Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent along with the increasing trend of obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis. This study evaluates the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. Methods: One hundred twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into 3 groups according to body mass index (BMI). Ninety two were obese, and 19 and 10 were overweight and normal weight, respectively. Results: The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (P=0.044). The TyG index and US-FLI did not differ significantly among the 3 BMI groups (P=0.186). Fourteen (11.6 %) of the 121 patients had US-FLI  6, in whom the BMI-SDS and TyG index were higher (P=0.017, P=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI < 6 (P=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI  6 was 8.91, with an area under the curve of 0.785. Conclusion: TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

α-Klotho levels in girls with central precocious puberty: potential as a diagnostic and monitoring marker.

Background: Recent studies suggest a link between the Klotho protein, sex hormones, and insulin-like growth factor-1 (IGF-1), indicating that α-Klotho levels may rise during puberty, including in central precocious puberty (CPP) cases. This study aimed to explore α-Klotho levels in girls with CPP to assess its potential as a diagnostic and monitoring tool for this condition. Methods: In total, 139 girls, comprising 82 patients diagnosed with CPP and 57 healthy prepubertal controls, were enrolled in this study. From March 2020 to May 2023, we assessed both α-Klotho levels and clinical parameters. α-Klotho concentrations were measured using an α-Klotho ELISA kit. For the girls with CPP, we additionally analyzed samples taken 6 months after GnRH agonist treatment. Results: α-Klotho levels were higher in the CPP group compared with the control (CPP group: 2529 ± 999 ng/mL; control group: 1802 ± 675 pg/mL) (P < 0.001), and its level modest decreased after 6 months of GnRH agonist treatment (2147± 789 pg/mL) (P < 0.001). The association between α-Klotho and IGF-1 SDS, follicular stimulating hormone and baseline luteinizing hormone was assessed by partial correlation after adjusting for age, BMI SDS (r= 0.416, p= <0.001; r= 0.261, p= 0.005; r= 0.278, p= 0.002), respectively. Receiver operating characteristic curve analysis identified an α-Klotho cut-off differentiating CPP from controls, with a cut-off of 1914 pg/mL distinguishing girls with CPP from controls with a sensitivity of 69.5% and specificity of 70.2%; the area under the curve was 0.723. Conclusion: The findings of our study are the first step towards deciphering the role of α-Klotho in puberty induction. With additional data and further research, α-Klotho could potentially be utilized as a significant diagnostic and monitoring tool for CPP.

Floating-Harbor Syndrome in a Korean Patient with Short Stature and Early Puberty: A Case Report.

Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionately short stature, lack of expressive language, and distinctive facial features, including a large nose, long eyelashes, deeply set eyes, and a triangular face. We present a case of an 11-year-old Korean girl who was initially suspected of having Noonan-like syndrome but was later diagnosed with Floating-Harbor syndrome. The patient exhibited short stature, developmental language delay, dysmorphic facial features, and early puberty. Targeted exome sequencing revealed a heterozygous mutation, c.7303C>T (p.Arg2435Ter), in the SRCAP gene, confirming a diagnosis of Floating-Harbor syndrome. She responded well to human recombinant growth hormone and gonadotropin-releasing hormone (GnRH) agonist, effectively suppressing bone maturation and improving her height SDS from -4.6 to -2.4.

MicroRNAs as novel biomarkers for the diagnosis and treatment of pediatric diseases.

MicroRNAs (miRNAs) are highly conserved noncoding RNAs that regulate gene expression by silencing or degrading messenger RNAs. Many of the approximately 2,500 miRNAs discovered in humans are known to regulate vital biological processes, including cell differentiation, proliferation, apoptosis, and embryonic tissue development. Aberrant miRNA expression may have pathological and malignant consequences. Therefore, miRNAs have emerged as novel diagnostic markers and potential therapeutic targets for various diseases. Children undergo various stages of growth, development, and maturation between birth and adulthood. It is important to study the role of miRNA expression in normal growth and disease development during these developmental stages. In this mini-review, we discuss the role of miRNAs as diagnostic and prognostic biomarkers in various pediatric diseases.

Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents.

