2.Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study.
Xiu-Fang WEI ; Yue-Ying ZHANG ; Zhi-Ping YAN ; Jing AN
Chinese Journal of Contemporary Pediatrics 2023;25(8):800-804
		                        		
		                        			OBJECTIVES:
		                        			To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions.
		                        		
		                        			METHODS:
		                        			A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups.
		                        		
		                        			RESULTS:
		                        			After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05).
		                        		
		                        			CONCLUSIONS
		                        			In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Body Height
		                        			;
		                        		
		                        			Human Growth Hormone/therapeutic use*
		                        			;
		                        		
		                        			Hyperplasia
		                        			;
		                        		
		                        			Insulin-Like Growth Factor Binding Protein 3
		                        			;
		                        		
		                        			Insulin-Like Growth Factor I
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Pituitary Gland/pathology*
		                        			;
		                        		
		                        			Recombinant Proteins/therapeutic use*
		                        			
		                        		
		                        	
3.Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature.
Han-Han DONG ; Meng-Meng LI ; Meng SUN ; Ran ZHOU ; Xin-Ying ZHANG ; Ya-Ying CHENG
Chinese Journal of Contemporary Pediatrics 2023;25(11):1143-1149
		                        		
		                        			OBJECTIVES:
		                        			To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children.
		                        		
		                        			METHODS:
		                        			A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes.
		                        		
		                        			RESULTS:
		                        			There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05).
		                        		
		                        			CONCLUSIONS
		                        			The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Human Growth Hormone/pharmacology*
		                        			;
		                        		
		                        			Insulin-Like Growth Factor I/pharmacology*
		                        			;
		                        		
		                        			Fibroblast Growth Factor-23
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Growth Disorders
		                        			;
		                        		
		                        			Phosphates/pharmacology*
		                        			;
		                        		
		                        			Body Height
		                        			
		                        		
		                        	
4.Diagnostic significance and considerations of growth hormone stimulation testing and insulin-like growth factor 1 in growth hormone deficiency.
Chinese Journal of Contemporary Pediatrics 2023;25(12):1193-1197
		                        		
		                        			
		                        			The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Growth Hormone/metabolism*
		                        			;
		                        		
		                        			Insulin-Like Growth Factor I/metabolism*
		                        			;
		                        		
		                        			Insulin-Like Peptides
		                        			;
		                        		
		                        			Insulin-Like Growth Factor Binding Protein 3
		                        			;
		                        		
		                        			Human Growth Hormone/metabolism*
		                        			;
		                        		
		                        			Dwarfism, Pituitary/diagnosis*
		                        			
		                        		
		                        	
5.Research advances on common detection biomarkers and methodology of children's growth and development assessment.
Chinese Journal of Preventive Medicine 2022;56(9):1211-1217
		                        		
		                        			
		                        			With the rapid dissemination of information in modern society, Chinese residents pay more attention to the scientific concept of childcare, which makes the child prevention and health care industry develop rapidly. The law of children's growth and development is extremely complex, so it is necessary to detect different biomarkers according to different growth and development evaluation angles. Human growth hormone(hGH), insulin-like growth factor-1(IGF-1), insulin-like growth factor binding protein-3(IGFBP-3), thyroid hormone, sex hormone, anti-müllerian hormone(AMH) and 25-hydroxy vitamin D(25-OH VD) are common biomarkers to monitor children's growth and development. This article aims to explain the concept and characteristics of common biomarkers of growth and development, summarize the detection methods of common biomarkers of growth and development evaluation developed in recent years, and provide a reference for children's prevention and health care to select appropriate detection biomarkers.
		                        		
		                        		
		                        		
		                        			Anti-Mullerian Hormone/metabolism*
		                        			;
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Growth and Development
		                        			;
		                        		
		                        			Human Growth Hormone/metabolism*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Insulin-Like Growth Factor Binding Protein 3
		                        			;
		                        		
		                        			Insulin-Like Growth Factor I/metabolism*
		                        			;
		                        		
		                        			Thyroid Hormones
		                        			;
		                        		
		                        			Vitamin D
		                        			
		                        		
		                        	
6.Consistency evaluation of 2 methods in detecting serum insulin-like growth factorⅠ in children.
Jia Jia CHEN ; Xin Ying GAO ; Bing Yan CAO ; Ya Guang PENG ; Chang SU ; Chun Xiu GONG
Chinese Journal of Pediatrics 2022;60(8):781-785
		                        		
