Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature / 中国当代儿科杂志

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.

PTPN11 gene mutation mediated Noonan syndrome in children with idiopathic short stature / 中华内分泌代谢杂志

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.

Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone / 医学前沿

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.

Effect of recombinant human growth hormone on the growth rate, glucose and lipid metabolism and bone metabolism in children with idiopathic short stature / 中国医师进修杂志

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.

Design of the long-term observational cohort study with recombinant human growth hormone in Korean children: LG Growth Study

PURPOSE: Regarding recombinant human growth hormone (rhGH) use in the pediatric population, no long-term follow-up data are available for Korean patients. To fill in the gap of knowledge, a registry study (LG Growth Study) was initiated to assess the safety and effectiveness of four types of rhGH products in real-life settings. METHODS: A total of 4,000 children will be registered and prospectively followed up at 6-month intervals until 2 years after epiphyseal closure to collect data on treatment and adverse events, with primary interest in malignancies and growth outcomes. RESULTS: As of 22 March 2017, approximately 50% (2,024) of the target number of patients have been included in the analysis set: growth hormone deficiency, 1,297 (64.1%); idiopathic short stature, 315 (15.6%); small for gestational age, 206 (10.2%); Turner syndrome, 197 (9.7%); and chronic renal failure, 9 (0.4%). At baseline, median age (years) was 8 (interquartile range [IQR], 5–11); 52% (1,048) were boys; and the majority were at Tanner stage I (83% based on breast/external genitalia, 97% on pubic hair). Median height standard deviation score was -2.26 (IQR, -2.69 to -2.0), and median bone age delay (years) was -1.46 (IQR, -2.26 to -0.78). CONCLUSIONS: This registry study will provide the opportunity to assess the risk of malignancies as well as the general safety data in Korean pediatric patients receiving rhGH. In addition, the long-term effectiveness of rhGH and comparative data between different disease entities will provide practical insight on the standard rhGH treatment.

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature / 소아과

PURPOSE: Short stature affects approximately 2%–3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. METHODS: We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. RESULTS: A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX. CONCLUSION: In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Novel genetic cause of idiopathic short stature

Traditionally, the growth hormone – insulin-like growth factor I (GH – IGF-I) axis is the most important signaling pathway in linear growth, and defects in this axis present as growth hormone deficiencies or IGF-I deficiencies. However, subtle changes in serum levels of GH or IGF-I, caused by gene mutations involved in the GH – IGF-I axis, can present as idiopathic short stature (ISS). This paper briefly discusses GHR and IGFALS. In addition, recent studies have shown that many factors, including paracrine signals, extracellular matrix, and intracellular mechanisms of chondrocytes, regulate the growth plate independent of the GH – IGF-I system. Rapid development of diagnostic technologies has enabled discovery of many genetic causes of ISS. This paper discusses 5 genes, SHOX, NPR2, NPPC, FGFR3, and ACAN, that may lead to better understanding of ISS.

Effect of growth hormone treatment on children with idiopathic short stature and idiopathic growth hormone deficiency

PURPOSE: There are inconsistencies in the results reported in a small number of previous studies into growth hormone (GH) treatment in Korean children with idiopathic short stature (ISS) and idiopathic growth hormone deficiency (IGHD). Thus, the authors retrospectively compared the effects of GH in ISS and IGHD. METHODS: From the medical records of 26 ISS and 30 IGHD children, auxological and biochemical changes including chronologic age (CA), bone age (BA), height standard deviation score (HT-SDS), predicted adult height (PAH), midparental height (MPH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) were compared. RESULTS: Before treatment, IGHD group had younger BA, lower BA/CA ratio, and lower IGF-1 level than those in the ISS group. During GH treatment, the levels of IGF-1 and IGFBP-3 were not different. Although annual BA increment was higher in IGHD group, and annual PAH-SDS increment was higher in ISS group, annual HT-SDS increments were not different. Both HT-SDS and PAH-SDS in the ISS group increased significantly until the end of the second year, and then those were not significantly different from MPH-SDS. In the IGHD group, the HT-SDS showed a significant increase till the end of the second year, and the PAH-SDS was not significantly changed at each year, but both HT-SDS and PAH-SDS were not significantly different from MPH-SDS at the end of the third year. CONCLUSION: During GH treatment, both HT-SDS and PAH-SDS approached the genetic target range of MPH-SDS after 2 years in ISS children and 3 years in IGHD children.

