects were minimally reported. Recombinant human growth hormone (hGH) doses between 0.3 to 0.375 mg/kg/wk increase short-term growth in girls with Turner syndrome by approximately three (two) cm in the first (second) year of treatment. Treatment in one trial increased final height by approximately six cm over an untreated control group. Despite this increase, the final height of treated women was still outside the normal range. Additional trials of the effects of hGH carried out with control groups until final height is achieved would allow better informed decisions about whether the benefits of hGH treatment outweigh the requirement of treatment over several years at considerable cost.

Somatropin (mammalian cell-derived recombinant human growth hormone) for HIV-associated wasting.

Improvement in body composition of Japanese participants with Prader-Willi syndrome following somatropin treatment: an open-label, multi cohort Phase 3 study.

Recombinant human growth hormone (GH; somatropin) treatment has beneficial effects on body composition in patients with Prader-Willi syndrome (PWS). However, this treatment option is limited to children in most countries and to children with short stature in countries such as the USA and Japan. The aim of this multicohort study was to evaluate the effect of somatropin on body composition and to assess its safety in Japanese pediatric and adult participants with PWS. GH-na&#xef;ve pediatric participants (n = 6) received somatropin 0.245 mg/kg/week, GH-treated pediatric participants (n = 7) received somatropin 0.084 mg/kg/week, and adult participants (n = 20) received somatropin 0.042 mg/kg/week for 1 month, followed by 0.084 mg/kg/week. The study met its primary endpoint in the adult cohort because the least squares mean (95% CI) of the change from baseline to Month 12 in lean body mass (LBM) (%) was greater than the prespecified efficacy criterion of 0. LBM (%) was higher at 12 months in GH-na&#xef;ve pediatric participants, while GH-treated pediatric participants showed little deterioration in LBM despite reduced GH dosage. Treatment-emergent adverse events (TEAEs) were experienced by five (83.3%), five (71.4%), and 19 (95.0%) participants in the GH-na&#xef;ve pediatric cohort, GH-treated pediatric cohort, and adult cohort, respectively. Most TEAEs were mild or moderate in severity. Three participants reported four serious TEAEs, and none were treatment related. Somatropin improved body composition in adult participants, enabled maintenance of body composition in pediatric participants, and demonstrated a favorable safety and tolerability profile in all PWS cohorts. (ClinicalTrials.gov ID: NCT04697381).

Lonapegsomatropin (Skytrofa) for growth hormone deficiency.

Human growth hormone and glutamine for patients with short bowel syndrome.

There has been clinical enthusiasm for treating short bowel patients with human recombinant growth hormone and/or glutamine in hopes of reducing parenteral nutrition dependency. It has been more than a decade since Byrne and colleagues reported enhanced absorption of nutrients, improved weight gain, and reduction in parenteral nutrition requirements with the administration of a combination of human growth hormone (HGH) and glutamine in patients with short bowel syndrome. Other studies have reported inconsistent results. The purpose of this systematic review was to evaluate the efficacy of growth hormone with or without glutamine supplementation for adult patients with short bowel syndrome. Electronic searches were performed to identify all publications describing randomised controlled trials of the use of human growth hormone with or without glutamine for the treatment of patients with short bowel syndrome. Randomised controlled trials of human growth hormone with or without glutamine for patients with short bowel syndrome were considered for inclusion. Two authors independently extracted data from the published studies. The statistical analyses were performed using RevMan 5 software. Follmann's method was used for cross-over studies. Five studies were included in the review. Human growth hormone with or without glutamine appears to provide benefit in terms of increased weight (MD 1.66 Kg; 95% CI 0.69 to 2.63;P = 0.0008), lean body mass (MD 1.93 Kg; 95% CI 0.97 to 2.90; P = 0.0001) energy absorption (MD 4.42 Kcal; 95% CI 0.26 to 8.58; P = 0.04) and nitrogen absorption (MD 44.85 g; 95%CI 0.20 to 9.49; P = 0.04) for patients with short bowel syndrome. The single RCT that focused on parenteral nutrition (PN) requirements demonstrated decreased PN volume and calories and number of infusions in patients who received HGH with or without glutamine supplementation. Only patients who received HGH with glutamine maintained statistically significant PN reductions at 3 month follow-up. The results suggest a positive effect of human growth hormone on weight gain and energy absorption. However, in the majority of trials, the effects are short-lived returning to baseline shortly after cessation of therapy. The temporary benefit calls into question the clinical utility of this treatment. To date, the evidence is inconclusive to recommend this therapy. Consideration should be made to studying patients during the active phase of intestinal adaptation rather than in the setting of chronic intestinal failure. The role of HGH in paediatric short bowel syndrome remains unknown.

Recombinant growth hormone therapy for cystic fibrosis in children and young adults.

Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 15 May 2013.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 15 March 2012. Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. There is moderate improvement in one parameter of pulmonary function tests, functional vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects. Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in patients with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use in patients.

[Epiphysiolysis and recombinant growth hormone].

Impaired quality of life in hypopituitary adults with growth hormone deficiency : can somatropin replacement therapy help?

It is generally known that growth hormone (GH)-deficient patients experience emotional instability, reduced energy, sleep disturbances, and problems with (sexual) relationships. GH and insulin-like growth factor-1 (IGF-I) may affect mood parameters by their actions at binding sites in specific brain areas and/or by their effects on dopamine turnover in the brain. Indeed, there is substantial evidence that somatropin (growth hormone) treatment improves the quality of life (QOL) of GH-deficient patients.However, the variety of instruments used makes it questionable whether QOL in particular is affected by somatropin therapy. The measurement of QOL is subject to methodologic difficulties and is frequently not properly distinguished from health status and well-being. QOL ratings are characterized by an emphasis on mental health and health status by an emphasis on physical function, while well-being is concerned with depression, anxiety, and energy levels. Examples of instruments used to measure QOL, health status, and well-being in GH-deficient patients are the Quality of Life-Assessment of Growth Hormone Deficiency in Adults, the Short-Form Health Survey, and the Psychological General Well-Being Schedule, respectively. One additional problem in establishing the effects of somatropin treatment on QOL is that the QOL effects of somatropin treatment may be different for patients with isolated GH deficiency (GHD) and those with multiple pituitary hormone deficiencies.Previously, in order to answer the question of whether somatropin therapy improves mood status in GH-deficient patients, we conducted a meta-analysis comparing somatropin treatment effects relative to baseline and placebo. At 3, 6, and 12 months of somatropin replacement the mood status of GH-deficient patients improved with decreasing effect sizes over time (d = 0.81, 0.55, and 0.29, respectively) from baseline. However, the median somatropin treatment period of 6 months did not improve mood status more than placebo. In a second analysis we classified the questionnaires into those on QOL, those on health status, and those on well-being, respectively, and analyzed the separate effects of pooled treatment durations of about 9 months. Somatropin replacement improved QOL with a small effect size (d = 0.18), well-being with a medium effect size (d = 0.47), and health status with a small effect size (d = 0.26).Although the separate effects of somatropin on QOL, health status, and well-being could not be compared to placebo, we concluded that somatropin treatment most likely plays a role in improving the well-being of patients with GHD. This conclusion is based on correlations that have been found between IGF-I levels and parameters of well-being, such as anxiety and depression.

Recombinant growth hormone treatment, osteoporosis and fractures, more complicated than it seems!

Human growth hormone.