Growth Hormone Dose Research Articles

Factors Influencing the Incubation of an Infectious Form of Creutzfeldt-Jakob Disease

The French epidemics of iatrogenic Creutzfeldt-Jakob disease after growth hormone (GH) treatment provide an opportunity to understand factors governing the inter-human transmission of prions. The present analysis relying on truncated Weibull distribution supports a relationship between host genetics, dose of the at-risk GH, age at treatment onset, and duration of the incubation period.

Evaluation of Safety and Efficacy of Growth Hormone Therapy by IGF-1 Z Score in Children with Short Stature.

This study aims to explore the safety and efficacy of growth hormone (GH) therapy by retrospectively analyzing the changes of insulin-like growth factor-1 (IGF-1) Z-scores in children with short stature after treatment with GH. The etiology of 104 children with short stature was classified according to the GH stimulation test and IGF-1 levels: (1) growth hormone deficiency (GHD); (2) mild growth hormone deficiency (M-GHD); (3) idiopathic short stature (ISS); (4) GH insensitivity syndrome (GHIS). In addition, all patients were treated with recombinant human growth hormone (rhGH) for 12months, and the growth rate (Gv), height, body mass, bone age, height standard deviation scores (HtSDS), IGF-1 and adverse reactions were compared among these three groups before and after treatment. The height, body mass, Gv and HtSDS were significantly higher in each group compared with those before treatment. Furthermore, the Z-score of IGF-1 significantly increased after 1month of GH treatment and was positively correlated with the dosage of GH. Moreover, the difference in standard deviation score was significantly positively correlated with the increase in standard deviation score of IGF-1. The detection of the GH-IGF-1 axis function can be carried out for the etiologic diagnosis of short stature. IGF-1 increased after rhGH treatment, and IGF-1 level was correlated to the time of therapy and dosage of GH. IGF-1-based GH dosing targeted to age- and gender-adjusted means may save medical costs and offer a more dose-sparing and potentially safer mode of therapy compared with traditional weight-based dosing.

Height Gain and Safety Outcomes in Growth Hormone-Treated Children with Idiopathic Short Stature: Experience from a Prospective Observational Study

Background/Objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice. Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data. Results: Compared to children with isolated idiopathic GH deficiency (IGHD), those with ISS were shorter at baseline but had similar age and GH dose. Mean ± SD height SD score (SDS) increase was similar for ISS and IGHD, with 0.6 ± 0.3 (first), 0.4 ± 0.3 (second), 0.3 ± 0.3 (third), and 0.1 ± 0.3 (fourth year) for ISS. Girls with ISS (27% of subjects) were younger and shorter than boys but had similar height gain over time. At NAH in the ISS group (n = 467), mean ± SD age, GH duration, and height SDS were 17.3 ± 2.3 years, 4.6 ± 2.7 years, and –1.2 ± 0.9, respectively. Height gain from baseline was 1.1 ± 1.0 SDS and was greater for boys than girls (1.2 ± 1.0 vs. 0.9 ± 0.9), but boys were treated longer (5.1 ± 2.8 vs. 3.6 ± 2.5 years). Adverse events were reported for 24% with ISS versus 20% with IGHD – most were common childhood conditions or previously reported in GH-treated patients. Conclusions: GH-treated children with ISS achieved substantial height gain, similar to patients with IGHD. Fewer GH-treated girls were enrolled than boys, but with similar height SDS gain over time. No ISS-specific safety issues were identified. Thus, GH treatment of ISS appears to have a safety/effectiveness profile similar to that of IGHD.

