Doses Of Recombinant Growth Hormone Research Articles

Chronic kidney disease and growth failure: Efficacy of growth hormone treatment

Growth failure is a frequent complication observed in children with chronic kidney disease (CKD) and correlated to increased morbidity and mortality. To achieve a normal growth in children with CKD remains challenging for pediatric nephrologists. Growth failure in the setting of pediatric CKD is multifactorial and related to an impaired sensitivity to growth hormone and to a deficiency of IGF1 (insulin-like growth factor1). Growth failure management has improved during the last two decades and consists of correcting any nutritional and metabolic abnormalities, of an improvement of dialysis for children on end-stage renal disease, and of an administration of a supraphysiologic dose of recombinant growth hormone to overcome GH insensitivity. This article summarizes the causes, outcomes and assessment tools of growth in children with CKD as well as the management of recombinant growth hormone.

Оцінка ефективності лікування пацієнтів з ознаками затримки внутрішньоутробного розвитку при оптимізації дози препаратів рекомбінантного гормону росту

Актуальність. Згідно зі світовими статистичними даними, близько 5–10 % новонароджених мають затримку внутрішньоутробного розвитку (ЗВУР) — народжуються з малою масою та/або низькою довжиною тіла щодо свого гестаційного віку. Внаслідок неадекватних темпів постнатального росту у таких дітей до 2-річного віку відзначається відставання в рості. Цей дефіцит прискорення росту спостерігається протягом усього дитинства і підліткового періоду, що у кінцевому підсумку призводить до низькорослості у дорослому віці. Мета: проаналізувати ефективність терапії різних дозових рівнів препаратів рекомбінантного гормону росту (рГР) з метою корекції росту у дітей допубертатного віку з ознаками затримки внутрішньоутробного розвитку. Матеріали та методи. Обстежені 50 дітей (16 дівчаток і 34 хлопчики) з відставанням у рості (середній вік — 6,82 ± 0,36 року), які народилися з ознаками ЗВУР. За результатами тестів із клонідином та інсуліном, пацієнтів з ознаками ЗВУР було розподілено на дві групи: група А — діти без соматотропної недостатності (n = 34; 68 %), група Б — пацієнти з дефіцитом гормону росту (n = 16; 32 %). Група контролю включала 34 пацієнтів (середній вік — 6,58 ± 0,38 року) із соматотропною недостатністю — 13 дівчаток і 21 хлопчика. Усі пацієнти отримували лікування рекомбінантним гормоном росту, починаючи з дози 0,03 мг/кг/добу згідно з протоколом для гіпофізарного нанізму; у разі незадовільної швидкості росту дозу поступово збільшували до 0,05 мг/кг/добу у пацієнтів групи Б. Результати. Вірогідне сповільнення прискорення росту в перші 6 місяців лікування рГР у дозі 0,033 мг/кг/добу було виявлено у пацієнтів з ознаками ЗВУР без соматотропної недостатності (р < 0,05). При лікуванні рГР у дозі 0,05 мг/кг/добу протягом наступних 6 місяців відбулося статистично значуще збільшення коефіцієнта стандартного відхилення SDS (Standard Deviation Score) росту пацієнтів з ознаками ЗВУР без соматотропної недостатності (–2,0 ± 0,14 SDS проти –2,58 ± 0,15 SDS перших 6 місяців з дозою рГР 0,033 мг/кг/добу) (р < 0,05). Висновки. Оптимальною дозою рГР для лікування дітей з ознаками ЗВУР із соматотропною недостатністю є 0,033 мг/кг/добу, а у пацієнтів з ознаками ЗВУР без дефіциту гормону росту — 0,05 мг/кг/добу.

The influence of growth hormone therapy on the cardiovascular system in Turner syndrome.

Short stature, ovarian dysgenesis, infertility, and cardiovascular malformations are classic features in Turner syndrome (TS), but the phenotypical spectrum is wide. Through early diagnosis and appropriate treatment, TS patients have a chance to achieve satisfactory adult height and sexual development. The doses of recombinant growth hormone (rGH) used are usually higher than the substitution dose. The safety aspects of this therapy are very important, especially in terms of the cardiovascular system. The presented study aimed to analyze how the rGH therapy may influence the cardiovascular system in TS based on current literature data. We conducted a systematic search for studies related to TS, cardiovascular system, and rGH therapy. The results show that rGH seems to have a positive effect on lipid parameters, reducing the risk of ischemic disease. It is additionally optimized by estradiol therapy. Although rGH may increase insulin resistance, the metabolic derangement is rare, probably due to lower fat content and an increase in lean body mass. Several studies showed that rGH treatment could cause aorta widening or increase the aorta growth rate. IGF-1 can be independently associated with increased aortic diameters. The studies analyzing the impact of GH on blood pressure show conflicting data. The proper cardiovascular imaging before and during rGH treatment and detecting the known risk factors for aorta dissection in every individual is very important. The long-term effects of growth hormone treatment on the heart and arteries are still not available and clearly estimated and have to be monitored in the future.

Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH.

The detection of low doses of recombinant growth hormone is a challenge in antidoping testing. Future testing may lead toward the longitudinal monitoring of IGF-I and P-III-NP in an endocrine module. Additional biomarkers, for example vitamin D binding protein, alpha-HS-glycoprotein, fibronectin 1, and decorin have been identified in different omics studies. This was a longitudinal study of the usefulness of these putative biomarkers in relation to 2 weeks administration of low doses of recombinant growth hormone in healthy male volunteers. Moreover, the hematological parameters included in the athlete biological passport were studied as well as the serum concentration of testosterone and dihydrotestosterone. Fibronectin 1 increased by 20% during the treatment period (P ˂ 0.05), confirming the previous finding. Alpha-HS-glycoprotein decreased by 25% up to 3 weeks after treatment (P ˂ 0.05), contradicting previous results. The addition of fibronectin 1 increased the likelihood of detecting recombinant growth hormone intake based on individual calculated thresholds in some of the participants compared with the GH2000, IGF-I, and P-III-NP. The multiplication of fibronectin 1 concentration by IGF-I resulted in the most profound (up to 4-fold) changes. A minor 15% increase (P = 0.003) in the reticulocyte percentage was observed, but the changes did not lead to any atypical profile based on individual passport thresholds. Vitamin D binding protein, decorin, testosterone, and dihydrotestosterone were not affected by growth hormone. Dihydrotestosterone sulfate was negatively correlated with IGF-I at baseline (R = -0.50, P = 0.003) and post dose (R = -0.59, P = 0.01). In conclusion, fibronectin 1 was verified as a promising future biomarker for detecting low doses of recombinant growth hormone.

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.

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.

Association of the Exon 3 Deleted/Full-Length GHR Polymorphism with Recombinant Growth Hormone Dose in Growth Hormone-Deficient Adults

Contradictory reports exist regarding the influence of the exon 3 deleted (d3)/full-length (fl) growth hormone receptor (GHR) polymorphism on responsiveness to recombinant human growth-hormone therapy in idiopathic short stature, small for gestational age and GH-deficient children, Turner syndrome patients and GH-deficient adults. In some of these studies, the d3 allele was associated with increased responsiveness to GH. The aim of this study was to test this association in a group of GH-deficient adult patients receiving recombinant GH treatment. Patients were derived from the prospective German Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. The GHRd3/fl polymorphism was determined in 133 German adult patients (66 men and 67 women; mean age: 45.4 years +/- 13.1 standard deviation; majority Caucasian) with a GH-deficiency of different origin. Patients received GH treatment for 12 months with a finished dose-titration of GH and standardized insulin-like growth factor (IGF)-1 measurements in one central laboratory. GH dose after 1 year of treatment, IGF-1 serum concentrations, IGF-1 standard deviation score (SDS) values and anthropometric data were analyzed by GHRd3/fl genotypes. After 1 year of GH treatment, the individually required GH dose was significantly lower in GH-deficient patients carrying one or two d3 alleles, compared with patients with the full-length receptor (p = 0.04). Genotype groups (d3-allele carriers vs noncarriers) showed no significant differences in IGF-1 serum concentrations (p = 0.51), IGF-1 SDS (p = 0.36) nor in gender (p = 0.53), age (p = 0.28), weight (p = 0.13), height (p = 0.53) or BMI (p = 0.15). The d3-allele carriers required approximately 25% less exogenous GH compared with the homozygous fl-allele carriers, which may express an increased responsiveness to exogenous GH. Variability of the individually required GH dose in adult GH-deficient patients may therefore be partly due to the GHRd3/fl polymorphism. Further studies are required to confirm these results.

