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Abstract Objective: The main growth hormone action is to promote linear growth increasing protein synthesis stimulation and osteoblastic activity. Peak bone mass extends from adolescence to 30 years of age. Several factors may influence this acquisition and prevent fracture risk in adulthood, such as genetic potential, GH, ethnicity, and lifestyle factors. This study aims to compare bone mass and osteometabolic profile of white and Afro-descendant Brazilian adolescents in the transition phase, who were treated with human recombinant growth hormone in childhood. Methods: The authors selected 38 adolescents from the Transition Outpatient Clinic of the University of São Paulo. Lumbar spine and total body bone mineral density (BMD) and bone mineral content (BMC), serum calcium, 25-OH-vitamin D and bone markers were analyzed at the rhGH withdrawal. Results: The mean age was 16.8 ± 1.6 years. There were 21 Afro-descendant and 17 whites. Thirty-four percent of the sample presented vitamin D insufficiency, 66% inadequate calcium intake and 44.7% physical inactivity. The Afro-descendants showed a lower lumbar spine and total body Z scores than those of the whites (p = 0.04 and p = 0.03, respectively), as well as their mean body weight (p = 0.03). There were no differences in the remaining osteometabolic parameters. Conclusion: As most adolescents had vitamin D insufficiency, low calcium intake, and physical inactivity, calcium, and cholecalciferol supplementation and lifestyle changes should be encouraged. The Brazilian Afro-descendant may be a vulnerable group for low bone mass, requiring
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@#Objective To optimize and verify the size exclusion chromatography-high performance liquid chromatography(SEC-HPLC) method for the determination of recombinant human growth hormone(rhGH)-Fc immunofusion protein polymer.Methods The multimer content of rhGH-Fc immunofusion protein was detected by SEC-HPLC.The detection conditions(salt concentration,mobile phase pH,flow rate,column temperature and column model) were optimized to observe the separation effect of the target proteins and polymers.The system suitability,specificity,linearity and range,precision,accuracy and limit of quantification of the method were verified.Results The optimized method was to use TSK-gel G2000SW_(x1)column(5 μm,7.8 mm × 300 mm),mobile phase of 50 mmol/L phosphate buffer(pH 6.80),detection wavelength of280 nm,injection volume of 100 μL,flow rate of 0.6 mL/min and column temperature of 45 ℃.The resolution of rhGHFc immunofusion protein and polymer,the theoretical plate number and the tailing factor all met the requirements;the peak time of rhGH-Fc immunofusion protein was the same as that of the control,while the peak time of GH national standard was different from that of the control,and the protein buffer showed no peak;the concentration of rhGH-Fc immunofusion protein was in the range of 0.307～1.842 mg/mL with good linear correlation between the peak area integral value and the injection volume(R~2=0.999 4);the RSD of peak area and purity in repeatability verification were 0.7% and 0.1%,respectively;the RSD of intermediate precision verification was 0.8%;the average recovery rate of accuracy verification was 99.1% with the RSD of 1.9%;the limit of quantification was 6 μg/mL.Conclusion The optimized SEC-HPLC method was used to detect the content of polymer in rhGH-Fc immunofusion protein with improved accuracy,and the column efficiency and separation were in accordance with the relevant requirements of Chinese Pharmacopoeia(Volume Ⅳ,2020edition),which could be used for the detection of polymer content in samples.