Effects of growth hormone on serum levels of Ghrelin, LP, IGF-1 and IGFBP3 in children with idiopathic short stature / 中国生化药物杂志

Objective To study the effect of growth hormone on serum levels of Ghrelin, leptin(LP), insulin like growth factor-1(IGF-1) and insulin-like growth factor binding protein 3(IGFBP3) in children with idiopathic short stature(ISS).Methods 86 patients of ISS who received therapy from September 2013 to September 2015 were selected.According to random number table,those patients were divided into observation group ( n=43) and the control group (n=43).Control group was treated with routine nutrition therapy, while the observation group was added with recombinant human growth hormone.The Ghrelin, LP, IGF-1, IGFBP3 levels and height pre-and post-treatment were compared.Results After treatment, the level of Ghrelin in observation group [ ( 4.85 ±0.41 ) ng/mL ] was lower than that of control group [ ( 5.63 ±0.62 ) ng/mL ] , the level of LP [ ( 6.53 ± 0.78)mg/L] was higher than that of control group[(5.49 ±0.62)mg/L](all P<0.05); the levels of IGF-1[(387.94 ±47.38)ng/mL] and IGFBP3 [(6.74 ±0.73)μg/mL]in the observation group were higher than that of the control group[(243.54 ±36.82)ng/mL,(4.85 ±0.61)μg/mL](all P<0.05); the height in the observation group[(110.17 ±8.12)cm] was higher than that of control group[(114.58 ±9.40)cm](P<0.05).Conclusion Recombinant human growth hormone is well for ISS, which can effectively improve Ghrelin, LP, promote physical growth IGF-1, IGFBP3 levels, promote growth.

Clonidine-stimulated growth hormone concentrations (cut-off values) measured by immunochemiluminescent assay (ICMA) in children and adolescents with short stature

OBJECTIVES: To establish cut-off values for growth hormone concentrations using clonidine as a secretagogue and an immunochemiluminescent assay as the method of measurement and to analyze the response time as well as the influence of gender, nutritional status and pubertal stage. METHODS: A total of 225 tests were performed in 3 patient groups, categorized as group 1 (normal), group 2 (idiopathic short stature) and group 3 (growth hormone deficiency). Among the 199 disease-free individuals, 138 were prepubertal, and 61 were pubertal. Clonidine (0.1 mg/m2) was orally administered, and the growth hormone level was measured by immunochemiluminescent assay. The growth hormone peak and the difference between the growth hormone peak and the baseline level were then analyzed. Statistical analyses were performed using Student’s t-test or the Mann-Whitney test and Kruskal-Wallis test followed by Dunn’s post hoc test. Cut-off values were determined using a receiver operating characteristic curve. RESULTS: Group 1 and group 2 had no difference in growth hormone peak, gender, body mass index standard deviation score, or pubertal stage. Group 3 exhibited a significantly lower growth hormone peak than the other groups did. The receiver operating characteristic curve demonstrated that growth hormone concentrations ≥ 3.0 ng/mL defined responsiveness to clonidine. In total, 3.02% of individuals in group 1 and group 2 were considered false positive, i.e., these children lacked growth hormone deficiency and had a peak below 3.0 ng/mL. CONCLUSION: Clonidine-stimulated growth hormone concentrations ≥3 ng/mL, as measured by immunochemiluminescent assay, suggest responsiveness to the stimulus regardless of gender, body mass index standard deviation score or pubertal stage.

