Idiopathic Short Stature Group Research Articles

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in North Indian Population.

In the hypothalamic-pituitary-gonadotrophin (HPG) axis, estrogen plays a key role in the bone maturation regulation and growth plates closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in the North Indian population. Four SNPs of the ESR1 gene (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in 52 ISS patients and 68 controls. Linkage disequilibrium (LD) and haplotyping were done by SNPstat and SHESISplus softwares. Extent of LD was determined by calculating D' and r2 values in SNPs paired combinations. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility as compared to controls. The frequencies of the rs6557177 CC genotype (p=0.030; OR=0.13; 95% CI:0.01-1.10) and rs543650 genotype TT (p =0.043; OR=0.29; 95% CI: 0.09-0.92) were observed to be increased in ISS group as compared with the control group. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 shown strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Our study showed that CC genotype at rs6557177 and TT genotype of rs543650 of ESR1 constitutes risk factor for developing ISS in North Indian children. In the future, these findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study.

To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings. This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation. Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection. Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS.

Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature

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. 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. 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). 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.

Levels and diagnostic values of serum visceral adipose tissue-derived serine protease inhibitor and secreted frizzle-related protein 5 in children with idiopathic short stature

Abstract Background: Idiopathic short stature (ISS) is a common type of short stature. We aimed to analyze the diagnostic values of serum visceral adipose tissue-derived serine protease inhibitor (Vaspin) and secreted frizzle-related protein 5 (SFRP5) for ISS children. Methods: Sixty-five ISS children treated from February 2019 to June 2022 were selected as an ISS group, while another 65 healthy children receiving physical examination in the same period were selected as a healthy group. Their general data, physical development status, levels of serum Vaspin and SFRP5, and levels of serum growth hormone-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis-related indicators were compared. Results: The ISS group had lower body height, body weight, bone age, growth velocity and serum SFRP5 level and higher serum Vaspin level than those of the healthy group (P&lt;0.05). The levels of serum GHRH, GH and IGF-1 were lower in the ISS group than those in the healthy group (P&lt;0.05). Body height, body weight, bone age, growth velocity, and levels of GHRH, GH and IGF-1 were negatively correlated with serum Vaspin level (r&lt;0, P&lt;0.05) but positively correlated with serum SFRP5 level (r&gt;0, P&lt;0.05). The areas under the ROC curves of serum Vaspin and SFRP5 and their combination for the diagnosis of ISS were 0.871 [95% confidence interval (CI): 0.812-0.929], 0.880 (95% CI: 0.824-0.935) and 0.942 (95% CI: 0.907-0.977), respectively. Conclusions: Children with ISS have a higher level of serum Vaspin but a lower level of SFRP5, and the combined detection has a higher diagnostic value for ISS.

Growth hormone therapy response in children with short stature

BackgroundShort stature is one of the main causes of children referral to pediatric endocrinologists. Common etiologies include idiopathic growth hormone deficiency (IGHD), small for gestational age (SGA), and idiopathic short stature (ISS).ObjectivesThe aim of this study was to assess and compare the response of children with IGHD, ISS, and SGA to growth hormone (GH) therapy.MethodsThis was a mixed cohort study that included 40 children with short stature (classified into IGHD, ISS, and SGA) following up at Diabetes, Endocrine, and Metabolism Pediatric Unit (DEMPU), Cairo University Children’s Hospital. Ages ranged between 3 and 18 years. Recruited cases were evaluated for their 1-year response to GH therapy. In addition to history taking, physical examination, and anthropometric measurements, serum levels of IGF-1 were assayed at recruitment.ResultsAmong the 3 groups, height gain (cm/year) was significantly higher in the IGHD group (6.59 cm/year), followed by the ISS (4.63 cm/year) and SGA groups (4.46 cm/year) (p = 0.039). Using the Bang criterion for first-year responsiveness to GH therapy, most cases (30/40, 75%) were considered poor responders.ConclusionThere is a male predominance in children seeking medical advice for short stature. Starting GH therapy at an older age was associated with poor response. Children with IGHD respond better to GH therapy than those with ISS and SGA.

Relationship Between the Serum FGF21 Level and Growth in Children of Short Stature.