		                        			
		                        			Objective: To evaluate the consistency of mass spectrometry (MS) and chemiluminescence immunoassay (CLIA) in detecting serum insulin-like growth factor-1 (IGF-1) and IGF-1 standard deviation score (SDS). Methods: This cross-sectional parallel control study prospectively collected the serum samples of 115 children with short stature disorders who were admitted in the Department of Endocrinology, Beijing Children's Hospital, Capital Medical University from February 2020 to December 2021. The serum IGF-1 level was detected by CLIA and MS, and converted to SDS for consistency analysis. Pearson analysis was used to analyze the correlation between the 2 methods, and Deming regression equation was established. Bland-Altman diagram and weighted Kappa coefficient were used to evaluate the consistency of the 2 methods. Results: There were 46 boys (40.0%) and 69 girls (60.0%), aged (8±3) years. Among the 115 cases, 37 were Turner syndrome, 59 were small for gestational age (SGA) at term, 1 was growth hormone deficiency (GHD) and 18 were other diseases. Pearson correlation analysis showed a preferable correlation between IGF-1 measured by the 2 detection methods (r=0.94, P<0.01), and IGF-1 SDS was also significantly correlated (r=0.92, P<0.01). Bland-Altman analysis showed that the consistency of serum IGF-1 levels detected by the 2 methods was poor, and the mean difference between CLIA and MS was 33.38 μg/L. The result detected by CLIA was significantly higher than that by MS, with SDS of 43.51 μg/L (95%CI -51.89-118.7 μg/L). After converting the results to SDS and removing 3 outliers (including 1 GHD patient), the weighted Kappa showed acceptable consistency (κ=0.68). Conclusion: In clinical application, after converting to IGF-1 SDS, IGF-1 detected by MS and CLIA can be used for cross-reference, but too high or too low levels should be cautious about.
		                        		
		                        		
		                        		
		                        			Body Height
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Growth Disorders/diagnosis*
		                        			;
		                        		
		                        			Human Growth Hormone
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Insulin-Like Growth Factor Binding Protein 3
		                        			;
		                        		
		                        			Insulin-Like Growth Factor I/metabolism*
		                        			;
		                        		
		                        			Insulins
		                        			;
		                        		
		                        			Male
		                        			
		                        		
		                        	
7.Efficacy of recombinant human growth hormone treatment in children born small for gestational age with syndromic and non-syndromic short stature.
Ming CHENG ; Bing Yan CAO ; Min LIU ; Chang SU ; Jia Jia CHEN ; Xiao Qiao LI ; Bei Bei ZHANG ; Yu Ting SHI ; Zi Jun HE ; Chun Xiu GONG
Chinese Journal of Pediatrics 2022;60(11):1196-1201
		                        		
		                        			
		                        			Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Body Height
		                        			;
		                        		
		                        			Gestational Age
		                        			;
		                        		
		                        			Human Growth Hormone/therapeutic use*
		                        			;
		                        		
		                        			Infant, Small for Gestational Age
		                        			;
		                        		
		                        			Insulin
		                        			;
		                        		
		                        			Insulin Resistance
		                        			;
		                        		
		                        			Recombinant Proteins
		                        			;
		                        		
		                        			Child, Preschool
		                        			
		                        		
		                        	
8.Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature.
Yuanmei KONG ; Hong CHEN ; Li LIANG ; Maoni ZHENG ; Yanlan FANG ; Chunlin WANG
Journal of Zhejiang University. Medical sciences 2020;49(3):283-290
		                        		
		                        			OBJECTIVE:
		                        			To assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature.
		                        		
		                        			METHODS:
		                        			One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group ( =108) and rhGH group ( =43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg ·d , and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored.
		                        		
		                        			RESULTS:
		                        			After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDS (height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group( < 0.05 or < 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose.
		                        		
		                        			CONCLUSIONS
		                        			AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Aromatase Inhibitors
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Body Height
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Growth Disorders
		                        			;
		                        		
		                        			Human Growth Hormone
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Recombinant Proteins
		                        			
		                        		
		                        	
10.Etiology and genetic diagnosis of short stature in children.
Wei-Wei CHEN ; Huan-Xin LIU ; Jing LIU ; Lin-Lin YANG ; Min LIU ; Hui-Juan MA
Chinese Journal of Contemporary Pediatrics 2019;21(4):381-386
		                        		
		                        			OBJECTIVE:
		                        			To study the etiology and genetic diagnosis of children with short stature.
		                        		
		                        			METHODS:
		                        			A retrospective analysis was performed to study the etiological distribution and clinical features of 86 children with short stature.
		                        		
		                        			RESULTS:
		                        			A total of 6 causes were observed in these children, among which idiopathic short stature (ISS, 41%) and growth hormone deficiency (GHD, 29%) were the most common causes, followed by genetic diseases (14%). There were no significant differences in age at the time of diagnosis, body height, body length and weight at birth, body height of parents and insulin-like growth factor-1 levels between the genetic disease group and the ISS/GHD groups (P>0.05). Compared with the ISS group, the genetic disease group had significantly lower deviation from the 3rd percentile for the height of children of the same age and sex (ΔP3) and height standard deviation score (P<0.05), while there were no significant differences between the genetic disease and GHD groups (P>0.05). The analysis of the clinical manifestations for the genetic disease group showed heterogeneity and phenotypic overlap in children with different genetic diseases.
		                        		
		                        			CONCLUSIONS
		                        			ISS, GHD and genetic diseases are major causes of short stature in children. For children with severe short stature, genetic testing should be performed to make a definitive diagnosis after GHD has been excluded.
		                        		
		                        		
		                        		
		                        			Body Height
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Dwarfism, Pituitary
		                        			;
		                        		
		                        			Genetic Testing
		                        			;
		                        		
		                        			Growth Disorders
		                        			;
		                        		
		                        			Human Growth Hormone
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
            
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