Estatura final en niños con talla baja idiopática tratados con hormona del crecimiento / Adult height of children with idiopathic short stature treated with growth hormone therapy

Introducción: La talla baja idiopática (TBI) se define como talla ≤ 2 desviaciones estándar (DE) sin causa precisada. El uso de la hormona de crecimiento (GH) en TBI es controvertido y no existen resultados de talla final (TF) en pacientes chilenos. El objetivo de este trabajo es comparar la TF de pacientes con TBI tratados con GH con la predicción de talla adulta al inicio de tratamiento. Pacientes y método: 18/47 pacientes con TBI tratados con GH y que alcanzaron su TF. Se definió TF con edad ósea (EO) ≥ 17 años en hombres y ≥ 15 años en mujeres. Para comparar se consideró la DE de la talla según curvas NCHS al inicio y final de tratamiento. El pronóstico de talla adulta (PTA) se calculó utilizando la EO mediante el método de Bayley-Pinneau. Resultados: La talla inicial fue 133,1 ± 6,8 cm (-2,1 ± 0,85 DE) y el PTA de -1,94 ± 0,86 DE. Los pacientes se trataron desde los 11,6 ± 1,2 años durante un tiempo de 1,56 ± 0,65 años. Al año de tratamiento su talla fue -1,64 ± 0,69 DE y la talla final fue -1,28 ± 0,62 DE (163,76 ± 7,22 cm). Se obtuvo un aumento en la TF de 2,67 ± 5,88 cm (equivalente a 0,67 ± 0,9 DE). Conclusión: Nuestros resultados demuestran que el tratamiento con GH fue eficaz para incrementar TF en pacientes con TBI, con una duración mayor a un año de tratamiento. Hasta donde sabemos este constituye el primer reporte de talla final en pacientes chilenos con TBI tratados con GH.

Introduction: Idiopathic short stature (ISS) is defined as a height of < - 2 standard deviations (SD) from the mean for age. The use of Growth Hormone (GH) in ISS is controversial, and there are not results for adult height (AH) in Chilean patients with ISS treated with GH. The objective of the study is to compare AH in patients treated with GH with the height prediction at beginning of treatment. Patients and Method: AH was considered with bone age ≥ 17 in males and ≥15 in females. The height SD according to the NCHS curves at beginning and ending of treatment were used for the comparison. Height prediction (HP) was calculated by Bayley-Pinneau method. Results: AH was reached by 18/47 patients with ISS treated with GH. Initial height -2.1 ± 0.85 SD (133.1 ± 6.8 cm) and HP -1.94 ± 0.86 SD, and were treated since 11.6 ±1.2 years old. After one year of treatment their height was -1.64 ±0.69 SD, and AH was -1.28 + -0.62 SD (163.76 +-7.22 cm). Conclusion: It is suggested that treatment with GH for ISS is effective to increase AH. Although with wide individual variability, a mean increase of 0.67 ± 0.9 SD (+2.67 cm) was obtained in the AH. This is the first report on Adult Height in Chilean patients.

Clinical significance of monitoring bone turnover markers changes before and after growth hormone treatment of prepubertal children with idiopathic short stature / 中华实用儿科临床杂志

Objective To detect the levels and study the clinical significance of serum procollagen type Ⅰ amino-terminal propeptide (PINP) and β-C-telopeptides of type Ⅰ collagen (β-CTX) as bone turnover markers in recombinant human growth hormone (rhGH) treatment of prepuberty idiopathic short stature (ISS) children.Methods Forty patients of ISS (18 boys and 22 girls) had been collected and treated with GH 0.15 IU/(kg · d) injection every night.Serum levels of PINP,β-CTX,insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) were measured by electrochemiluminescence immunoassay in ISS before treatment and after 3,6 months,and they were also measured in 50 healthy children of the healthy control group,and the height,weight,body mass index,height standard difference score (HtSDS),bone age and growth rate were recorded.Results (1) In ISS group,the serum level of PINP[(479.51 ± 134.61) μg/L] was lower than that of the healthy control group [(651.31 ± 212.41) μg/L],the level of β-CTX[(0.84 ± 0.33) μg/L] was higher than that of the healthy control group [(0.50 ± 0.15) μg/L].The differences were statistically significant (t =2.276,-2.709,all P ＜ 0.05).(2) The serum levels of PINP and β-CTX had no significant difference in 18 boys and 22 girls before and after GH treatment (P＞0.05) of ISS.After 3 months of GH treatment,the serum levels of PINP[(736.15 ± 156.59) μg/L] and β-CTX [(1.08 ± 0.27) μg/L] were higher than those before treatment in 40 cases,and the difference was statistically significant (t =4.736,2.497,all P ＜ 0.05),as the increase of PINP was particularly significant.HtSDS (-2.95 ±0.43),compared with before treatment (-2.69 ± 0.58),was significantly different (t =2.714,P ＜ 0.05).However,after 6 months of GH treatment,the levels of PINP[(860.90 ±254.59) μg/L] and β-CTX[(0.94 ±0.32) μg/L] increased slowly (t =1.366,-0.831,all P ＞ 0.05).HtSDS (-2.51 ± 0.54) showed no significant difference (t =1.609,P ＞ 0.05) compared with 3 months of treatment.(3) The serum level of PINP was positively correlated with IGF-1 and IGFBP3 (r =0.636,0.673,all P ＜ 0.05),and there was no correlation with β-CTX (r =0.336,P ＞0.05).PINP and β-CTX had significant correlation with HtSDS (r =0.655,0.782,all P ＜ 0.05).Conclusions The serum PINP and β-CTX as bone turnover markers in serum can be used as one of the early supplementary indicators to predict GH response of ISS.