Two-dimensional shear wave elastography (2D-SWE) evaluates liver stiffness using a non-invasive method, but studies in the paediatric population are rare. This study evaluated the role of 2D-SWE in the diagnosis and severity of paediatric non-alcoholic fatty liver disease (NAFLD). In total, 131 patients with NAFLD and 25 healthy controls were enrolled in this study. The diagnosis and severity of NAFLD were initially assessed using the ultrasound fatty liver index (US-FLI), and all participants underwent 2D-SWE. US-FLI semi-quantitatively measures the severity of NAFLD on a scale of 2-8. The assessment of liver stiffness measurement (LSM) by 2D-SWE is presented in kilopascals (kPa). The NAFLD group was characterised by significantly higher LSM (4.40 ± 0.90 kPa) than the control group (3.76 ± 0.28 kPa) (P < 0.001). 2D-SWE significantly correlated with age, height, weight, body mass index, glucose, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, US-FLI, and triglyceride-glucose index (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve of LSM for predicting US-FLI ≥ 2 and ≥ 6 was 0.784 (P < 0.001) and 0.819 (P < 0.001), respectively. In conclusion, we suggest that 2D-SWE can be used as a non-invasive diagnostic tool for diagnosing and assessing the severity of paediatric NAFLD.

Association between uric acid and height during growth hormone therapy in children with idiopathic short stature.

Background: Serum uric acid (UA) within appropriate levels is reported to be beneficial in patients with idiopathic short stature (ISS). This study aimed to evaluate the association between serum UA levels and height standard deviation scores (SDS) in patients with ISS during growth hormone (GH) therapy. Methods: A longitudinal study (LG Growth Study) of 182 children (mean age: 7.29±2.60 years) with ISS was performed. All participants were in the prepubertal stage and treated with GH, and the data within a treatment period of 30 months were analyzed. Results: In the adjusted Pearson's correlation, UA was significantly correlated with height SDS after controlling for sex, age, and body mass index (BMI) SDS (r=0.22, p=0.007). In the adjusted multiple regression analyses, the height SDS was significantly associated with UA after controlling for sex, age, and BMI SDS (ß=0.168, p=0.007). Within the 30-month treatment period, the UA levels significantly increased as the height SDS increased, and the mean UA levels at baseline and 30 months after treatment were 3.90±0.64 mg/dL and 4.71±0.77 mg/dL, respectively (p=0.007). Discussion: In conclusion, UA is related to height SDS, and GH treatment leads to a significant increase in UA without hyperuricemia. Elevated UA is considered a favorable outcome of GH therapy, and further studies are needed to determine its role as a monitoring tool.

Height outcomes in Korean children with idiopathic short stature receiving growth hormone treatment.

Objectives: Growth hormone (GH) therapy's capacity to increase height velocity and height at the end of the study in children with idiopathic short stature (ISS) is controversial. We aimed to investigate the height standard deviation score (SDS) and height velocity of patients with ISS in Korea who received GH treatment. Methods: We retrospectively reviewed and performed linear mixed model and survival analyses on data from 12 tertiary hospitals in Korea, including subjects diagnosed with ISS from January 2009 to September 2019, treated with GH therapy for more than 6 months, and who were at a pre-pubertal state at the time of diagnosis. Results: We included 578 children (330 boys and 248 girls). The mean daily dose of GH in this study was 0.051 mg/kg, which was lower than the approved dose in Korea of 0.062 - 0.067 mg/kg. Height SDS was higher in patients who started treatment before the age of 6 years. The probability of reaching the target SDS (-1 SDS) from the beginning of treatment to 2-3 years after its start was higher in children starting treatment before the age of 6 years. The hazard ratio to reach the target SDS (-1 SDS) when using automatic pen or electronic devices was 1.727 times higher than that when using the needle and syringe device. Conclusion: ISS patients should start GH treatment at an early age, and even lower-than-recommended drug doses may be effective. The selection of automatic pen or electronic device can have a positive effect on reaching the target height SDS.

Exosomal miRNA Profile in Small-for-Gestational-Age Children: A Potential Biomarker for Catch-Up Growth.