This study investigated the relationship between fibroblast growth factor 21 (FGF21) levels and growth in children with growth hormone deficiency (GHD) and idiopathic short stature (ISS), and the effects of the FGF21 level on response to growth hormone (GH) treatment. We included 171 pre-pubertal children with a GHD (n = 54), ISS (n = 46), and normal height (n = 71). Fasting FGF21 levels were measured at baseline and every 6 months during GH treatment. Factors associated with growth velocity (GV) after GH therapy were investigated. The FGF21 level was higher in short children than in the controls without significant difference between the GHD and ISS groups. In the GHD group, the FGF21 level was inversely associated with the free fatty acid (FFA) level at baseline (r = -0.28, P = 0.039), however, was positively correlated with the FFA level at 12 months (r = 0.62, P = 0.016). The GV over 12 months of GH therapy was positively associated with the delta insulin-like growth factor 1 level (β = 0.003, P = 0.020). The baseline log-transformed FGF21 level was inversely associated with GV with marginal significance (β = -0.64, P = 0.070). The FGF21 level was higher in children of short stature, both those with GHD and the ISS, than in children with normal growth. The pretreatment FGF21 level negatively affected the GV of children with GH-treated GHD. These results suggest the existence of a GH/FFA/FGF21 axis in children.

A Real-World Study of Recombinant Human Growth Hormone in the Treatment of Idiopathic Short Stature and Growth Hormone Deficiency.

ObjectiveThis study aimed to evaluate the clinical efficacy of recombinant human growth hormone (rhGH) in the treatment of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) and to explore the related factors affecting treatment efficacy.MethodsThe current research reflects a real-world study. A total of 79 patients with ISS and 95 patients with GHD (both groups pre-puberty) who had been treated with rhGH for more than one year from January 2010 to September 2019 were included in this study. The patients were divided into two groups, ie, an ISS and a GHD group, respectively. The growth indexes, such as chronological age (CA), bone age (BA), height standard deviation score (HtSDS), insulin-like growth factor-1 (IGF-1) SDS, and body mass index were recorded and compared between the two groups before and after treatment. The treatment efficacy was evaluated according to changes in HtSDS before and after treatment, and the influencing factors of clinical efficacy were analyzed using a multivariate regression model.ResultsAt the start of treatment, the differences in CA, BA, height, weight, sexual development stage, HtSDS, mid-parental height SDS, and IGF-1 SDS between the two groups were not statistically significant (P > 0.05). However, the initial dose of rhGH in the GHD group was significantly lower than in the ISS group (P < 0.001). Following rhGH treatment, the differences in CA, BA, BA/CA ratio, and IGF-1 SDS measured at 6, 12, 18, and 24 months between the ISS and GHD groups were not statistically significant, while the difference in HtSDS measured at 6 months was statistically significant. With the extension of rhGH treatment time, the annual growth rate (GV) gradually decreased, and the difference between HtSDS and the baseline gradually increased; however, the differences between the ISS and GHD groups were not statistically significant. The most important factor affecting the treatment efficacy for patients with ISS was age at the start of treatment; the most important factors affecting the treatment efficacy for patients with GHD were age and IGF-1 SDS.ConclusionRecombinant human growth hormone treatment can significantly improve the height of patients with ISS and GHD. There was no significant difference in growth rate between patients with ISS and those with GHD at relatively high doses. The common factor affecting the treatment efficacy of the two groups was the age at the start of treatment. During treatment, monitored data indicated that rhGH treatment of GHD and ISS thyroid function showed a clinical phenomenon in the form of increased free triiodothyronine, rather than hypothyroidism, which was rarely reported in existing studies.

Linear growth response to growth hormone therapy in underweight versus normal weight short children