SAT-282 Outcomes in Children Treated with Growth Hormone for Prader-Willi Syndrome: Data from the Answer® Program and Nordinet® International Outcome Study (IOS)

Background: The American Norditropin® Studies: Web-Enabled Research (ANSWER) Program and the NordiNet® International Outcome Study (NordiNet® IOS) are complementary, large-scale, non-interventional studies designed to gather long-term data on the effectiveness and safety of Norditropin® (somatropin) treatment in the usual clinical setting. Data were collected in the United States (US) and Europe from 2006 to 2016 in both children and adults. Objective: To assess the clinical outcomes of growth hormone (GH)-treated pediatric patients with Prader-Willi Syndrome (PWS) enrolled in the ANSWER® Program or NordiNet® IOS. Methods: Patient information was entered by participating physicians using a web-based data entry tool. Change from baseline in height standard deviation scores (HSDS) and body mass index standard deviation scores (BMI SDS) were analyzed based on availability of follow-up data. The explanatory variables in the repeated measures model analysis included baseline HSDS/BMI SDS, gender, age, target height, region (US/Europe), and GH dose. Results: From a total of 129 PWS GH-naïve patients, available data for HSDS and BMI SDS analysis included 129 and 98 patients respectively on a GH dose of 0.03 (±0.01) mg/kg/d. In the HSDS analysis with equal number of males and females, the mean age at the start of treatment was 4.42 (±4.51) years, and mean treatment period was 2.48 (±1.31) years. Further analysis determined that baseline age and years on treatment had a significant impact on the change in HSDS (P=0.014 and P<0.0001, respectively. In the BMI SDS analysis, 51% were males. At the start of treatment, the mean age was 5.56 (±4.79) years, with a mean duration of GH treatment of 2.45 (±1.32) years. The mean BMI was 18.04 (±4.9) for NordiNet® patients and 24.68 (±7.75) for ANSWER® patients. The baseline BMI SDS of NordiNet® patients (0.4±1.54) was lower compared with that of ANSWER® patients (1.80±1.68). Longer GH treatment time lead to a greater change in BMI SDS from baseline (P<0.0001). In addition, those patients with a higher BMI at the start of treatment had a greater decrease in BMI over time [t(624)=-8.01, P<0.0001]. Conclusions: GH is effective in the management of children with PWS. Earlier treatment resulted in a greater gain in height, and longer treatment period resulted in better outcomes for both height and BMI.

SAT-049 Growth Hormone Treatment in Mexican Turner's Syndrome

INTRODUCTION: Turner syndrome(TS) is a chromosomal disorder that occurs in one of every 2500 live births, characterized by the complete or partial absence of a chromosome X (the complete monosomy [45,X] accounts for more than 50% of cases), although some studies have found evidence of a high prevalence of mosaicism. It is associated with a range of phenotypic characteristics, chief of which are short stature, gonadal dysgenesis, hand and foot lymphoedema, pterygium colli, cubitus valgus and cardiovascular malformations, among others. Growth failure is a cardinal feature of TS, which may impair their quality of life, and adult patients have a mean height approximately 20 cm lower than that of unaffected women of the same ethnic group. METHODOLOGY: A study performed in the outpatient clinic of pediatric endocrinology of the National Institute for Pediatrics, descriptive, retrospective in 19 patients with Turner syndrome confirmed with karyotype, was followed up for 1 year in growth hormone treatment, size, weight was determined , Body mass index, growth rate at the beginning and at the end of the treatment. In addition, serum glucose, glycosylated hemoglobin was determined at the beginning and end of treatment. Statistical analysis was performed in the SPSS version program. RESULTS: We evaluated 19 patients with mean age 9 years +3.51, the average of the dose of growth hormone was of 1.43mg / day the size before treatment was an average of 114.73 with a SD:-3.06, showing improvement in the posterior size to treatment with an average of 119.25 SD:-2.7. In addition, the Body Mass Index was assessed with an average of 24.63 + 9.9 and at the end of treatment 27.98 +10.4. Regarding the growth rate, it is observed prior to the treatment Media 4.3 DE: 1.66 and the growth rate after the average treatment: 17.5 DE: 3.42 Levels of glycosylated hemoglobin (HBA1C) were assessed at the start of treatment with a mean of 5.3 (4.2- 5.7) and at the end of treatment the average of HBA1C 5.59 (4-6). DISCUSSION AND CONCLUSIONS: The short stature in TS is the fundamental finding and may be present in the absence of other clinical manifestations.The use of rhGH to increase the speed of growth and final height in patients with TS is an accepted and endorsed by different study. It has been observed in international studies that gains of 5-10cm are obtained with respect to the final size. It should start when the size is below -2 SDS with respect to the population mean or when the growth rate is lower than the 10th percentile for their bone age.The study that is presented is 12 months after the start of the treatment, an increase in the speed of growth as well.