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@#Objective To develop and verify a whole-column image capillary isoelectric focusing(iCIEF) electrophoresis method to analyze the charge heterogeneity of recombinant human growth hormone Fc fusion protein(Fc-rhGH).Methods The iCIEF analysis method of Fc-rhGH was developed by optimizing the target protein concentration,cosolvent(urea)concentration and focusing time.The target protein was simultaneously analyzed by this method and traditional flat plate isoelectric focusing(IEF) electrophoresis,and the results were compared;The specificity,accuracy,precision,limit of quantitation(LOQ) and durability of the developed method were verified.Results The optimized method was using the mixed solution of 8 mol/L urea,0.35% methyl cellulose(MC),4% amphoteric electrolyte and 0.5% isoelectric point marker as the sample buffer,and the focusing condition was 1 500 V 1 min,3 000 V 5.5 min.IEF was not suitable for analyzing the charge heterogeneity of Fc-rhGH solution.Using the optimized iCIEF for analysis,the target protein was significantly different from the unrelated protein,and the baseline of blank reagent was stable;The recovery rate of accuracy verification was within 90%～110%,and the linear range was 0.25～0.75 mg/mL(50%～150% of the target loading volume);The RSD of each isomer pI in the repeatability verification was less than 0.3%,and the RSD of peak area percentage was less than 5%;The LOQ was 0.04 mg/ml.The sample storage time durability,amphoteric electrolyte pharmalyte 3-10 durability and MC durability of this method were good.Using this method to analyze the charge heterogeneity of Fc-rhGH physicochemical reference substance,eight charge heterogeneities of the reference substance were effectively separated,and the pI ranged from 5.9 to 6.4.Conclusion The developed iCIEF method had good specificity,accuracy,precision and durability,and was more suitable for efficient analysis of charge heterogeneity of Fc-rhGH than traditional flat plate IEF,which was of great significance for the quality control of Fc-rhGH and other Fc fusion proteins.
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@#ObjectiveTo optimize the condition for anion exchange chromatography in purification process of recombinant human growth hormone-Fc(rhGH-Fc)fusion protein by Design of Experiment(DOE)so as to decrease the content of host cell protein(HCP)in bulk of protein.MethodsA complete factorial experimental design with four factors at two levels was established by the DOE in Minitab 19 software.The condition(flow rate,sample load,pH value of buffer and salt concentration of eluent)for anion exchange chromatography in purification process of rhGH-Fc was optimized by DOE to find out the operating space.ResultsThe experimental results were predicted accurately by the established DOE model.The sample load,pH value of buffer,salt concentration of eluent as well as the interaction of pH value of buffer and salt concentration of eluent showed significant influence on the HCP content in the harvest.The optimal sample load,flow rate as well as pH value and salt concentration of eluent were 15 mg/mL,120 cm/h,7.0 ～ 8.0 and 0.1 mol/L respectively.The HCP contents in eluents under the optimal condition were less than 400 ng/mg,which met the requirements for verification within the range of results in determined operating space.ConclusionThe condition for removal of HCP by anion exchange chromatography was successfully optimized by DOE,which provided a reference for further application of DOE in the biopharmaceutical field.
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@#Objective To optimize the expression of recombinant human growth hormone-Fc(rhGH-Fc)fusion protein in CHO cells in order to obtain better glycosylation ratio and lower content of highmannose.Methods CHO cells expressing rhGH-Fc were cultured in a 7 L bioreactor.The glycosylation modifications of rhGH-Fc were adjusted by improving the composition of feeding media(using three commercial media:Gly-1:EX-CELL Glycosylation Adjust,Gly-2:SHEFF-CHO PLUS PG ACF and Gly-3:EfficientFeed C + AGT Supplement & GlycanTune C + Total Feed),and the glycosylation type and proportion of the target proteins were analyzed by mass spectrometry.Results The G0F(main glycosylation types:G0,G1 and G2;F:fucose)of Gly-1,Gly-2 and Gly-3 were 32.89%,58.66% and 33.28%,the G1F were 31.39%,18.03%and 34.90%,and the G2F were 31.39%,18.03% and 34.90%,respectively.Gly-1 and Gly-3 made the target protein contain less G0F while more G2F;Gly-3 feeding scheme-showed less high mannose modification than the other two schemes.Conclusion Gly-1 medium changed the glycosylation modification from G0F to G1F and G2F,while Gly-2 medium changed that from G2F and G1F to G0F.However,Gly-3 medium changed the glycosylation modification from G0F to G1F and G2F,and the contentof high mannose was less than 5%,which may have a better effect on modifying glycosylation type and proportion of the target protein.
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Noonan syndrome(NS)is an inherited disease involving multiple systems.The main clinical manifestations include distinctive facial features, short stature, heart defects, developmental delay and chest deformity.Short stature, reported in up to 70% of NS patients, is one of the main reasons NS patients seek medical treatment.The pathogenesis is associated with the up-regulation of RAS-mitogen activated protein kinase(RAS-MAPK)signal pathway.Further study is needed for some further specific mechanisms.Recombinant human growth hormone(rhGH)therapy has been approved for NS patients with short stature and has achieved a good therapeutic effect.However, the knowledge of drug dosage, influencing factors, long-term efficacy and risk of rhGH treatment is still insufficient.This paper reviews the pathogenesis and treatment of short stature in NS, providing help for the treatment and management of the disease.
