Human Growth Hormone Therapy Research Articles

Influence of growth hormone treatment on radiographic indices of the spine: propensity-matched analysis

BackgroundWe performed this study to investigate the influence of recombinant human growth hormone (rhGH) therapy on radiographic indices of the spine using propensity-matched analysis.MethodsPatients with idiopathic short stature who had undergone both growth hormone therapy and whole-spine radiographs more than twice prior to 15 years of age were included in the patient group. Other patients who had undergone whole-spine radiographs more than twice prior to the same age during regular checkups for idiopathic scoliosis formed the control group. Propensity-matched analysis was performed to reduce the selection bias. The scoliosis Cobb angle, coronal balance, apical vertebral translation, apical rotation, and pelvic obliquity were measured from the radiographs taken at the periodic follow-ups. The rate of progression of the measurements was adjusted by multiple factors using a linear mixed model with sex as the fixed effect and age and each subject as the random effects.ResultsUsing a propensity-matched analysis, 48 patients were finally included in both groups. The scoliosis Cobb angle increased by 1.0° (p < 0.001) per year in the patient group, whereas there was no significant annual change in the control group (p = 0.496). Female patients showed a greater scoliosis Cobb angle (1.8°, p = 0.039) compared with male patients. There was no significant difference between the patient and control groups in coronal balance (p = 0.264). Apical vertebral translation per year was increased by 1.2 mm (p < 0.001) in the patient group and 0.5 mm in the control group (p = 0.003).ConclusionRadiographic examination revealed that growth hormone therapy for idiopathic short stature affected the progression of the scoliosis Cobb angle and apical vertebral translation on the coronal plane. Physicians should be aware that annual follow-up is required to evaluate the change in the curvature of the spine in patients undergoing rhGH treatment.

Prevalence and Correlates of Adherence in Children and Adolescents Treated with Growth Hormone: A Multicenter Italian Study

To evaluate the self-reported prevalence of poor adherence to recombinant human growth hormone (rhGH) therapy in a large, representative sample of Italian children and adolescents and to assess treatment and patient level correlates of poor adherence. The study was conducted in 46 pediatric centers throughout Italy. A questionnaire was administered to consecutive children/adolescents treated with rhGH or their parents. Eligible patients were represented by subjects aged between 6 and 16 years, of both sexes, on rhGH treatment for at least 6 months. The questionnaire was administered to the person in charge of preparing the injection. Multivariable logistic regression analysis was performed to identify factors independently associated with adherence. Overall, 1,007 children/adolescents were involved, of whom 24.4% missed 1 or more injections during a typical week and were thus considered as nonadherent. The most frequently reported reasons for missing a dose were being away from home (33.3%), forgetfulness (24.7%), not feeling well (12.9%), and pain (10.3%). Multivariable analysis indicated association between poor adherence and adolescence, low level of parent education, longer duration of treatment, need to convince the child to inject, and low level of awareness of the consequences of not properly following treatment. The likelihood of adherence markedly increased with higher levels of perceived device convenience. Poor adherence is still a major problem in the treatment of growth disorders. Increasing awareness and reassessment of treatment adherence on an annual basis should be part of clinical practice of pediatric endocrinologists involved with rhGH treatment. CI = confidence interval GH = growth hormone rhGH = recombinant human growth hormone.

Fibrogenesis Imperfecta Ossium and Response to Human Growth Hormone: A Potential Therapy.

Fibrogenesis imperfecta ossium (FIO) is a rare bone disease manifested by generalized bone pain, fragility fractures, progressive disability, and extensive mineralization defect seen in bone biopsy specimens. The pathogenesis of the disease is unknown and currently there is no effective treatment. To report on the effect of recombinant human growth hormone (rhGH) therapy in FIO. An observational study in two patients. Endocrinology clinic in an academic institution. Two siblings with FIO. rhGH was administered subcutaneously at a dose of 1 U daily for 1 year. Changes in clinical, biochemical, radiological, and bone histological (i.e., light and transmission electron microscopy, and histomorphometry) investigations. Except for an elevated serum alkaline phosphatase level, results of routine biochemical, hematological, and hormonal investigations were normal in both patients. Radiographs showed pseudofractures and bone scans revealed a "beheaded" tracer activity pattern (i.e., superscan without uptake in the skull). Bone biopsy specimens showed severe mineralization defect simulating osteomalacia with disorganized collagen fibril alignment. Treatment with rhGH was followed by clinical, biochemical, and radiological improvement in both the patients, with substantial improvement in the mineralization defect, most likely due to rhGH-induced improvement in collagen fibril arrangement. We report on two brothers with FIO and demonstrate clinical improvement and restoration of normal bone pathology with rhGH therapy. We suggest that rhGH is a potential therapy for FIO for which no effective therapy currently exists.

Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women.

While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL). Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mgkg- 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations. rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST: p = 0.02; PRE vs. POST30: p = 0.007). This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.

Mortality and cancer incidence among patients treated with recombinant growth hormone during childhood in Israel.

The inconclusive evidence regarding long-term safety of recombinant human growth hormone (rhGH) therapy underlines the need for long-term large-scale cohorts. To assess long-term mortality and cancer incidence among patients treated with rhGH during childhood in Israel. A population-based cohort study. Data were retrieved from a national register established in 1988. Mortality data from the national population register were available through 31 December 2014. Data on cancer incidence from the national cancer registry were available through 31 December 2012. All patients ≤19 years approved for rhGH treatment during 1988-2009 were included. Patients were assigned to three risk categories, according to the underlying condition leading to growth disorder. All-cause mortality and cancer incidence rates were calculated, based on person-years at risk. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated, using the Israeli general population as a reference. Included were 1687 patients assigned to the low-risk category and 440 patients assigned to the intermediate-risk category. In the low-risk category, all-cause mortality and cancer incidence were not significantly different than expected (SMR 0·81, 95% CI 0·22-2·08 and SIR 0·76, 95% CI 0·09-2·73). In the intermediate-risk category, all-cause mortality and cancer incidence were significantly higher than expected (SMR 4·05, 95% CI 1·62-8·34 and SIR 4·52, 95% CI 1·22-11·57). No increased risk of mortality or cancer incidence was found in low-risk patients treated with rhGH during childhood. Patients with prior risk factors were at higher risk of both mortality and cancer.

Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

PurposePoor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod™, an electronic, fully automated injection device designed to track the time, date and dose administered.MethodsNinety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint—adherence to treatment—was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod™, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. ResultsThe easypod™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0–V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels.ConclusionsThe injection-recording system and other characteristics of easypod™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation

Background/Objective: In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers.Methods: 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n = 63) and 12 (n = 46–48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen.Results: Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups.Discussion: In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

Lichen planus-like drug reaction associated with recombinant human growth hormone therapy in a child patient with Turner syndrome

Turner syndrome (TS) is a genetic disease with an incidence rate of between 1:2000 and 1:5000 live female births. The treatment of TS differs according to age and Recombinant Human Growth Hormone (RHGH) therapy is usually given for the treatment of short stature in girls with TS in childhood. We describe the first case of a TS patient who presented with a clinical picture compatible with oral and palmoplantar lichen planus-like reaction during RHGH therapy; spontaneous remission occurred after therapy suspension.

Resistance Exercise Combined with Growth Hormone Augments Growth Parameters in a Male Adolescent with Cystic Fibrosis

In adolescents with cystic fibrosis (CF) the anabolic benefits of resistance exercise (RT) on skeletal muscle hypertrophy may synergize with recombinant human growth hormone (rhGH) therapy exerting an effect greater than either alone. We present a male adolescent with CF taking rhGH, who began RT. During rhGH alone, weight, height and BMI increased 14, 12 and 10 centiles (21st, 21st, 26th), respectively. When combined with RT, BMI, height and weight rose to the 48%, 47%, and 41%, respectively. While a single experience, combining RT with rhGH treatment may promote overall health improvement beyond that expected in adolescent males with CF on rhGH.

Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome.