Efficacy and safety of replacement treatment in isolated growth hormone deficiency

IntroductionGrowth in patients with isolated growth hormone (GH) deficiency is heterogeneous despite treatment due to the low specificity of diagnostic tests, making it necessary to define efficacy variables. AimsTo evaluate efficacy of hormone replacement therapy in children with isolated GH deficiency. MethodsObservational-ambispective study of patients treated in our department in the last 14 years for isolated GH deficiency. This was defined as a GH level less than 7.4mg/dL in response to 2 stimulation tests in patients with height<2SD and a decreased growth rate. ResultsThe study included a total of 97 patients, of whom 69% were boys. The large majority (89.58%) achieved final height. None of them had side effects. The median dose of GH used was 0.028mg/kg/day (0.03–0.025). There was a gain of 1.17 SD in final height. Around three-quarters (71.13%) of the patients were reassessed in adulthood, of whom 39.4% maintained the deficiency, and 79.31% achieved target range height. Target height, estimated height, and the total pubertal gain were positively correlated with final height, while the bone age/chronological age ratio and the initial insulin-like growth factor-1 showed a negative correlation. ConclusionsA majority of patients reached target size, although only a few of them maintained the deficiency in adulthood. Target size, estimated adult height, and pubertal variables are directly related to adult height, while bone age/chronological age and insulin-like growth factor-1 were inversely related, and these can be used as efficacy variables. No adverse effects were observed in the sample with the doses used for the treatment.

Needle-Free and Needle-Based Growth Hormone Therapy in Children: A Pooled Analysis of Three Long-Term Observational Studies

Background: Treatment with growth hormone (GH) is standard clinical practice in children with GH deficiency (GHD) or Turner syndrome (TS). Hitherto, no long-term data on auxological outcome and safety of Zomacton® have been published. Data comparing needle-free administration (NF) and needle injection (NI) of GH are very sparse. Aims: To analyse longitudinal auxological outcome and safety data of GH treatment-naïve patients diagnosed with GHD or TS and to compare NF and NI in a real-life setting. Methods: Pooled auxological data and safety information from three consecutive prospective observational Zomacton® studies covering 22 years of treatment were analysed and NF was compared to NI. Results: The safety cohort comprised 1,595 patients who received at least one GH dose. The auxological outcome cohort comprised 856 treatment-naïve patients with follow-up data ≥12 months. Height-SDS and height velocity improved significantly during the first 3 years of treatment. Documented choice of device was available for 658 patients (NF 69.1%, NI 30.9%). NF administration was non-inferior to NI. No previously unknown safety signals occurred. Conclusion: Real-life data show that treatment with Zomacton® improves auxological outcome parameters without new safety concerns. NF administration of GH represents a useful alternative to NI in children with growth disorders.

Short- and long-term responsiveness to low dose growth hormone (GH) in adult GH deficiency: Role of GH receptor polymorphism.