Introduction Physiologically, growth hormone (GH) increases lean body mass and has a lipolytic function. However, long-term changes in weight status during GH treatment, as a function of pretreatment weight status have not previously been reported in large data sets.Aim To identify the growth response to GH therapy in those who were before treatment underweight versus normal weight short children.Patients and methods A retrospective study, we studied the auxologic data of 78 short, prepubertal children [height standard deviation score (HtSDS) less than −2 SDS below the mean for age and sex] with normal GH secretion [idiopathic short stature (ISS)]. Two groups were identified according to their pretreatment body mass index standard deviation score (BMISDS). Nineteen children were underweight (BMISDS < −2) and 59 children had normal BMISDS (>−2). All children received daily subcutaneous dose of GH (0.03–0.05 mg/kg/day) to keep their insulin-like growth factor-1 (IGF-1) level between 0 and 2 SD for 2 years.Results Before GH treatment, the underweight ISS group had significantly lower IGF-1 level versus the normal weight group with IGF-1 SD −1.633±0.766 SD versus −0.749±1.197 SD, respectively. Age and HtSDS did not differ among the two underweight and normal weight groups. Treatment with GH for 2 years was associated with a significant increase in the BMISDS in the underweight group (BMISDS increased by 0.45 SD) from −2.063±0.344 before treatment with GH versus −1.633±0.766 after treatment but not in the normal weight group. The HtSDS increased significantly in both groups after GH therapy, but the increase was greater in children with normal weight versus those with underweight as the increment in HtSDS was 0.42 and 0.374 SD, respectively. The difference of HtSDS from mid-parental HtSDS in low BMI versus normal BMI groups was −0.91 and −1.212 SD, respectivelyConclusions GH therapy for 2 years significantly increased the IGF-1 level and improved BMISDS and HtSDS in underweight children with ISS. The BMISDS was better in the underweight group, but their HtSDS was less compared with the normal weight group.

Correlation of body mass index to Ghrelin and IGF-1 among children with short stature

ObjectiveTo assess the BMI among children with Growth Hormone Deficiency (GHD) and Idiopathic Short Stature (ISS) and its correlation to ghrelin, Growth Hormone (GH), and Insulin-like Growth Factor-1 (IGF-1) levels. MethodsA cross-sectional descriptive study in which 42 patients attending the Pediatric endocrine clinic were enrolled, allocated into two groups: group I: GHD children; group II: ISS children. Ghrelin, IGF-1 and GH in both groups were measured. ResultsGhrelin was significantly higher among GHD group (p < 0.001). Overall, there was a strong negative correlation between IGF-1 and ghrelin (r = -0.977, p-value = < 0.001) while a moderate positive correlation between ghrelin and BMI (r = 0.419, p-value = 0.006). There was a weak positive non-significant correlation between IGF-1 and BMI (r = 0.276, p-value = 0.077). In GHD group, there was a weak positive non-significant correlation between ghrelin and GHmax measurement (r = 0.052, p-value = 0.824), while a weak negative non-significant correlation between both variables in ISS group (r = -0.243, p-value = 0.288). In GHD group, there was a moderate positive correlation between ghrelin and BMI (r = 0.500, p-value = 0.021), but weak negative non-significant correlation between both variables in ISS group (r = -0.255, p-value = 0.265). ConclusionThere was a negative feedback loop between ghrelin and IGF-1, whereas a positive feedback between ghrelin and BMI. BMI was more affected in the ISS group but was non-significantly correlated with ghrelin. There was no significant compensatory response of ghrelin suggesting its contribution to the pathogenesis of ISS.

Effect of body mass index on peak growth hormone level after growth hormone stimulation test in children with short stature.

PurposeThe aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature.MethodsData were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing.ResultsOf the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus.ConclusionsThe BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.

Comparison of the efficacy and safety of recombinant human growth hormone in treating idiopathic short stature and growth hormone deficiency in children

PurposeThe present study aimed to compare the efficacy and safety of recombinant human growth hormone (rhGH) therapy between children with idiopathic short stature (ISS) and growth hormone deficiency (GHD). MethodsA total of 150 pediatric patients with ISS and 153 pediatric patients with GHD who received rhGH treatment for more than one year from 2005 to 2016 were enrolled. Growth velocity (GV); height standard deviation (HtSD); insulin-like growth factor-1 standard deviation (IGF-1SD); body mass index (BMI); and the incidence of fasting hyperglycemia, fasting hyperinsulinemia, and hypothyroidism were recorded and compared. ResultsAt the beginning of treatment, chronological age, bone age, height, and BMI were not statistically significant between the two groups. rhGH dosage in ISS was significantly higher compared with GHD (P = 0). GV from half a year to three years after rhGH therapy was higher in the GHD group compared with the ISS group, but the differences were not statistically significant (P > 0 .05). HtSD increased in the two groups after rhGH therapy. HtSD at the beginning and after three years of therapy was not different between groups except for after half a year of therapy. HtSD in patients with ISS was significantly higher compared with GHD (P < 0 .05). The incidence of hypothyroidism was significantly higher in the GHD group compared with the ISS group (13.72% vs. 6.0%; P < 0.05). Moreover, the incidence of hyperinsulinemia was significantly higher in the ISS group compared with the GHD group (15.33% vs. 7.84%; P < 0 .05). ConclusionsrhGH increases growth in children with ISS and GHD. Fasting insulin and thyroid function were closely monitored for long-term follow up.