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In this study, we established a novel bioassay to determine the activity of polyethylene glycolated recombinant human growth hormone (PEG-rhGH) using Nb2-11 cells. We performed experimental condition optimization and methodological verification, and then detected the relative potency of PEG-rhGH products using this method. We demonstrated that the bioactivity of PEG-rhGH in promoting Nb2-11 cell proliferation displays a dose-response relationship, which conformed to the four-parameter model. Using PEG-rhGH reference as a control, we analyzed the relative potency of six batches of PEG-rhGH products, as well as linearity, regression and parallelism of the obtained curves. The relative potency of six batches of PEG-rhGH products was 95% to 105%. These results implied that the new bioassay established may be employed in quality control of PEG-rhGH products.
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Clinical data of a child with acromesomelic dysplasia Maroteaux type (AMDM) treated in the Department of Pediatrics, Tianjin Medical University General Hospital at November 2018 was retrospectively analyzed.The female child aged 3 years and 3 months old with 83 cm height (-3.84 SD) had clinical manifestations of disproportionate short stature, disproportionate shortening of forearms and forelegs, and stubby fingers and toes.Gene sequencing identified compound heterozygous mutations, c.1640T>A(p.Val547Asp)/c.682G>A(p.Gly228Ser), in the NPR2 gene, which have not been reported in the Human Gene Mutation Database.Their protein function was predicted harmful.The child was diagnosed as AMDM.During the follow-up until 4 years and 8 months old, the child was 90 cm tall (-4.35 SD), with a growth velocity of 4.9 cm/year.She was treated with recombinant human growth hormone (rhGH) treatment for 9 months and regularly followed up.The child was now 98.2 cm height (-3.07 SD) and she had a growth velocity of 10.9 cm/year.This case report enriched the gene mutation spectrum of AMDM.Treatment with rhGH can effectively improve the height of the child, but the long-term effect needs further follow-up and observation.
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Objective:To analyze the genetic etiology of idiopathic short stature(ISS) children, and to investigate the clinical characteristics of Noonan syndrome caused by PTPN11 gene mutation, and the response to recombinant human growth hormone(rhGH) as well.Methods:Genomic DNA was extracted from the peripheral blood of 232 ISS patients, and the genome was detected by whole exon sequencing. The gene variation was analyzed according to the guideline of American College of Medical Genetics and Genomics(ACMG), and clinical baseline data and follow-up data of rhGH treatment were collected from PTPN11 gene pathogenic patients.Results:Among 232 ISS patients, 6 were found to have PTPN11 pathogenic gene variants(c.1507G>C, c. 317A>G, c. 923A>G, c. 922A>G, c. 236A>G, c. 922A>G), diagnosed as Noonan syndrome. Together with 3 cases of Noonan syndrome patients(all PTPN11 gene variation C. 1510A>G) previously diagnosed in our hospital, the clinical characteristics of patients were analyzed. Among the 9 Noonan syndrome patients, 7 were boys and 2 were girls. The average age was 10.2(4.5, 14.7) years old, and their height standard deviation score was -3.06 SD(95% CI -2.29 SD--3.94 SD). Among them, 4 patients received rhGH treatment with an average treatment duration of 2.25(1.5, 3.5) years. After treatment, their height increased by 14.3(8.6, 23.9) cm, and the change in height standard deviation score improved by 0.21 SD(95% CI 0.12 SD-0.27 SD). Conclusion:Noonan syndrome has a wide range of clinical phenotypes. For children with short stature, heart defects and cryptorchidism, the possibility of Noonan syndrome should be considered. PTPN11 is the common pathogenic gene for Noonan syndrome, and genetic testing facilitates the early diagnosis, treatment, and follow-up prognosis of Noonan syndrome patients.