In patients with growth hormone (GH) deficiency (GHD), low doses of recombinant human GH (rhGH) have a similar or better long-term clinical effect than higher doses. Pharmacogenetic studies suggest that GH receptor (GHR) polymorphism only influences some metabolic parameters. Nonetheless, there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of our prospective study was to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short- (6 and 12months) and long-term (5years) follow-up. Sixty-nine GHD adult patients were studied, before and during treatment with rhGH, using a standardised low-dose protocol calculated on the basis of body weight (0.01-0.03mgkg-1 week-1 ) and monitored by an insulin-like growth factor (IGF)-I plasma assay, as well as anthropometric and metabolic parameters. The GHR genotype (flfl, fld3 or d3d3) was determined from the peripheral blood. d3-GHR carriers showed a more effective short- and long-term response to low rhGH dose with respect to low-density lipoprotein reduction, body composition and blood pressure (homozygous patients only); d3-GHR homozygosity is related to a significant IGF-I increase during short-term follow-up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF-I increase at 6 and 12months of replacement therapy. The d3d3-GHR genotype may influence some metabolic effects during the short- and long-term follow-up of low rhGH dose and could be an independent determinant of the increase of IGF- I during short-term follow-up.

Efficacy and safety of recombinant growth hormone treatment in children with growth retardation related to long-term glucocorticosteroid therapy

ObjectiveTo evaluate safety and efficacy of recombinant human growth hormone treatment in children on long-term glucocorticoid therapy. MethodsA 5-year prospective open-label study included children on glucocorticoid therapy with either standard deviation score (SDS)<−2 for height for chronological age (CA) if naïve to growth hormone treatment, or annual growth rate≥0 SDS for CA if currently receiving growth hormone. ResultsNinety-eight patients began treatment, 63 discontinued; 59 were analyzed for safety and 58 for efficacy. There was male predominance (78.0%). Median age was 13.0 years. Median height screening was 136.0cm (range, 95.1–159.7cm). Mean SDS for height for CA in the efficacy analysis set was −2.91±1.19 (range, −7.49 to −0.96). Mean growth hormone dose was 0.4, 0.4, 0.4 and 0.3mg/kg/week at month 0, M12, M24, and M36, respectively. Primary analysis of change in SDS for height for CA from baseline to M36 showed a significant increase of 0.80±1.03. Twenty patients in the safety analysis set had≥1 treatment-emergent adverse event (TEAE) related to study treatment. Two patients experienced serious treatment-related TEAEs: 1 case of poor compliance, and 1 of mild hyperglycemia, both already observed under growth hormone treatment. ConclusionThis study suggests that growth hormone treatment could be effective in increasing height in children on long-term glucocorticoid treatment with a safety profile comparable to that in approved rhGH treatment indications. Clinical trial registrationNCT00163189.

Evidence that growth hormone can improve mitochondrial function in oocytes from aged mice.

Decline in successful conception decreases more rapidly after 38 years of age owing to follicular depletion and decreased oocyte quality. However, limited information is available regarding the underlying mechanism and the useful treatment. This study aimed to evaluate the effects of growth hormone supplementation on oocyte maturation in vivo in aged and young mice and to determine its effect on mitochondrial function. The influence of three different doses of recombinant human growth hormone (rhGH) (0.4, 0.8 and 1.6 mg/kg/day) for 8 weeks before ovarian stimulation was analyzed. Superovulated oocytes were released from the oviduct of 12-week-old and 40-week-old female C57BL/6J mice 14–16 h after administration of human chorionic gonadotropin. Ovarian follicle and morphological analysis and oocyte maturation parameters were then evaluated. This study is the first, to our knowledge, to report that medium- and high-dose rhGH significantly increases antral follicles in aged mice but anti-Müllerian hormone (AMH) levels. Furthermore, derived oocytes, MII-stage oocyte rate, ATP levels, mitochondrial membrane potential and frequencies of homogeneous mitochondrial distribution increased. In contrast, in both aged and young mice, the mtDNA copy numbers per oocyte were similar before rhGH administration, and upon saline administration, they did not differ significantly. We conclude that medium-dose rhGH supplementation before standard ovarian stimulation regimens improves oocyte quality in aged mice, probably by enhancing mitochondrial functionality.

Idiopathic Short Stature Phenotypes among Korean Children: Cluster Analysis.