The expression and significance of serum ghrelin, leptin, IGF-1, and IGFBP3 in children with idiopathic short stature / 中华内分泌外科杂志

Objective To examine the expressions of serum growth hormone (ghrelin), leptin (LP), in sulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP3) in children with id-iopathic short stature (ISS), and their significance. Methods A total of 40 patients with ISS were selected from May. 2012 to Oct. 2014 in Fuyang Maternal and Child Health Hospital, while a total of 40 children in good health were selected as the control group. Serum ghrelin and LP levels were measured by ELISA. Serum IGF-1 and IGF-BP3 levels were detected by chemiluminescence immune assay. Results were analyzed statistically. Results The height, weight, BMI, GH, serum LP, IGF-1, and IGFBP3 levels in the observation group were significantly lower than those in the control group, while serum ghrelin expression level was significantly higher than that in the control group(P<0.05). The correlation analysis showed that ghrelin and LP were negatively correlated(r=-0.611, P<0.01), ghrelin and IGF-1 levels were negatively correlated(r=-0.520, P<0.05), Ghrelin and IGFBP3 were pos-itively correlated (r=0.586, P<0.01), IGF-1 and IGFBP3 was negatively correlated (r=-0.576, P<0.01), and LP and IGFBP3 were negatively correlated (r=-0.609, P<0.01). Conclusions It shows that ghrelin, LP, IGF-1, and IGFBP3 levels in children with ISS are related to growth hormone secretion status. The interactions between ghre-lin and insulin-like growth factor axis regulate growth and development of children.

Association of serum components of GH axis with GHR exon 3 polymorphism in idiopathic short stature children / 天津医药

Objective To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in idiopathic short stature (ISS) children. Methods Genomic DNA was extracted and isolat-ed from peripheral leukocytes in 108 ISS children. GHR-exon 3 polymorphism was analyzed with multiplex poly-merase chain reactions (PCR) assay. According to the results of genotype, ISS children were divided into GHRfl group and GHRd 3 group. The height and weight were recorded in two groups. The body mass index (BMI) and BMI standard deviation score (SDS) were measured. The serum levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGF-1 SDS and IGFBP3 SDS were calculated. GH stimulation test was used to measure the serum GH peak value. Fifty-five ISS chil-dren were treated with recombine human GH [0.15 IU/(kg·d)] for three months to analyse the association of IGF-1 response of GH treatment and genotypes. Results There were 63 GHRfl and 45 GHRd3 in 108 ISS children. There were no signifi-cant differences in BMI, IGF-1, IGFBP3, GH peak, IGF-1 SDS and IGFBP3 SDS between two groups (P>0.05). Multiple stepwise regression analysis showed that age, IGFBP3, lg (BMI) and lg (GH peak) were influencing factors of lgIGF-1 (P<0.05). In 55 ISS children treated with rhGH, there were 34 cases of GHRd3. The differences of △IGF-1 and △IGF-1 SDS were higher in GHRd3 group than those of GHRfl group (n=21). Conclusion The GH sensitivity may be a risk factor in ISS children, which may not be related with GHR polymorphism.

