BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growt...BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.展开更多
Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)...Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)Silk MN)based on silk protein for sustained release of recombinant human growth hormone(rhGH).Silk protein,as a friendly carrier material for proteins,could be constructed in mild full-water conditions and ensure the activity of rhGH.After manually pressing PAA/NaHCO_(3)^(-)Silk MN patch to skin for 1 min,active separation is achieved by absorbing the interstitial fluid(ISF)to trigger HCO_(3)^(-)in the active backing layer to produce carbon dioxide gas(CO_(2)).In rats,the MN patch could maintain the sustained release of rhGH for more than 7 days,and produce similar effects as daily subcutaneous(S.C.)injections of rhGH in promoting height and weight with well tolerated.Moreover,the PAA/NaHCO_(3)^(-)Silk MN patch with the potential of painless self-administration,does not require cold chain transportation and storage possess great economic benefits.Overall,the PAA/NaHCO_(3)^(-)Silk MN patch can significantly improve patient compliance and increase the availability of drugs,meet current unmet clinical needs,improve clinical treatment effects of GHD patients.展开更多
Recombinant human growth hormone(rhGH)has been widely used in the clinical treatment of growth hormone deficiency.To simplify the injection process and increase drug compliance,application of the GH injection has becom...Recombinant human growth hormone(rhGH)has been widely used in the clinical treatment of growth hormone deficiency.To simplify the injection process and increase drug compliance,application of the GH injection has become a new treatment plan in recent years.The purpose of the current study was to evaluate the efficacy and safety of rhGH injection for the treatment of growth hormone deficiency(GHD)in children in China.In a nationwide,noncomparative,prospective,randomized,open trial,31 children with confirmed complete GHD received subcutaneous injection of rhGH at 0.25 mg/kg$wk(0.107 IU/kg$d).The injection was given daily and the total weekly amount was separated into 6–7 injections.The patients were followed up at 3-month intervals and the treatment duration was 12 months.The height(HT),annual growth velocity(GV),mean height standard deviation score(HT SDS),blood serum insulin-like growth factor I(IGF-I),insulin-like growth factor binding protein 3(IGFBP-3),and bone maturity before and after treatment were compared,and the safety of the treatment was analyzed.The mean HT,GV,and HT SDS were increased from 109.0�14 cm,2.7�0.9 cm/yr,and–4.62�1.46 at baseline to 121.8�13.4 cm,12.9�3.3 cm/yr,and–2.47�1.86 after 12 months of treatment,respectively(P<0.001).At the same time,blood IGF-I and IGFBP-3 were increased significantly[41.27�64.43μg/L vs 159.21�167.92μg/L and 1540.00�1325.11 mg/L vs 3533.93�1413.82 mg/L,respectively(P<0.001)].The bone age assessments performed 6 and 12 months after the treatment showed that no advanced bone maturation was noted.No serious adverse events occurred during the treatment,and the drug-related adverse events were mainly decreased thyroid function.We conclude that rhGH injection is a safe and effective drug for treatment of growth hormone deficiency in children.展开更多
To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after...To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after the treatment with recombinant human growth hormone (r hGH). For comparison, 34 normal prepubertal children were also investigated. Relationship between leptin levels and body mass index (BMI) was observed at the same time. Our results showed that serum leptin level in normal prepubertal children was 1.22±0.34 ng/ml; the pretreatment serun leptin levels in GHD children was 3.08±2.41 ng/ml, which was significantly different from those 1, 3 and 6 months after GH treatment (i.e. 1.64±1.37 ng/ml,1.57±1.40 ng/ml and 1.35±0.89 ng/ml respectively) (all P <0.001). Our results suggested that r hGH has a suppressive effect on leptin expression.展开更多
Objective: Benefits of replacement therapy in growth hormone deficiency (GHD) are well documented in younger and middle-aged patients. The aim of our investigation was to prove the benefit of GH replacement for patien...Objective: Benefits of replacement therapy in growth hormone deficiency (GHD) are well documented in younger and middle-aged patients. The aim of our investigation was to prove the benefit of GH replacement for patients older than 60 years especially in terms of health-related quality of life (HRQoL) of age as well. Design: Data of 743 consecutively recruited patients (394 men, 349 women) with GHD aged 20 - 49 (n = 606) and 60 - 69 (n = 137) years enrolled from KIMS Germany (Pfizer International Metabolic Database) were compared. Treatment effects over the 12 months dose-finding and the subsequent phase up to three years were analysed using mixed models. Serum insulin-like growth factor I (IGF-I), fasting blood glucose, fasting serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) as well as body mass index (BMI) at baseline and at last visit were studied. HRQoL was assessed using the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Results: For both age groups and genders the IGF-I level and standardized IGF-I increased over the dose-finding phase. In women, the overall QoL-AGHDA score at the baseline examination was 8.7 (95% CI: 7.7 - 9.7) and decreased to 6.3 (95% CI: 5.1 - 7.6) at the end of the dose-finding phase (p < 0.001). In men, the corresponding values were 8.8 (95% CI: 7.8 - 9.8) and 6.4 (95% CI: 5.1 - 7.6;p < 0.001) without differences between the age groups. The therapy benefit for elderly was supported by the non-impairment after the dose-finding phase. In total cholesterol, LDL-C and fasting blood glucose, no significant changes were detected, whereas an increase in BMI did not differ between age groups. Conclusion: We could show positive effects of GH replacement on HRQoL in patients older than 60 years of age. Therefore, GH replacement should be considered in elderly GHD adults without difference compared to younger age groups.展开更多
文摘BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.