Idiopathic short stature (ISS) is a heterogeneous group and their responsiveness to growth hormone treatment varies among individuals. The aim of this study was to identify homogeneous phenotypes to better assess response before the initiation of treatment. We focused on person-centered approaches using a latent profile analysis. Clinical data of 218 children (127 boys and 91 girls) aged 4-15 years were obtained from the "LG Growth Study" which is a non-interventional Korean multicenter registry for growth hormone treatment. Growth hormone dose, first-year difference in height standard deviation score (Δheight SDS), mid-parental height SDS, and initial bone age were inputted into the model. The distribution of scatter plot was clearly distinguished at the chronological age of 8.83 years, Δheight SDS of 0.82 and mean GH dose of 0.36 mg/kg/week. The latent profile analysis revealed three distinct phenotypes names as follows: younger good responder (n = 56), older good responder (n = 111), and older poor responder (n = 51) groups. Despite more than twice the mean growth hormone dose, the older poor responder group showed the least improvement in the mean Δheight SDS. The pretreatment height velocity and peak growth hormone level were lower for the older poor responder group compared with those of the older good responder group. The statistically optimal cutoff point for predicting poor response was 3.41 cm/year for pretreatment height velocity and 9.18 ng/mL for peak growth hormone level. This study offers a new multidimensional approach to enable personalized growth hormone treatment optimization according to ISS phenotypes.

Biological behavior of 60/40 biphasic calcium phosphate and growth hormone mixture: in vivo study in dogs

Grafting materials are important for ridge preservation procedures after tooth extraction. Ridge preservation prime value is the volume preservation for the healing sockets, which is needed for different ridge augmentation procedures. Objective: Determine the healing responses of (local growth hormone, and biphasic calcium phosphate mixture 60/40 in fresh extraction sockets of a canine model.Materials and Methods: Six mongrel dogs included in this study; they were divided into 2 groups according to the time of sacrifice (4 and 8 weeks). Each of these groups includes three animals. Animals subjected to extraction of the fourth premolar bilaterally, The right side treated with a mixture of 4 IU (1.6 mg) Growth hormone and biphasic calcium phosphate (a composite of hydroxyapatite HA and beta-tricalcium phosphate TCP 1 x 0.15 ml (450-650 µm) in a granular form, while the left side left as a control. The healing extraction sockets were evaluated by surface electron microscope (SEM).Results: Scanning electron microscope examination showed homogenous new bone formation in both groups. Control group showed significant results as regard calcium phosphate ratio in the first month, while non-significant result was encountered in the second month between two groups. Conclusion:. Single local dose of growth hormone mixed with 60/40 biphasic calcium phosphate did not improve calcium phosphate ratio.

Growth hormone therapy in patients with Noonan syndrome.

Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.

Effect of adherence to growth hormone treatment on 0-2 year catch-up growth in children with growth hormone deficiency.

BackgroundQuantifying the association between adherence and the growth response to growth hormone (GH) treatment is hampered by suboptimal methods of measuring adherence, confounders associated with the growth response, and restriction of the outcome parameters to yearly growth velocities.AimTo investigate the effect of adherence on the two-year growth response to GH treatment in prepubertal children with idiopathic isolated growth hormone deficiency (GHD) participating in the easypod connect observational study (ECOS), a 5-year, Phase IV open-label study to continuously assess real-world adherence via the easypod electronic drug-delivery device.Patients and methodsOutcome measures were change in height standard deviation score (ΔHSDS), index of responsiveness (IoR), and parameters of two catch-up growth (CUG) curve functions (monomolecular growth curve and second degree polynomial) with adj-HSDS (HSDS minus Target height (TH) SDS) as dependent variable. Inclusion criteria were GHD, naïve to GH treatment, known TH, age <10y in girls and <12y in boys, ≥3 measurements, HSDS <-2 at start, complete data on growth and adherence in the first and second year. Linear regression analyses were performed to test the association between adherence (continuous and high vs. low) and the outcome measures, also adjusted for potential clinical confounders (age at start, adj-HSDS at start, birth weight SDS, gestational age (<37 weeks vs ≥37 weeks), GH dose, GH max (n = 58)). The formula of IoR already adjusts for confounders.ResultsIn total, 95 patients complied with the inclusion criteria. The strongest associations were found between high adherence in the second year (≥91% as cut-off value) and IoR 2y (+0.62), and average adherence and high adherence (≥78%) in the first two years and ΔHSDS 0-2y (+0.11 SD per 1 injection/week, and +0.34 SD for high vs. low adherence).ConclusionSuboptimal adherence negatively affected the growth response in the first two years of GH treatment.