Final Height in Children with Idiopathic Growth Hormone Deficiency Treated with a Fixed Dose of Recombinant Growth Hormone

There is no consensus regarding the optimal dosing of recombinant human growth hormone (rhGH) for children with growth hormone deficiency (GHD). Our objective was to evaluate the final adult height (FAH) in children with idiopathic GHD treated with a fixed rhGH dose of 0.18 mg/kg/week. We reviewed all charts of patients with idiopathic GHD treated with rhGH since 1985 who reached FAH. Ninety-six patients were treated for an average of 5.4 years. The mean age was 11.9 years, the mean height –2.87 standard deviation score (SDS) and the mean FAH was –1.04 SDS. Females had a lower predicted adult height than males at the initiation of therapy (–2.0 vs. –1.01 SDS; p = 0.0087) but a higher FAH – predicted adult height (1.08 vs. 0.04 SDS; p = 0.0026). In multiple regression analysis, the FAH SDS was positively related to the midparental height SDS, the height SDS at GH initiation and growth velocity during the first year of therapy, and negatively correlated with peak GH and bone age at initiation (r² = 0.51; p < 0.005). Treatment of children with idiopathic GHD with a fixed dose of 0.18 mg/kg/week rhGH is sufficient to reach FAH within 2 SDS of the normal population range (84%) with an average FAH within –0.5 SDS of midparental height.

Effects of growth hormone and/or testosterone on very low density lipoprotein apolipoprotein B100 kinetics and plasma lipids in healthy elderly men: A randomised controlled trial

Objective To assess the effects of low dose recombinant growth hormone (GH), testosterone (T) and combined GH and T, on lipid profiles and very low density lipoprotein apolipoprotein B (VLDL apoB) metabolism. Design and patients Sixty-nine healthy elderly men (65–80 yr) were studied in a six month double-blind, placebo-controlled trial. Participants were randomised to placebo GH and placebo T (P), GH and placebo T (GH), T and placebo GH (T) or GH and T (GHT). Measurements Plasma lipid profiles were assessed before treatment and at 6 months. VLDL apoB absolute secretion rate (ASR) and fractional catabolic rate (FCR) were measured in a subset of 21 men: P ( n = 5); GH ( n = 5); T ( n = 6); GHT ( n = 5), with an infusion of 1- 13C leucine. Fat mass (FM) was measured by DEXA and intra-abdominal fat (IAF) by CT scan. Results IGF-I levels increased in the GH and GHT ( P < 0.001) groups: testosterone increased in the T ( P = 0.029) and GHT ( P = 0.05) groups. There was no change in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B or lipoprotein(a) in the GH, GHT or T groups. In the subset of 21 men, IGF-I levels increased similarly with GH and GHT ( P < 0.01) but T levels increased only with T ( P < 0.03). FM and IAF decreased significantly only with GHT ( P < 0.01, P = 0.01). Treatment with GH, T or GHT had no effect on VLDL apoB ASR or VLDL FCR. Conclusion Co-administration of GH and T in near physiological doses in healthy elderly men resulted in favourable changes in body composition without altering the plasma lipid profile or VLDL apoB metabolism.

Dangers of growth hormone therapy in critically ill patients.

Prolonged length of stay is the major challenge for modern intensive care because of the associated morbidity and the impact on resource utilization. Severe trauma or infection is associated with a catabolic response, which is characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness, prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone has been applied as an experimental therapy for two decades in patients requiring parenteral nutrition and in patients with respiratory failure. Administration of recombinant growth hormone has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of recombinant growth hormone (with doses 10-20 times higher than used for replacement therapy) increases mortality of critically ill patients. The excessive mortality in patients treated with recombinant growth hormone was related to infections and development of multiple organ failure, leading to the conclusion that administration of high doses of recombinant growth hormone cannot be recommended for critically ill patients. This review reinforces that conclusion.

Current Dosing of Growth Hormone in Children With Growth Hormone Deficiency: How Physiologic?

The current doses of recombinant growth hormone (rGH) are two to three times those used in the pituitary growth hormone era. These rGH doses (0.025 to 0.043 mg/kg/d) are similar to or moderately greater than the physiologic requirements. Growth velocity and height gains have been shown to be greater with 0.05 mg/kg/d of rGH than with 0.025 mg/kg/d. Larger doses of GH and early initiation of treatment result in greater heights at the onset of puberty and greater adult heights. Earlier onset of puberty and more rapid maturation, as indicated by bone age, were not observed in children who were given 0.18 to 0.3 mg/kg/wk of rGH. The frequency of adverse events is very low, but diligent surveillance of all children who are treated with rGH is essential.