MON-113 The Effect of Body Mass Index on the Peak Growth Hormone Level After Growth Hormone Stimulation Test in Children with Short Stature

Objective: The aim of this study is to evaluate the effect of body mass index (BMI) on peak growth hormone (GH) response after GH stimulation test in children with short stature.Methods: Data was obtained from retrospective review of medical records who visited the pediatric endocrinology at St. Vincent hospital of catholic university for short stature from January 2010 to June 2019. We studied 115 children (aged 3-17 years old) whose height was less than 3percentile for one’s age and sex and who underwent GH stimulation test {GH deficiency (GHD) = 47, Idiopathic short stature (ISS) = 68)}. Peak GH response was stimulated by dopamine (n=111), clonidine (n=7), glucagon (n=19), insulin (n=56) and arginine (n=32). Birth weight, parental height, chronologic age, bone age, height SDS (standard deviation score), weight SDS, BMI SDS hemoglobin, fT4, T3 TSH, cortisol, ACTH, GH, IGF-1 SDS, IGF-BP3 SDS and peak stimulated GH were analyzed.Results: In the characteristics of subject, weight SDS and BMI SDS in GHD group were increased than ISS group (p<0.000, p=0.000). Free T4 was decreased in GHD group than ISS group (p=0.012). In total group, BMI SDS was associated negatively with peak GH level stimulated by dopamine (r=-0.419, p<0.000), insulin (r=-0.271, p=0.044) and arginine (r=-0.368, p=0.038), but did not showed correlation with peak GH level stimulated by glucagon. In GHD group, BMI SDS showed negative correlation with peak GH level using dopamine (r=-0.356, p=0.015) and arginine (r=-0.509, p=0.022). In ISS group, BMI SDS was correlated negatively with peak GH using dopamine (r=-0.330, p=0.007). In multivariate regression analysis of GHD group, weight SDS and BMI SDS were the only two significant predictors of peak GH response in stimulation test stimulated by dopamine (ß=-0.576, p=0.015) and arginine (ß=-0.097, p=0.022). In ISS group, only mother’s height (ß=0.474, p=0.000) and TSH (ß=-2.251, p<0.000) were demonstrated statistically significant predictors of peak GH stimulated by dopamine in multivariate regression analysis. In case of using insulin as a stimulant in ISS group, there is nothing which has statistical significance as a predictor of peak GH response in multivariate regression analysis.Conclusion: BMI was associated negatively with peak GH response after GH stimulation test in children with short stature, especially in GHD group.