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged.

Variation of bone acquisition during growth hormone treatment in children can be explained by proteomic biomarkers, bone formation markers, body composition and nutritional factors.

Growth hormone (GH) regulates both longitudinal growth and bone acquisition in children, and has profound metabolic effects. The aim was to investigate the association between proteomic biomarkers, body fat, nutrition and bone formation markers, and longitudinal growth in response to GH during the first year of treatment. The degree to which changes in these factors could explain variations in GH-dependent longitudinal growth and bone mineralization was also assessed. The individualized GH dose trial included 128 short prepubertal children with either normal (non-GH-deficient) or reduced levels of GH secretion (GH-deficient) (mean age ± SD, 8.6 ± 2.6 years; 90 boys), i.e., with a broad range of GH-secretion and GH-responsiveness, receiving GH treatment (mean 43 μg/kg/day). Blood samples were taken and dual-energy X-ray absorptiometry (DXA) measured at baseline and 1 year of treatment. Step-wise multiple regression models were constructed including three steps with different independent variables added at each step to explain the variance in outcome variables (heightSDS, bone mineral content (BMC) and bone mineral density (BMD). Independent variables included in Step I were previously identified proteomic markers related to GH treatment response, bone formation markers (intact PINP, bone-specific alkaline phosphatase and osteocalcin), variables at treatment start (GH dose mU/kg/day, GH maximum secretion, and difference between child's current and mid-parental heightSDS). Step II explored the added influence of body composition data (body mass index or DXA). Step III explored the added influence of serum nutritional markers and hormones. Step I variables explained 71% of the variation in first year heightSDS gain, median (minimum-maximum) 0.8 (0.24-1.67); and the proportion explained rose to 73% following inclusion of step II variables and 75% following step III. Corresponding values for total body BMC were 58%, 78%, and 80%, respectively. Proportions fell by approximately 20% when BMC was adjusted for height; 33%, 57%, and 57% for steps I, II, and III, respectively. Corresponding values for total body BMD were 29%, 39%, and 45%, respectively. For total BMC, as much as 80% of the variation during the first year of GH treatment could be explained by proteomic biomarkers, body fat, nutrition and bone formation markers, whereas for height-adjusted BMC 57% could be explained. The inclusion of information about either body composition (fat/lean mass) or nutritional markers contributed with approximately 20%. The variation in heightSDS gain could be explained to 75%. Hence, information of fat or nutrition markers was needed for explaining the variation in bone acquisition to the same magnitude as explaining the variation in height response.

Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency

BackgroundThe aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment.MethodsA randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of − 2 to − 1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires.ResultsData from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor.ConclusionsThe adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor.Trial registrationThis study is registered with ClinicalTrials.gov, number NCT01877512.