Controversias en el manejo de la talla baja idiopática

La talla baja idiopática (TBI) es un diagnóstico de exclusión que abarca un amplio y heterogéneo grupo de niños aparentemente sanos pero con talla inferior a -2 desviaciones estándar. En los Estados Unidos está aprobado el uso de hormona de crecimiento (HC) en niños con TBI, a diferencia de la mayoría de países Europeos. La respuesta terapéutica de los niños con TBI tratados con HC es muy variable y dependiente de múltiples factores al inicio y durante el tratamiento, por lo cual el beneficio de su uso no ha podido establecerse de forma consensual. Esta revisión recoge información actualizada sobre los más recientes estudios publicados en pacientes con TBI tratados con HC hasta alcanzar talla final, los diferentes factores asociados a la respuesta terapéutica, los efectos metabólicos, psicosociales y efectos adversos de la HC, y sobre otras opciones terapéuticas a considerar tales como HC con análogos de la GnRH, inhibidores de aromatasa e IGF1 humana recombinante.

Idiopathic short stature (ISS) is an exclusion diagnostic which includes a broad and heterogeneous group of supposedly healthy children with height below -2 standard deviations. In the United States, treatment with growth hormone (GH) is approved for children with ISS, as opposed to the majority of European countries. The final height of children with ISS whom are treated with GH is highly variable and dependent on multiples factors at the beginning and during the treatment. For this reason, the indication of GH therapy in ISS children is not consensual. This revision contains actual data about the most recently published studies in patients with ISS treated with GH until final height, associated factors to height gaining, metabolic, psychosocial and adverse events, and finally, other therapeutic options such as GH combined with GnRH analogues, aromatase inhibitors and recombinant human IGF1.

A Leri-Weill dyschondrosteosis patient confirmed by mutation analysis of SHOX gene

Leri-Weill dyschondrosteosis is characterized by SHOX deficiency, Madelung deformity, and mesomelic short stature. In addition, SHOX deficiency is associated with idiopathic short stature, Turner syndrome, and Langer mesomelic dysplasia. We report the first case of a Leri-Weill dyschondrosteosis patient confirmed by SHOX gene mutation analysis in Korea. The patient, who was a 7-year-old female, showed short stature. Her height and weight were 108.9 cm (A (p.W164X) mutation of the SHOX gene. Accordingly, this patient was diagnosed with Leri-Weill dyschondrosteosis. Recently, many mutations have been reported in the SHOX gene. However, to date, mutation analysis of the SHOX gene for Leri-Weill dyschondrosteosis has not been reported in Korea as yet. We report the first case of a Leri-Weill dyschondrosteosis patient confirmed by mutation analysis of the SHOX gene.

Effect of recombinant human growth hormone on serum levels of insulin like growth factor 1 and insulin-like growth factor binding protein 3 in children with idiopathic short stature / 中国生化药物杂志

Objective To investigate the effect of recombinant human growth hormone on serum levels of insulin like growth factor 1(IGF-1) and insulin-like growth factor binding protein 3(IGFBP-3)in children with short stature.Methods 48 children were diagnosed with idiopathic short stature were collected.All children were randomly divided into control group and experimental group ,24 cases in each group.Children in control group received nutritional therapy, children in experimental group were given recombinant human growth hormone on the basis of control group treatment, both group were treated for 12 month.After the treatment, the serum levels of IGF-1,IGFBP-3 and the height were detected in all children.Results Compared with control group post-treatment,,the serum level of IGF-1 was higher in experimental group ( P<0.05 );the serum level of IGFBP-3 was higher in experimental group ( P<0.05 );the height was higher in experimental group ( P<0.05 ) .Conclusion Recombinant human growth hormone can significantly increase the serum levels of IGF-1 and IGFBP-3 in children with idiopathic short stature, promote children growth, and have a guiding significance for clinical.