Objective: The mechanism underlying postnatal growth failure and catch-up growth in small-for-gestational-age (SGA) children is poorly understood. This study investigated the exosomal miRNA signature associated with catch-up growth in SGA children. Methods: In total, 16 SGA and 10 appropriate-for-gestational-age (AGA) children were included. Serum exosomal miRNA was analyzed using next-generation sequencing (NGS). Exosomal miRNA was profiled for five SGA children with catch-up growth (SGA-CU), six SGA children without CU growth (SGA-nCU), and five AGA children. Results: Exosomal miRNA profiles were clustered into three clear groups. The exosomal miRNA expression profiles of the SGA-nCU group differed from those of the SGA-CU and AGA groups. In all, 22 miRNAs were differentially expressed between SGA-nCU and AGA, 19 between SGA-nCU and SGA-CU, and only 6 between SGA-CU and AGA. In both SGA-nCU and SGA-CU, miR-874-3p was upregulated and miR-6126 was downregulated. Therefore, these two miRNAs could serve as biomarkers for SGA. Compared with SGA-CU and AGA, miR-30c-5p, miR-363-3p, miR-29a-3p, and miR-29c-3p were upregulated in SGA-nCU, while miR-629-5p and miR-23a-5p were downregulated. These six miRNAs could be associated with growth failure in SGA-nCU children. Conclusions: SGA children without CU have a distinct exosomal miRNA expression profile compared with AGA and SGA children with CU. Exosomal miRNAs could serve as novel biomarkers for CU.

A Novel Heterozygous ACAN Variant in a Short Patient Born Small for Gestational Age with Recurrent Patellar Dislocation: A Case Report

ACAN variants can manifest as various clinical features, including short stature, advanced bone age (BA), and skeletal defects. Here, we report rare clinical manifestations of ACAN defects in a 9 year, 5 month-old girl born small for gestational age (SGA), who presented with short stature, and was initially diagnosed with idiopathic growth hormone deficiency. She displayed several dysmorphic features, including genu valgum, cubitus valgus, and recurrent patellar dislocations. She presented with progressive advancement of BA compared with chronological age. Whole exome sequencing confirmed the presence of a novel heterozygous nonsense variant, c.1968C>G, p.(Tyr656*), in ACAN. ACAN variants should be considered in short stature patients born SGA with joint problems, particularly those with recurrent patellar dislocation and genu valgum.

Triglyceride glucose index is superior biomarker for predicting type 2 diabetes mellitus in children and adolescents.

The triglyceride-glucose (TyG) index is associated with predicting type 2 diabetes mellitus (T2DM), but its relationship with homeostatic model assessment of insulin resistance (HOMA-IR) in T2DM is not established. We aimed to investigate the role of TyG index for detection of T2DM in children and adolescents and compare it with HOMA-IR. A cross sectional study was performed in 176 overweight or obese children and adolescents with mean age of 11.34 ± 3.24 years. TyG index was calculated as ln (fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Of a total of 176 subjects, 57 (32%) were diagnosed with T2DM. Significant differences were observed in the TyG index between T2DM and non-T2DM (p < 0.001). The TyG index had a positive correlation with fasting glucose (r = 0.519, p < 0.001), HOMA-IR (r = 0.189, p < 0.017), HbA1c (r = 0.429, p < 0.001), total cholesterol (TC) (r = 0.257, p = 0.001), TG (r = 0.759, p < 0.001), and low-density lipoprotein cholesterol (LDL-C)(r = 0.152, p < 0.001), and a negative correlation with high-density lipoprotein cholesterol (HDL-C)(r = -0.107, p < 0.001) after controlling for sex, age and BMI standard deviation scores (SDS). In multiple regression analyses, 91.8% of the variance in TyG index was explained by age, glucose, HOMA-IR, TG, LDL-C, and HDL-C (p < 0.001). In the receiver operating characteristic (ROC) analysis, the TyG index [area under the curve (AUC) 0.839)] showed a better performance compared to HOMA-IR (AUC 0.645) in identifying patients with T2DM (p < 0.001). In conclusion, the TyG index had significant association with insulin resistance in T2DM and was superior to HOMA-IR in predicting T2DM in children and adolescents.

A population-based study of TyG index distribution and its relationship to cardiometabolic risk factors in children and adolescents.