PENGGUNAAN HORMON PERTUMBUHAN REKOMBINAN TERHADAP PERTUMBUHAN IKAN SELAIS (Ompok hypopthalmus)

This study was aimed to determine the best dose of recombinant growth hormone on the growth of selais fish (Ompok hypopthalmus). This study used a complete randomized desigh with one factor that is recombinant growth hormone dose and 3 repetition. The dose given were 0 mg/kg, 6 mg/kg, 12 mg/kg, 18 mg/kg and 24 mg/kg. The results showed that addition of rElGH at dose of 12 mg/kg were the best dose for selais fish growth’s parameters; absolute length growth (3,60± 0,6 cm), absolute weight growth (3,85 ± 0,46 g), daily growth rate (5,56 ± 0,32 %), food convertion ratio (1,10 ± 0,12), protein and fat retention (46,73 ± 21,34 % and 103,83 ± 21,43 %). The highest level of glycogen muscle (22,43 ± 0,61 mg/g) was found in addition of rElGH at dose of 18 mg/kg.

Evaluation of glucose metabolism in children with growth hormone deficiency during long-term growth hormone treatment.

Growth hormone (GH) affects carbohydrate metabolism through direct negative effect on insulin sensitivity and indirectly, via insulin-like growth factor-1 (IGF-1), which exerts positive insulin-mimetic action. The aim of this retrospective study was to evaluate the influence of long-term GH treatment on glucose homeostasis in 118 children with isolated idiopathic GH deficiency (GHD). Based on this analysis we wanted to determine the usefulness of glycated haemoglobin (HbA1c) and parameters derived from the oral glucose tolerance test (OGTT) in the monitoring of disturbed glucose metabolism during GH treatment and to assess the value of IGF-1 in prediction of those changes. Mean duration of GH treatment was 2.5 ± 1.2 years. Data were analysed in the whole group and according to baseline pubertal status. Significant increases in insulin concentrations, both fasting and during the OGTT, accompanied by a significant increase in fasting glucose and unchanged glucose concentrations during the OGTT, were found after the initiation of GH treatment. HbA1c did not change significantly during GH treatment in comparison to baseline values and remained normal, even in patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) found during GH treatment. Changes in glucose metabolism observed after the onset of GH treatment were related to increment in IGF-1 SDS and to GH doses. Significant associations between changes in IGF-1 SDS in the first year of GH treatment and some of the glucose metabolism parameters evaluated after the first, the second and the third year of GH treatment were also confirmed in multiple regression analysis after taking the GH dose into consideration. All cases of IFG and/or IGT detected during GH treatment are reversible after dietary intervention, independently of pubertal status, and do not lead to diabetes mellitus.

Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study.

Country-specific data on outcomes of treatment with recombinant human growth hormone are lacking. We present such data for children treated with growth hormone in Canada. We describe characteristics and outcomes of 850 children (mean age at baseline 8.5 yr) treated with growth hormone constituting the Canadian cohort of the multinational phase IV prospective observational Genetics and Neuroendocrinology of Short-stature International Study (GeNeSIS). The diagnosis associated with short stature was as determined by the investigator. Auxological data were evaluated yearly until near-adult height. Adverse events were assessed in all growth-hormone-treated patients. The diagnosis ascribed as the cause of short stature was growth hormone deficiency in 526 children (61.9%), predominantly organic rather than idiopathic, particularly congenital pituitary abnormalities and intracranial tumours. All diagnostic groups with sufficient patients for analysis had increased height velocity standard deviation score (SDS) and height SDS during growth hormone treatment. For patients who reached near-adult height (n = 293), the mean height SDS was within the normal range for about 80% of patients with organic growth hormone deficiency (n = 131) or idiopathic growth hormone deficiency (n = 50), 50% of patients with idiopathic short stature (n = 10) and 46% of patients with Turner syndrome (n = 79). Eleven deaths were reported, 7 in patients with organic growth hormone deficiency. Serious adverse events considered related to growth hormone treatment (n = 19) were isolated except for medulloblastoma recurrence (n = 2) and adenoidal hypertrophy (n = 2). Growth hormone treatment was effective and had a good safety profile in Canadian children. Growth hormone dosages were lower than in the US and global GeNeSIS cohorts, and a greater proportion of treated Canadian children had organic growth hormone deficiency. ClinicalTrials.gov, no. NCT01088412.