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@#AIM:To explore the effects of recombinant human growth hormone(rHGH)on early rehabilitation in rabbit corneal epithelial wound. <p>METHODS:Thirty-two New Zealand rabbits were selected to establish the corneal epithelial defects models. One eye was treated with normal saline(NC group)and the other eye was treated with 20nmol/L rHGH(rHGH group)in a randomized double-blinded way. The corneal healing process was monitored by the corneal fluorescein staining scores at 0h, 24h, 48h, and 72h after the surgery. The central corneal sensitivity was detected by Cochet-Bonnet corneal esthesiometer and the concentrations of inflammatory mediators interlecukin-1α(IL-1α), interlecukin-17(IL-17), interlecukin-21(IL-21), Leptin, matrix metalloproteinase-9(MMP-9)and tumor necrosis factor-α(TNF-α)in collected tears were measured by multiplex antibody microarray. <p>RESULTS: The corneal epithelial healing rates of the NC group and rHGH group were(62.52±6.73)% and(79.62±10.62)%(<i>P</i><0.05),(90.56±9.57)% and(98.43±3.65)%(<i>P</i><0.05)at 48h and 72h postoperatively. The central corneal sensitivity of rHGH group(4.22±0.26)cm was better than that in NC group(3.22±0.42)cm at 48h after surgery(<i>P</i><0.05). The expressions of TNF-α and IL-1α increased in both groups at each time point after operation, and the expressions in NC group were higher than those in the rHGH group. Both groups had higher MMP-9 concentrations in the tear fluid at 24 and 48h postoperation in comparison with the point before the operation. The MMP-9 expression in NC group was higher than that in the rHGH group at 48h postoperatively. The expressions of IL-21 in NC group were higher than those in the rHGH group at 24 and 48h postoperation in comparison with the point before the operation(<i>P</i><0.05). No significant differences in tearIL-17 and Leptin were observed between groups before and after surgery(<i>P</i>>0.05).<p>CONCLUSION: Topical application of rHGH can accelerate the early stage of rabbit corneal epithelial wound healing <i>in vivo</i>.
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ABSTRACT Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7
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Humans , Child , Adult , Human Growth Hormone/administration & dosage , Growth Disorders/drug therapy , Drug Administration Schedule , Drug Design , Chemistry, Pharmaceutical , Human Growth Hormone/pharmacokinetics , Human Growth Hormone/chemistry , Delayed-Action PreparationsABSTRACT
El síndrome de Turner (ST) afecta a uno de cada 2000-2500 recién nacidos vivos y tiene una prevalencia de 50 por cada 100 000 mujeres. Las manifestaciones clínicas son variables, dependiendo del tipo de alteración cromosómica y de la edad de presentación. Una de las características más prevalentes y sobresalientes del síndrome es su estatura extremadamente baja. La hormona de crecimiento humana recombinante (rh-GH) se ha usado para aumentar el crecimiento y la estatura final en las niñas que tienen el síndrome de Turner. Para valorar los efectos de la hormona de crecimiento recombinante en las niñas y adolescentes con ST, hemos tomado en cuenta el efecto de la hGH, considerando la velocidad en la talla de crecimiento como un punto importante del estudio observacional retrospectivo. Resultados principales: El uso de rh-GH tiene una relación estadísticamente significativa (p0.049 <0.05), que se asocia con un factor de influencia positiva en relación con la velocidad de crecimiento, como variable principal. Al comparar a las pacientes que recibieron la hormona de crecimiento con las que no la recibieron, en las primeras existe la tendencia a acercarse a la curva del percentil 10 en comparación con la de aquellas que no recibieron la rh-GH, que estuvieron más lejos de la curva.
Turner syndrome (TS) affects about one in 1500 to 2500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Recombinant human growth hormone (rh-GH) has been used to increase growth and final height in girls who have Turner syndrome. To assess the effects of recombinant growth hormone in children and adolescents with TS we have evaluated the effect of HGH considering growth rate as an important point through a retrospective observational study. Main results: The use of rh-GH has a statistically significant relationship (p0.049 <0.05) that is associated with an influencing factor in favor of the use of rh-GH in relation to the variable growth rate. When comparing the patients who received growth hormone with those who did not receive, there is the tendency to arrive closer to the 10th percentile curve compared to the curve of the patients who did not receive rh-GH, which is further away.