基金financial support from the National Natural Science Foundation of China(32071342 and 31922042)Guangdong Special Support Program(2019TQ05Y209)+2 种基金the Natural Science Foundation of Guangdong Province(2021A1515010431)the Fundamental Research Funds for the Central Universities(Nos.2021-RC310-005,2020-RC320-002 and 2019PT320028)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-058)。
文摘Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)Silk MN)based on silk protein for sustained release of recombinant human growth hormone(rhGH).Silk protein,as a friendly carrier material for proteins,could be constructed in mild full-water conditions and ensure the activity of rhGH.After manually pressing PAA/NaHCO_(3)^(-)Silk MN patch to skin for 1 min,active separation is achieved by absorbing the interstitial fluid(ISF)to trigger HCO_(3)^(-)in the active backing layer to produce carbon dioxide gas(CO_(2)).In rats,the MN patch could maintain the sustained release of rhGH for more than 7 days,and produce similar effects as daily subcutaneous(S.C.)injections of rhGH in promoting height and weight with well tolerated.Moreover,the PAA/NaHCO_(3)^(-)Silk MN patch with the potential of painless self-administration,does not require cold chain transportation and storage possess great economic benefits.Overall,the PAA/NaHCO_(3)^(-)Silk MN patch can significantly improve patient compliance and increase the availability of drugs,meet current unmet clinical needs,improve clinical treatment effects of GHD patients.
基金supported by the Key Construction Project of Clinical Discipline of Ministry of Health of the People’s Republic of China(No.[2007]353)the National Science&Technology Pillar Program in the Eleventh Five-Year Plan Period(No.2006 BA105A07).
文摘Recombinant human growth hormone(rhGH)has been widely used in the clinical treatment of growth hormone deficiency.To simplify the injection process and increase drug compliance,application of the GH injection has become a new treatment plan in recent years.The purpose of the current study was to evaluate the efficacy and safety of rhGH injection for the treatment of growth hormone deficiency(GHD)in children in China.In a nationwide,noncomparative,prospective,randomized,open trial,31 children with confirmed complete GHD received subcutaneous injection of rhGH at 0.25 mg/kg$wk(0.107 IU/kg$d).The injection was given daily and the total weekly amount was separated into 6–7 injections.The patients were followed up at 3-month intervals and the treatment duration was 12 months.The height(HT),annual growth velocity(GV),mean height standard deviation score(HT SDS),blood serum insulin-like growth factor I(IGF-I),insulin-like growth factor binding protein 3(IGFBP-3),and bone maturity before and after treatment were compared,and the safety of the treatment was analyzed.The mean HT,GV,and HT SDS were increased from 109.0�14 cm,2.7�0.9 cm/yr,and–4.62�1.46 at baseline to 121.8�13.4 cm,12.9�3.3 cm/yr,and–2.47�1.86 after 12 months of treatment,respectively(P<0.001).At the same time,blood IGF-I and IGFBP-3 were increased significantly[41.27�64.43μg/L vs 159.21�167.92μg/L and 1540.00�1325.11 mg/L vs 3533.93�1413.82 mg/L,respectively(P<0.001)].The bone age assessments performed 6 and 12 months after the treatment showed that no advanced bone maturation was noted.No serious adverse events occurred during the treatment,and the drug-related adverse events were mainly decreased thyroid function.We conclude that rhGH injection is a safe and effective drug for treatment of growth hormone deficiency in children.
文摘To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after the treatment with recombinant human growth hormone (r hGH). For comparison, 34 normal prepubertal children were also investigated. Relationship between leptin levels and body mass index (BMI) was observed at the same time. Our results showed that serum leptin level in normal prepubertal children was 1.22±0.34 ng/ml; the pretreatment serun leptin levels in GHD children was 3.08±2.41 ng/ml, which was significantly different from those 1, 3 and 6 months after GH treatment (i.e. 1.64±1.37 ng/ml,1.57±1.40 ng/ml and 1.35±0.89 ng/ml respectively) (all P <0.001). Our results suggested that r hGH has a suppressive effect on leptin expression.
文摘Objective: Benefits of replacement therapy in growth hormone deficiency (GHD) are well documented in younger and middle-aged patients. The aim of our investigation was to prove the benefit of GH replacement for patients older than 60 years especially in terms of health-related quality of life (HRQoL) of age as well. Design: Data of 743 consecutively recruited patients (394 men, 349 women) with GHD aged 20 - 49 (n = 606) and 60 - 69 (n = 137) years enrolled from KIMS Germany (Pfizer International Metabolic Database) were compared. Treatment effects over the 12 months dose-finding and the subsequent phase up to three years were analysed using mixed models. Serum insulin-like growth factor I (IGF-I), fasting blood glucose, fasting serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) as well as body mass index (BMI) at baseline and at last visit were studied. HRQoL was assessed using the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Results: For both age groups and genders the IGF-I level and standardized IGF-I increased over the dose-finding phase. In women, the overall QoL-AGHDA score at the baseline examination was 8.7 (95% CI: 7.7 - 9.7) and decreased to 6.3 (95% CI: 5.1 - 7.6) at the end of the dose-finding phase (p < 0.001). In men, the corresponding values were 8.8 (95% CI: 7.8 - 9.8) and 6.4 (95% CI: 5.1 - 7.6;p < 0.001) without differences between the age groups. The therapy benefit for elderly was supported by the non-impairment after the dose-finding phase. In total cholesterol, LDL-C and fasting blood glucose, no significant changes were detected, whereas an increase in BMI did not differ between age groups. Conclusion: We could show positive effects of GH replacement on HRQoL in patients older than 60 years of age. Therefore, GH replacement should be considered in elderly GHD adults without difference compared to younger age groups.