PurposeNoonan syndrome (NS) is characterized by short stature, heart anomalies, developmental delays, dysmorphic features, cryptorchidism, and coagulation defects. Several studies reported the short-term effects of recombinant human growth hormone (rhGH) treatment on the improvement of height. This study was performed to evaluate the long-term efficacy of rhGH in children with NS in Korea.MethodsThis study included 15 prepubertal NS children who received rhGH subcutaneously at a dose of 50–75 µg/kg/day for 6 days a week for at least >3 years. Preand posttreatment data, such as height, weight, bone age, insulin-like growth factor 1 (IGF-1), and IGF binding protein 3 (IGFBP-3) levels, were collected every 6 months.ResultsChronologic age and bone age at the start of treatment were 7.97±1.81 and 5.09±2.12 years, respectively. Height standard deviation score (SDS) was increased from –2.64±0.64 to –1.54±1.24 years after 3 years (P<0.001). Serum IGF-1 SDS levels were elevated from –1.28±1.03 to –0.10±0.94 (P<0.001). Height SDS was more increased in subjects without PTPN11 mutations compared to those with mutations after 3 years (P=0.012). However, the other parameters, including bone age, IGF-1 SDS, and IGFBP-3 SDS, were not significantly different between patients with and without PTPN11 mutations.ConclusionAlthough this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies. However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway. Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations.

HGHT for Pediatric CI Recipients?

Figure.The use of human growth hormone therapy (hGHT) has increased substantially in recent years, particularly following the FDA addition of idiopathic short stature as an approved indication for hGHT. Although no studies have shown an effect of hGHT on hearing loss in general, we studied the effects of hGHT on two of our pediatric cochlear implant recipients. The first patient, S1, was diagnosed with a bilateral profound sensorineural hearing loss shortly after birth. He received his first implant in the right ear at 10 months and in the left ear at 4 years. When he was 8 years old, his pediatrician began hGHT (Norditropin) because of his unexpectedly poor growth rate, which was based on predictions from parental height. Following four months of hGHT, S1’s speech recognition scores initially decreased from 90 percent to 72 percent in the right ear, while remaining stable at 40 percent in the left ear. Despite attempts to alter programming, work with hardware, and perform other troubleshooting, there was a further decrease in performance to 52 percent in the right ear and 28 percent in the left ear. Because no reasons were identified for the decline, the parents and pediatrician, in conjunction with the cochlear implant team, decided to stop hGHT. This led to an initial increase in word recognition scores to 74 percent in the right ear and 68 percent in the left ear. The decision was then made not to resume hGHT until S1 reached the age of 12 years, when it was noted that he was still short in stature. Testing was done prior to the administration of the drug; a score of 80 percent was obtained in the right ear and 68 percent in the left ear. S1 was closely monitored for any changes in hearing, and after two months, the scores dropped to 52 percent in the right ear and 26 percent in the left ear. S1 is still receiving hGHT and continues to be closely monitored for hearing changes. The second patient, S2, was diagnosed at birth with bilateral severe sensorineural hearing loss and benefited from hearing aids until the age of 8, at which time she received a cochlear implant in the left ear while continuing to use a hearing aid in the right ear. When she was 11 years old, the parents and pediatrician noted that S2 was short for her age, and she was put on a hGHT regimen. After several months, her word recognition scores decreased from 92 percent to 82 percent. Because S2 did not notice a big difference, hGHT was continued, but the parents decided to stop therapy after one year. Subsequently, S2’s word recognition score increased to 90 percent. Even though the decrease in performance for S2 was not as dramatic as that seen by S1, no other explanation for the decrease was found. At this time, there is no known explanation why hGH has a negative effect on speech understanding with a cochlear implant. It is possible that the drug might cause an inflammatory reaction or other response that affects the transmission of the electrical signal, but the fundamental explanation is still unknown and requires further research. It is reasonable to closely monitor speech perception scores in children who undergo hGHT after receiving cochlear implants, however, because we have shown there is a possibility that hGHT can negatively affect performance with a cochlear implant and because the use of hGHT has increased.

Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.

The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.

Growth hormone therapy in children with CKD after more than two decades of practice.

This review focuses on the evidence for the efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with all stages of chronic kidney disease (CKD) and at all ages. It describes the improving height prognosis for our patients both with and without rhGH; explains the underlying hormonal abnormalities that provide the rationale for rhGH use in CKD and the endocrine changes that accompany treatment; and views on who warrants treatment, with what dose, and how long for.