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Humans , Female , Child , Adolescent , Turner Syndrome , Growth Hormone , Growth , Women , Body Height , ChromosomesABSTRACT
PURPOSE: To analyze the growth response to growth hormone (GH) therapy in prepubertal patients with Noonan syndrome (NS) harboring different genetic mutations. METHODS: Twenty-three patients with prepubertal NS treated at Pusan National University Children’s Hospital between March 2009 and July 2017 were enrolled. According to the disease-causing genes identified, the patients with NS were divided into 4 groups. Three groups were positive for mutations of the PTPN11, RAF1, and SOS1 genes. The five genes undetected (FGU) group was negative for PTPN11, RAF1, SOS1, KRAS, and BRAF gene mutations. The influence of genotype was retrospectively analyzed by comparing the growth parameters after GH therapy. RESULTS: The mean chronological age at the start of GH treatment was 5.85±2.67 years. At the beginning of the GH treatment, the height standard deviation score (SDS), growth velocity (GV), and lower levels of insulin-like growth factor-1 (IGF)-1 levels were not statistically different among the groups. All the 23 NS patients had significantly increased height SDS and serum IGF-1 level during the 3 years of treatment. GV was highest during the first year of treatment. During the 3 years of GH therapy, the PTPN11, RAF1, and SOS1 groups showed less improvement in height SDS, IGF-1 SDS, and GV, and less increase in bone age-to-chronological age ratio than the FGU group. CONCLUSION: The 3-year GH therapy in the 23 prepubertal patients with NS was effective in improving height SDS, GV, and serum IGF-1 levels. The FGU group showed a better response to recombinant human GH therapy than the PTPN11, RAF1, and SOS1 groups.
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Child , Humans , Genotype , Growth Hormone , Insulin-Like Growth Factor I , Noonan Syndrome , Retrospective StudiesABSTRACT
Congenital ovarian dysplasia syndrome is a feminine genetic disease which is rarely seen.Its clinical manifestations include short stature and primary ovarian insufficiency, in addition of which could cause multi-systema-tic complications.According to its therapeutic methods, recombinant human growth hormone and Estrogen are normally used to improve stature and the development of gonad.However, these methods are long-lasting and with great expense, which may result in economic and emotional burdens on patients and their family.On the contrary, individual therapies has a rather precise pharmacogenetical evaluation on patients and their disease, which could effectively decrease iatrogenic loss while enhancing the curative effect.
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Congenital ovarian dysplasia syndrome is a feminine genetic disease which is rarely seen.Its clinical manifestations include short stature and primary ovarian insufficiency,in addition of which could cause multi-systematic complications.According to its therapeutic methods,recombinant human growth hormone and Estrogen are normally used to improve stature and the development of gonad.However,these methods are long-lasting and with great expense,which may result in economic and emotional burdens on patients and their family.On the contrary,individual therapies has a rather precise pharmacogenetical evaluation on patients and their disease,which could effectively decrease iatrogenic loss while enhancing the curative effect.
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OBJECTIVE: To explore the therapeutic effects and adverse reactions of a combination treatment of recombinant human growth hormone(rh GH)with letrozole,compared with rh GH alone,in short pubertal boys. METHODS: Fifty-five short pubertal boys were divided into two groups,one group was treated with rh GH(rh GH group,n=24),and the other group was treated with the combination of rh GH and letrozole(combination group,n=31). All boys had completed the over one year of treatment. The advancement of bone age(BA),height standard deviation score by bone age(Ht SDSBA),body mass index standard deviation(BMI SDS),glucose and lipid metabolism,and the changes of the external genitalia and adverse reactions were evaluated. RESULTS: The age of two groups was(12.72±0.99)years and(12.90±1.36)years,respectively(P>0.05).The treatment periods were(1.71±0.55)years and(1.58±0.46)years,respectively(P>0.05).Their BA increased(0.96±0.27)years/year and(0.50±0.20)years/year during treatment,respectively(P0.05)respectively during treatment. There were no statistically significant difference in BMI SDS,glucose or lipid metabolism between the two groups.Three boys in combination group suffered from fractures during the treatment. Ultrasound bone density scan showed serious shortage of bone mineral density;after supplemental calcium and calcitriol,bone density increased within 3 to 6 months,and there was no recurrence of fracture. CONCLUSION: Combination of rh GH and letrozole in short pubertal boys could inhibit BA progression and ameliorate HtSDSBA,without affecting the normal sexual development,but bone density may be affected,and long-term follow-up is needed.