SAT-106 Growth Hormone Treatment Response in Children

OBJECTIVES: Growth hormone (GH) therapy is an effective treatment in addressing growth failure in children with GH deficiency (GHD). It has also been increasingly used in non-GH deficient (nGHD) conditions. We sought to report the growth response of GHD and nGHD patients who received GH therapy at a tertiary care center. METHODS: Data was collected from health records of patients followed in the endocrinology clinic at Alberta Children’s Hospital, Calgary, Canada, from 2005 to 2019, and used to analyze clinical responses based on indication for GH treatment. RESULTS: A total of 167 patient records (87 males and 80 females) were used for analysis. The average age at the start of GH therapy was 7.3 years (range 0.25 to 16.98 yrs). 74 patients were in the GHD group while 93 were nGHD. Of the patients in the nGHD group, the most common diagnosis were: idiopathic short stature (ISS)(n=45), Turner syndrome (TS)(n=26), and Prader Willi Syndrome (PWS)(n=8). The mean height velocity (HV) in year 1 was highest in the GHD group at 11.68 cm/year (n= 62, sd = 5.93), followed by ISS at 9.41cm/year (n = 52, sd = 4.34). The mean first year HV of those who had received chemotherapy (n= 5, mean = 5.48, sd = 1.92) or had Turner syndrome (n= 24, mean = 7.20, sd = 2.15) was significantly lower than both the GHD and ISS groups. GH peak during a GH stimulation test at baseline was not correlated to the first year height velocity while on GH treatment. However there was a negative linear correlation between baseline IGF1 level and first year height velocity (Spearman’s rho = 0.312216, p-value= 0.01516). Age at GH initiation was negatively correlated with height velocity during GH treatment. Height velocity over time decreased sharply from year 1 to year 3, and became stable for the remaining years of GH therapy. For the entire group, HV for years 1-5 was 9.81 (sd=4.83), 7.40 (sd=2.89), 6.29 (sd=2.38), 5.92 (sd=2.56), 5.66 (sd=2.51). There is no significant correlation between GH dose and height velocity response after adjusting for diagnosis. CONCLUSION: In our population, the response to GH therapy was consistent with those reported in the literature. Response to GH therapy was not associated with GH peak on stimulation but rather to baseline IGF-1 level and age at initiation. Although peak GH to stimulation is required to obtain public funding for GH therapy, these findings demonstrate that GH stimulation test results may not indicate which patients may benefit the most from GH therapy. Follow-up until final adult height will allow us to have a better understanding of the efficacy of GH therapy in patients with both GHD and nGHD conditions.

Comparison of Postural Features and Muscle Strength between Children with Idiopathic Short Stature and Healthy Peers in Relation to Physical Exercise

Previous research has reported that children with idiopathic short stature (ISS) showed functional and cognitive impairments. The purpose of this study was to compare muscle strength and body posture between children with ISS treated with growth hormone (GH) and healthy peers (healthy children, HC), and to analyze whether these parameters were affected by physical exercise. Eighteen children for the ISS group (mean age: 10.96 ± 1.68 years) and 26 children for the HC group (mean age: 10.19 ± 1.06 years) were recruited for the study. All participants performed the following assessments: handgrip and Sargent test for the muscle strength evaluation; baropodometric and stabilometric test for the posturographic measures. Data were analyzed with analysis of covariance (ANCOVA) using height and weight as covariate. Groups were then stratified into active and inactive and independent t-tests were used to determine differences between variables. Significance level was set to p &lt; 0.05. Our results showed a significantly lower performance for both hands (p &lt; 0.01) and a greater difference of plantar loading distribution between feet in the ISS compared to the HC groups (p &lt; 0.01). In relation to physical exercise, the HC active group showed the highest handgrip strength values for both hands among the analyzed groups and, moreover, handgrip strength of both ISS active and inactive groups was significantly lower than corresponding CH peers for both hands. Although ISS and HC inactive groups reported an unequal plantar loading distribution between feet (p &lt; 0.05), this asymmetry was not present in both ISS and HC active groups. We assume that GH therapy integrated with physical exercise in young patients with ISS could be suggested to increase muscle strength and body posture improving their quality of life.

Effect of growth hormone treatment on children with idiopathic short stature (ISS), idiopathic growth hormone deficiency (IGHD), small for gestational age (SGA) and Turner syndrome (TS) in a tertiary care center.

Objectives:To assess the long-term effect of growth hormone (GH) therapy in a large cohort of short children with different etiologies.Patients and Methods:We evaluated retrospectively the anthropometric data of 252 short children [height SDS <-2: 154 children with growth hormone deficiency (GHD), 63 with idiopathic short stature (ISS), 26 with SGA, and 9 with Turner syndrome (TS)] who were treated, in our center, with GH between 1-2007 and 1-2018. Before and during recombinamt growth-hormone (recGH) treatment, auxological parameters including height (Ht), weight (Wt), Ht - Z score (HtSDS), body mass index (BMI) and BMISDS were recorded every 6 months; bone age (BA) was assessed every 12 months.Results:At the end of first year of rhGH therapy and after an average of 3 years treatment all groups of short children had significant increase in HtSDS, which was higher in GHD compared to other groups. Children with GHD, SGA, ISS and TS increased their HtSDS by an average of 2.2, 1.46, 0.6 and 0.99 SD, respectively at the end of follow up period (for all groups, p: <0.001). The bone age/chronological age (BA/CA) ratio did not differ significantly among ISS, GHD and SGA groups after GH therapy. The HtSDS gain was higher in children with GHD compared to other ISS, SGA and TS groups (p:< 0.01; p: 0.015 and p: 0.029, respectively). HtSDS improvement occurred during the first 3 years of rhGH therapy. The BMISDS increased significantly in children with GHD, after 3 years of rhGH therapy (p: < 0.001). After rhGH treatment, the BMISDS decreased significantly in children with ISS and SGA (p: < 0.01 and < 0.001, respectively) but did not change in children with TS (p: 0.199).Conclusions:Children with GHD, SGA, ISS and TS exhibited significant increases in HtSDS when treated with rhGH for 3 years. The HtSDS gain was higher in children with GHD compared to other groups. (www.actabiomedica.it)