Comparison between the growth response to growth hormone (GH) therapy in children with partial GH insensitivity or mild GH deficiency / Comparação entre a resposta de crescimento ao tratamento com hormônio de crescimento (GH) em crianças com insensibilidade parcial ao GH ou deficiência de GH leve

Objectives: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD.Subjects and methods: Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1 st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS).Results: Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD.Conclusion: GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.

Objetivos: O tratamento com GH é ainda controverso, salvo na deficiência grave de GH (SGHD). O objetivo deste estudo foi comparar a resposta ao tratamento com GH em indivíduos com insensibilidade parcial ao GH (PGHIS) e na deficiência moderada do GH (MGHD) com SGHD.Sujeitos e métodos: Quinze pacientes com PGHIS, 11 com MGHD e 19 com SGHD, seguidos por mais de um ano no Sistema Único de Saúde, foram avaliados antropométrica e laboratorialmente, no início, com um ano de tratamento e na última avaliação (tempo máximo de dez anos na SGHD, quatro anos na MGHD e oito anos na PGHIS).Resultados: O escore de desvio-padrão (EDP) da estatura inicial foi menor nos indivíduos com SGHD do que naqueles com MGHD e PGHIS. Embora o aumento no EDP da estatura no primeiro ano em comparação com o inicial não fosse diferente entre os grupos, o EDP da altura no primeiro ano de tratamento permaneceu menor na SGHD que na MGHD. Não houve diferença no EDP da estatura na última avaliação entre os três grupos. O tratamento com GH, no período completo da observação, provocou uma tendência a menor aumento no EDP da estatura nos pacientes com PGHIS que naqueles com SGHD, entretanto aumentos semelhantes foram encontrados nos grupos MGHD e SGHD.Conclusão: O tratamento com GH aumentou a estatura nos indivíduos com PGHIS e produziu efeitos similares na estatura em MGHD e SGHD.

Comparison of Growth Hormone Treatment in Patients with Idiopathic Short Stature and Idiopathic Growth Hormone Deficiency / 전남의대학술지

After recombinant human growth hormone (rhGH) was introduced in the treatment of patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS), many studies have addressed the effect of GH treatment and changes in the height standard deviation score (SDS) after GH treatment. However, few studies comparing the effect of GH in Korean patients with idiopathic GHD and ISS have been designed. Therefore, this study focused on the difference in effect of GH treatment between the two groups. We retrospectively reviewed the height SDS of 34 patients with idiopathic GHD and 12 patients with ISS. The mean ages of the patients with idiopathic GHD and ISS were 9.84+/-2.09 and 10.72+/-1.48 years, respectively. All patients were treated with GH for 1 year and body parameters were recorded before and after the GH treatment. Change in height SDS in patients with idiopathic GHD was significantly higher than that in patients with ISS (0.62+/-0.33 vs. 0.40+/-0.27, p=0.03). However, body mass index, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were not significantly different between the two groups after GH treatment. These results suggest that GH treatment has a more powerful effect on increasing height SDS in patients with idiopathic GHD than in patients with ISS.

Comparison of Growth Hormone Treatment in Patients with Idiopathic Short Stature and Idiopathic Growth Hormone Deficiency / 전남의대학술지

After recombinant human growth hormone (rhGH) was introduced in the treatment of patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS), many studies have addressed the effect of GH treatment and changes in the height standard deviation score (SDS) after GH treatment. However, few studies comparing the effect of GH in Korean patients with idiopathic GHD and ISS have been designed. Therefore, this study focused on the difference in effect of GH treatment between the two groups. We retrospectively reviewed the height SDS of 34 patients with idiopathic GHD and 12 patients with ISS. The mean ages of the patients with idiopathic GHD and ISS were 9.84+/-2.09 and 10.72+/-1.48 years, respectively. All patients were treated with GH for 1 year and body parameters were recorded before and after the GH treatment. Change in height SDS in patients with idiopathic GHD was significantly higher than that in patients with ISS (0.62+/-0.33 vs. 0.40+/-0.27, p=0.03). However, body mass index, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were not significantly different between the two groups after GH treatment. These results suggest that GH treatment has a more powerful effect on increasing height SDS in patients with idiopathic GHD than in patients with ISS.