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This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5-3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.
Subject(s)
Child , Female , Humans , Male , Growth Disorders , Blood , Drug Therapy , Human Growth Hormone , Therapeutic Uses , Insulin-Like Growth Factor I , Metabolism , Recombinant Proteins , Therapeutic Uses , Thyrotropin , Blood , Thyroxine , BloodABSTRACT
Objective To investigate the effect of recombinant human growth hormone (rhGH) on the growth rate, glucose and lipid metabolism and bone metabolism in children with idiopathic short stature (ISS). Methods The clinical data of 150 children with ISS admitted to the hospital from January 2010 to January 2015 were collected. The children were divided into the routine group (68 patients) and rhGH group (82 patients) according to the treatment methods. The routine group was given enhanced nutritional guidance, enhanced protein and calcium intake, and guidance for exercise. On this basis, rhGH group was additionally treated with rhGH. The intervention lasted for 12 months, and changes of height, weight, bone age (BA) and growth velocity (GV) in two groups were statistically analyzed. Changes in fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and other glucose and lipid metabolism indicators before and after treatment were detected. The insulin sensitivity index (ISI) was calculated, and changes in serum insulin-like factor 1 (IGF-1), osteocalcin (OC), bone alkaline phosphatase (BAP), typeⅠprocollagen amino-terminal propeptide (PINP), β-collagen degradation products (β-CTX) and other bone metabolism parameters before and after treatment were determined. The incidence of adverse reactions in both groups was statistically analyzed. Results There were no significant differences in height, weight, BA or GV between two groups before treatment (P>0.05). After 12 months of treatment, the above indicators in both groups were increased (P<0.05). The height, weight, BA and GV were (132.12 ± 7.26) cm, (26.21 ± 1.74) kg, (9.41 ± 0.37) years old and (10.03 ± 2.41) cm/year of the rhGH group, which were significantly higher than those of the routine group [(124.22 ± 6.31) cm, (24.13 ± 1.92) kg, (8.96 ± 0.42) years old and (5.85 ± 1.76) cm/year (P<0.05)]. There were no significant differences in glucose and lipid metabolism levels between two groups before and after treatment (P>0.05). There was no statistical difference in bone metabolism indexes between two groups before treatment (P>0.05). After 12 months of treatment, PINP, IGF-1, OC and BAP in both groups increased while β-CTX decreased (P<0.05). PINP, IGF-1, OC and BAP in rhGH group [(598.21 ± 78.57) μg/L, (301.23 ± 51.45) μg/L, (78.52 ± 12.65) μg/L, (171.26 ± 42.17) U/L] were higher than those in routine group [(520.14 ± 47.55)μg/L, (244.35 ± 46.38)μg/L, (70.25 ± 9.77) μg/L, (120.55 ± 38.42) U/L] (P<0.05), whileβ-CTX was lower than that in routine group [(0.48 ± 0.26)μg/L vs (0.63 ± 0.24) μg/L] (P<0.05). There were no significant difference in adverse reaction between two groups [3.66％(3/82) vs. 0, P>0.05]. Conclusions The rhGH treatment of children with ISS can obviously promote the growth and improve bone metabolism and growth rate of children, without significant adverse effect on their glucose and lipid metabolism and with certain safety.