P.108 Effects of intermittent fasting on body weight, antioxidant defence system, autonomic nervous system balance and activity in female Wistar rats

The aim of the present study was to investigate the differences in the topological organization of functional brain networks between children with growth hormone deficiency (GHD) and those with idiopathic short stature (ISS).Thirty-one children with GHD and fifty-three children with ISS were recruited based on the results of GH stimulation tests. Resting-state fMRI data were acquired from all children. Whole brain functional connectivity density (FCD) analysis and subsequent seed-based functional connectivity analysis were used to explore the differences in functional brain networks between the children with ISS and GHD. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales and FCD values of different brain regions were applied.Compared with the ISS group, the GHD group exhibited significantly decreased FCDs in the left postcentral gyrus, right precentral gyrus and left cerebellar lobules 7b and 6. The subsequent functional connectivity analysis found decreased functional connectivity between lobules 7b and 6 of the left cerebellum as well as the left postcentral gyrus and right precentral gyrus in the GHD group compared to that in the ISS group. In addition, the FCD values of region 6 of the left cerebellum in the GHD group were negatively correlated with the scores on the Symptom Checklist-90 and Eysenck Personality Questionnaire. The FCD value of the left postcentral gyrus in children with ISS positively correlated with IGFBP-3 levels and was approximately correlated with IGF-1 levels.These findings highlight the impact of growth hormone deficiency on the brain network that mainly involves the somatosensory, somatic motor and cerebellum networks, which may contribute to the behavioural problems observed in these children.

P.553 5-HT4R binding is positively correlated with obsessive-compulsive features: a preliminary analysis in healthy volunteers

The aim of the present study was to investigate the differences in the topological organization of functional brain networks between children with growth hormone deficiency (GHD) and those with idiopathic short stature (ISS).Thirty-one children with GHD and fifty-three children with ISS were recruited based on the results of GH stimulation tests. Resting-state fMRI data were acquired from all children. Whole brain functional connectivity density (FCD) analysis and subsequent seed-based functional connectivity analysis were used to explore the differences in functional brain networks between the children with ISS and GHD. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales and FCD values of different brain regions were applied.Compared with the ISS group, the GHD group exhibited significantly decreased FCDs in the left postcentral gyrus, right precentral gyrus and left cerebellar lobules 7b and 6. The subsequent functional connectivity analysis found decreased functional connectivity between lobules 7b and 6 of the left cerebellum as well as the left postcentral gyrus and right precentral gyrus in the GHD group compared to that in the ISS group. In addition, the FCD values of region 6 of the left cerebellum in the GHD group were negatively correlated with the scores on the Symptom Checklist-90 and Eysenck Personality Questionnaire. The FCD value of the left postcentral gyrus in children with ISS positively correlated with IGFBP-3 levels and was approximately correlated with IGF-1 levels.These findings highlight the impact of growth hormone deficiency on the brain network that mainly involves the somatosensory, somatic motor and cerebellum networks, which may contribute to the behavioural problems observed in these children.