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.

Recovery of Central Fever after GH Therapy in a Patient with GH Deficiency Secondary to Posttraumatic Brain Injury

Growth hormone (GH) deficiency is the most common pituitary hormone deficiency after traumatic brain injury. Patients with GH deficiency have a reduced sweating capacity which increases the risk of developing hyperthermia. To the best of our knowledge, central fever that developed due to GH deficiency and improved with GH treatment has not yet been reported. In this article, we present a case of dramatic improvement of central fever with recombinant human GH therapy in a patient with posttraumatic GH deficiency.

Analysis of the clinical and molecular characteristics of a child with achondroplasia: A case report.

Achondroplasia (ACH) is a hereditary dwarfism caused by the disturbed proliferation and differentiation of growth plate chondrocytes, followed by impaired endochondral bone growth. ACH is caused by mutations in the gene encoding the transmembrane receptor, fibroblast growth factor receptor 3 (FGFR3). In total, >90% of patients with ACH have a G1138A mutation in the transmembrane domain of the FGFR3 gene. Patients with ACH usually have no growth hormone (GH) deficiency. The current study presents the case of a four-year-old male with clinical manifestations suggestive of ACH, including a large head, prominent forehead, short upper arms and legs, and short hands with fingers assuming a trident position. The patient showed normal responses to GH provocation tests with L-dopa (peak GH concentration, 42.38 ng/ml) and insulin (peak GH concentration, 23.29 ng/ml during hypoglycemia), but a blunted response to a GH provocation test with arginine (peak GH concentration, 7.31 ng/ml). Furthermore, the GH concentration during exercise was low (4.8 ng/ml). Magnetic resonance imaging revealed a decreased pituitary volume. Thyroid function tests and the levels of sex hormones (follicle stimulating hormone, luteinizing hormone, estradiol, prolactin and progesterone), cortisol and adrenocorticotropic hormone were normal. A heterozygous G1138A mutation within the FGFR3 gene was detected, confirming the diagnosis of ACH. Thus, recombinant human GH therapy (0.1 IU/kg/day) was initiated. At the six-month follow-up, the height, arm span-to-height ratio and lower limb length-to-height ratio of the patient had increased, while the head circumference had decreased. The present results corroborate the finding that the G1138A mutation within FGFR3 is the most common ACH-causing mutation in different populations. GH may be beneficial in the treatment of short stature in ACH patients with subnormal GH secretion.

Increased height standard deviation scores in response to growth hormone therapy to near-adult height in older children with delayed skeletal maturation: results from the ANSWER Program.

BackgroundA primary goal of recombinant human growth hormone therapy (GHT) in children is attaining normal adult height. In this study, children with growth hormone deficiency (GHD) (including isolated idiopathic growth hormone deficiency [IGHD] and multiple pituitary hormone deficiency [MPHD]), idiopathic short stature (ISS), and Turner syndrome (TS) were evaluated for near-adult height (NAH) and percent achieving NAH within the normal range after approximately 4 years of GHT.MethodsData from the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program were analyzed for NAH from age at treatment start (ATS) (i.e., referral age as defined by age at enrollment in the study) to last clinic visit using one of the following two criteria: 1) age ≥18 years, or 2) if male: ≥16 years and height velocity (HV) <2 cm/year; if female: ≥15 years and HV <2 cm/year. All patients had a baseline height standard deviation score (HSDS) ≤ -2, and either GHD (n = 201), ISS (n = 19), or TS (n = 41). The main outcome measures included HSDS and corrected HSDS (HSDS-target HSDS) in response to GH treatment, and correlation of ATS with NAH HSDS.ResultsMean (± SD) chronological and bone ages at baseline were 14.0 ± 2.1 years and 11.7 ± 2.0 years, respectively, and mean GHT duration was 4.0 ± 1.6 years. Mean HSDS (baseline to NAH; GHD: -2.7 to -1.0; ISS: -2.8 to -1.4; TS: -3.0 to -1.8) and mean corrected HSDS (baseline to NAH; GHD: -2.1 to -0.3; ISS: -2.1 to -0.6; TS: -1.8 to -0.6) increased across diagnostic indications. Percentages of patients reaching near-adult HSDS > -2 were GHD: 87.6%; ISS: 78.9%; TS: 65.8%. Significant negative correlations were found between ATS and NAH HSDS when analyzed by sex.ConclusionsDespite a relatively advanced childhood age, the majority of GH-treated patients attained mean near-adult HSDS within the normal range (HSDS > -2). Negative correlations of ATS with near-adult HSDS indicate that an earlier age at treatment start would likely have resulted in greater adult height achieved in both male and female patients.

Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study.

The objective of this study was to investigate changes in the hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone (rhGH) therapy. Subjects included children with growth hormone deficiency (GHD). We conducted a multicenter, retrospective study that assessed 72 GHD patients treated with rhGH during 6 months. Patients were classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated at baseline and every 3 months. In the MPHD group, 32 patients had adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR levels. In the IGHD group, COR levels also decreased, but remained within the normal range. During rhGH therapy, COR levels were reduced, particularly in patients with MPHD. HPA axis should be monitored during rhGH therapy.

Efficacy and Safety of Growth Hormone Treatment in Children with Hypochondroplasia: Comparison with an Historical Cohort

Background/Aims: Hypochondroplasia (HCH) is a skeletal dysplasia characterized by disproportionate short stature. The aims of the study are to evaluate efficacy and safety of recombinant human growth hormone (r-hGH) therapy in HCH children, when compared with a historical cohort of untreated HCH children. Methods: Nineteen HCH patients with an initial height standard deviation score (SDS) ≤-2 and a mean age of 9.3 ± 3.1 years were treated with a mean r-hGH dose of 0.053 mg/kg/day over 3 years. Growth charts were derived from the historical cohort (n = 40). Results: Height gain in the treated population was +0.62 ± 0.81 SDS greater than in the general population, and +1.39 ± 0.9 SDS greater than in the historical untreated HCH cohort (mean gain of 7.4 ± 6.6 cm gain). A negative correlation between height gain and age at treatment initiation was reported (p = 0.04). There was no significant difference in response between patients with fibroblast growth factor receptor 3 mutations and those without. No treatment-related serious adverse events were reported. Conclusions: r-hGH treatment is well tolerated and effective in improving growth in HCH patients, particularly when started early. The treatment effect varies greatly and must be evaluated for each patient during treatment to determine the value of continued therapy.

Application of recombinant human growth hormone in improving difficult weaning

Objective To observe the applicated value of recombinant human growth hormone （ r-hGH） ther-apy in improving difficult weaning .Methods 40 patients with difficult weaning were randomly divided into the treat-ment group （20 cases） and control group （20 cases）.The control group received routine ICU treatment .The treat-ment group was given the conventional treatment and subcutaneous injection of r -hGH 8IU,1 time a day,a total of 14 days.The serum total protein,albumin,oxygenation index,peak of blood glucose,independent tidal volume changes were observed before and after treatment , the success rate and mortality rate were compared .Results After treat-ment,the total protein,albumin,tidal volume of the treatment group were （68.1 ±13.4） g/L,（40.8 ±6.0） g/L, （432 ±57）mL,which were significantly higher than those before treatment [（52.3 ±12.5）g/L,（28.4 ±4.5）g/L, （278 ±54）mL]（t=3.856,7.394,8.771,all P〈0.05）.While after treatment,the total protein,albumin,tidal vol-ume in the control group were （58.4 ±14.2）g/L,（31.0 ±5.8）g/L,（398 ±48）mL,compared with before treatment （53.2 ±13.3）g/L,（28.1 ±4.2）g/L,（271 ±49）mL,the differences were not statistically significant （all P〉0.05）.The success rate was 85% in the treatment group,which was higher than 50% in the control group（χ2 =4.103,P〈0.05）.In the treatment group,3 cases died,in the control group 9 cases died,there was statistically signif-icant difference between the two groups （χ2 =4.286,P〈0.05）.Conclusion r-hGH can improve the nutritional sta-tus of critically ill patients ,increase the strength of the respiratory muscles ,improve lung function ,help to improve the weaning rate . Key words: Human growth hormone; Ventilators, mechanical