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Objective@#To analyze the clinical data, karyotype, growth hormone receptor (GHR) exon 3 polymorphism, etc. in Turner syndrome before and after recombinant human growth hormone (rhGH) treatment, and thereby to understand the related factors influencing the rhGH curative effect in children with Turner syndrome.@*Methods@#This was a retrospective study of 31 cases with Turner syndrome who were treated with growth hormone for more than 1 year in the pediatric outpatient department of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2010 to January 2017. The GHR Exon3 polymorphism was detected by PCR assay, Turner syndrome children were divided according to GHR exon3 genotype for homozygous for the full-length GHR isoform (fl/fl-GHR)and carriers of one or two copies of the GHR exon3 allele(fl/d3-GHR;d3/d3-GHR).According to the karyotype, the children were divided into 45,X karyotype group and other karyotype group. The height standard deviation (Ht-SDS) and growth velocity (GV) as indicators to measure rhGH treatment efficacy, the data were analyzed by the SPSS12.0 software (t test, one-way ANOVA and multiple linear regression analysis).@*Results@#(1) The mean age at diagnosis of 31 cases was (12.2±2.9) years, the bone age was (8.9±2.4) years, the height was (126.2±10.5) cm and the Ht-SDS was (-3.5±1.3) SDS. The karyotype was 45,X in 14 patients, 17 cases had other karyotypes. Thirteen cases were of (fl/fl-GHR) (42%), 14 cases of fl/d3-GHR (45%) and 4 cases of d3/d3-GHR(13%).Among the 31 cases, the main reason for 5 patients' hospitalization was no secondary sexual characteristics, another 26 cases had short stature (accounting for 81%).(2) After Growth hormone treatment, growth rate (cm/year)(7.3±1.4, 7.0±3.0, 7.0±1.3) and Ht-SDS (-2.8±1.2, -2.5±0.9, -2.2±0.8) were significantly higher than the pre-treatment levels (2.9±0.9, -3.5±1.3), the difference was statistically significant (F=54.12, 4.43, P<0.05) ; the third year Ht-SDS(-2.2±0.8)higher than the first year Ht-SDS(-2.8±1.2), the difference was statistically significant (t=-2.3, P<0.05) .(3)Before rhGH treatment, the height of 45,X karyotype group was significantly lower than that of other karyotypes ((122.1±9.1) cm vs. (129.9±10.3) cm, t=-2.2, P<0.05)). Before and after rhGH treatment, there was no significant difference in growth rate (cm/year) and Ht-SDS, between 45, X karyotype group and other karyotype group, but with the prolongation of treatment time, the Ht-SDS of other karyotype groups had an improvement trend compared with the 45,X karyotype groups. (4) After short-term and long-term treatment with rhGH, there were no significant differences in GV, Ht-SDS between patients with different genotypes (P>0.05). (5) Multivariate linear regression analysis showed that ΔHt-SDS was negatively correlated with the age at initial treatment(partial regression coefficient=-0.098, P <0.05), and positively correlated with GV before treatment(partial regression coefficient=0.202, P<0.05).@*Conclusions@#In Turner's syndrome children, the earlier the rhGH treatment started, the faster the growth rate before treatment and the longer treatment duration, the better effect of rhGH treatment was obtained. Before rhGH treatment, the height of 45,X karyotype group was significantly lower than that of other karyotypes. Before and after rhGH treatment, there was no significant difference in growth rate (cm/year) and Ht-SDS, but with the prolongation of treatment time, the Ht-SDS of other karyotype groups had an improvement trend compared with the 45,X karyotype groups. GHR exon 3 polymorphism did not significantly affect the efficacy of rhGH in Turner syndrome children, but large-scale long-term studies are still needed.
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Recombinant human growth hormone (rhGH) administration stimulate the secretion of the brain insulin-like growth factor-1 (IGF-1) concentration and IGF-1 is a pleiotropic neurotropic peptide to exert beneficial effect for the injured brain tissues. Citicoline (cytidine-59-diphosphocholine; CDP-choline) is well known to improve neurological outcome in acute stroke. This study aimed to evaluate whether rhGH can potentiate citicoline effect on functional recovery in acute stroke patient. Thirty patients were enrolled. Ten patients were treated with rhGH subcutaneous injection for 6 months on top of citicoline for 6 weeks (GH6 group), and 10 patients for 3 months (GH3 group) with 6 weeks of citicoline treatment as well, and final 10 patients only with citicoline (control group). Functional outcome was determined by Korean modified Barthel Index (K-MBI) and modified Rankin Scale (mRS) at baseline and 6 months after treatment. Seven and 4 patients withdrew from GH6 and GH3 group, respectively. Final 3 patients in GH6 group, 6 patients in GH3 group and 10 patients in control group were analyzed. The K-MBI, and mRS scores from all 3 groups increased in 6 months compared to baseline in intra-group comparison. In inter-group comparison, however, GH6 but not GH3 showed statistically significant improvement compared to control. Administration of rhGH for 6 months on top of 6-week citicoline treatment resulted in further improvement in K-MBI and mRS in acute stroke patients. Further studies in increasing injection dose or injection period is needed.