Height Gain and Safety Outcomes in Growth Hormone-Treated Children with Idiopathic Short Stature: Experience from a Prospective Observational Study

Background/Objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice. Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data. Results: Compared to children with isolated idiopathic GH deficiency (IGHD), those with ISS were shorter at baseline but had similar age and GH dose. Mean ± SD height SD score (SDS) increase was similar for ISS and IGHD, with 0.6 ± 0.3 (first), 0.4 ± 0.3 (second), 0.3 ± 0.3 (third), and 0.1 ± 0.3 (fourth year) for ISS. Girls with ISS (27% of subjects) were younger and shorter than boys but had similar height gain over time. At NAH in the ISS group (n = 467), mean ± SD age, GH duration, and height SDS were 17.3 ± 2.3 years, 4.6 ± 2.7 years, and –1.2 ± 0.9, respectively. Height gain from baseline was 1.1 ± 1.0 SDS and was greater for boys than girls (1.2 ± 1.0 vs. 0.9 ± 0.9), but boys were treated longer (5.1 ± 2.8 vs. 3.6 ± 2.5 years). Adverse events were reported for 24% with ISS versus 20% with IGHD – most were common childhood conditions or previously reported in GH-treated patients. Conclusions: GH-treated children with ISS achieved substantial height gain, similar to patients with IGHD. Fewer GH-treated girls were enrolled than boys, but with similar height SDS gain over time. No ISS-specific safety issues were identified. Thus, GH treatment of ISS appears to have a safety/effectiveness profile similar to that of IGHD.

Analysis of the value and correlation of IGF-1 with GH and IGFBP-3 in the diagnosis of dwarfism.

Correlation between the value of insulin-like growth factor-1 (IGF-1) in the diagnosis of dwarfism and the levels of growth hormone (GH) and insulin-like growth factor binding protein-3 (IGFBP-3) was investigated. From April 2014 to June 2017, 122 children with dwarfism who were treated in The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University and The First Affiliated Hospital of Xinxiang Medical University were selected as the experimental group, and 51 normal children as the control group. The basic information was recorded in detail; serum GH and IGFBP-3 levels were measured using an arginine stimulation test and an insulin hypoglycemia stimulation test, respectively. According to the peak of GH in the experimental group, there were 65 cases of growth hormone deficiency (GHD) and 57 cases of idiopathic short stature (ISS). The expression levels of IGF-1 of the serum in the experimental and control group were detected by chemiluminescence immunoassay (CLIA). The correlation between IGF-1 and GH, IGF-1 and IGFBP-3 was analyzed. The expression level of serum IGF-1 in GHD group was significantly lower than that in the ISS group (P<0.05). The expression level of serum IGF-1 in GHD group was significantly lower than that in the control group (P<0.05). The expression level of serum IGF-1 in ISS group was significantly lower than that in the control group (P<0.05). The results of partial correlation studies showed that IGF-1 is positively correlated with GH and IGFBP-3. Detection of GH and IGFBP-3 are important for the early diagnosis and comprehensive evaluation of children with dwarfism, and also in the detection of IGF-1 can reflect the therapeutic effect of dwarfism on recombinant human growth hormone (rhGH) treatment, which is worthy of application in clinics.

Differences in the functional connectivity density of the brain between individuals with growth hormone deficiency and idiopathic short stature

PurposeThe aim of the present study was to investigate the differences in the topological organization of functional brain networks between children with growth hormone deficiency (GHD) and those with idiopathic short stature (ISS). MethodsThirty-one children with GHD and fifty-three children with ISS were recruited based on the results of GH stimulation tests. Resting-state fMRI data were acquired from all children. Whole brain functional connectivity density (FCD) analysis and subsequent seed-based functional connectivity analysis were used to explore the differences in functional brain networks between the children with ISS and GHD. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales and FCD values of different brain regions were applied. ResultsCompared with the ISS group, the GHD group exhibited significantly decreased FCDs in the left postcentral gyrus, right precentral gyrus and left cerebellar lobules 7b and 6. The subsequent functional connectivity analysis found decreased functional connectivity between lobules 7b and 6 of the left cerebellum as well as the left postcentral gyrus and right precentral gyrus in the GHD group compared to that in the ISS group. In addition, the FCD values of region 6 of the left cerebellum in the GHD group were negatively correlated with the scores on the Symptom Checklist-90 and Eysenck Personality Questionnaire. The FCD value of the left postcentral gyrus in children with ISS positively correlated with IGFBP-3 levels and was approximately correlated with IGF-1 levels. ConclusionsThese findings highlight the impact of growth hormone deficiency on the brain network that mainly involves the somatosensory, somatic motor and cerebellum networks, which may contribute to the behavioural problems observed in these children.