The purpose of this study was to present age- and sex-specific distributions of the triglyceride-glucose (TyG) index and to evaluate their relationship with cardiometabolic risk factors in children and adolescents. A total of 7404 participants aged 10-18 years from the Korean National Health and Nutrition Survey were included as the reference population. The TyG index was calculated as ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The percentile of the TyG index exhibited a steady linear relationship with age for both sexes. TyG index significantly correlated with waist circumference (WC) standard deviation score (SDS; r = 0.110, p < 0.001), systolic blood pressure (SBP; r = 0.104, p < 0.001), diastolic blood pressure (DBP; r = 0.083, p < 0.001), glucose (r = 0.220, p < 0.001), high-density lipoprotein cholesterol (HDL-C; r = - 0.325, p < 0.001), and triglycerides (TG; r = 0.926, p < 0.001). Multiple linear regression analysis revealed that the TyG index was significantly associated with WC SDS (ß = 0.116, p < 0.001), SBP (ß = 2.009, p < 0.001), DBP (ß = 1.464, p < 0.001), glucose (ß = 3.376, p < 0.001), HDL-C (ß = - 6.431, p < 0.001), and TG (ß = 85.518, p < 0.001). Our results suggest that the TyG index has a steady linear distribution for sex and age in children and adolescents and constitutes an indicator for predicting metabolic disorders that could lead to cardiovascular disease later in life.

Distribution of waist-to-height ratio and cardiometabolic risk in children and adolescents: a population-based study.

This study was performed to evaluate the waist-to-height ratio (WHtR) distribution and assess its relationship with cardiometabolic risk in children and adolescents. A total of 8091 subjects aged 10-18 years were included from a nationally representative survey. Participants were classified into three groups: (1) < 85th, (2) ≥ 85th and < 95th, and (3) ≥ 95th percentile of WHtR. The WHtR distribution varied with sex and age. Whereas WHtR decreased from age 10-15 years in boys and from age 10-12 years in girls, it slightly increased thereafter. Compared to the < 85th percentile group, the WHtR ≥ 85th and < 95th percentile group had an odds ratio (OR) of 1.2 for elevated blood pressure (BP), 1.89 for elevated triglycerides (TGs), 1.47 for reduced high-density lipoprotein cholesterol (HDL-C) and 4.82 for metabolic syndrome (MetS). The ≥ 95th percentile group had an OR of 1.4 for elevated BP, 2.54 for elevated glucose, 2.22 for elevated TGs, 1.74 for reduced HDL-C, and 9.45 for MetS compared to the < 85th percentile group. Our results suggest that sex- and age-specific WHtR percentiles can be used as a simple clinical measurement to estimate cardiometabolic risk.

Gene polymorphisms in leptin and its receptor and the response to growth hormone treatment in patients with idiopathic growth hormone deficiency.

This study aimed to investigate the relationships between genetic polymorphisms of leptin/receptor genes and clinical/biochemical characteristics in children with growth hormone deficiency (GHD). Ninety-three GHD children and 69 age-matched normal controls were enrolled. Anthropometric measurements, bone age, and laboratory test results were obtained. Polymorphisms in the LEP gene promoter locus (LEP-2548, rs7799039) and LEPR genes (K109R, rs1137100 and Q223R, rs1137101) were analyzed using PCR-RFLP. The serum leptin levels were measured using an ELISA kit. The median height and BMI z-scores of all GHD subjects were -2.20 and -0.26, respectively, and those of normal controls were -0.30 and -0.13, respectively. The serum leptin levels were similar between GHD subjects and normal controls (p = 0.537), but those were different between the complete GHD (6.97 ng/mL) and partial GHD (4.22 ng/mL) groups (p = 0.047). There were no differences in the genotypic distributions of LEP-2548, LEPR K109R, and Q223R between GHD subjects and normal controls. However, GHD subjects with the G allele at LEP-2548 showed higher IGF-1 (p = 0.047) and IGFBP-3 SDSs (p = 0.027) than GHD subjects with the A allele. GHD subjects with the G allele at LEPR Q223R showed lower stimulated GH levels (p = 0.023) and greater height gain after 1 year of GH treatment (p = 0.034) than GHD subjects with the A allele. In conclusion, leptin/leptin receptor genes are suggested to have the role of growth-related factors, which can affect various growth responses in children who share the same disease entity.

Mild Phenotype of Xq Deletion and 3q Duplication Associated with der(X)t(X;3)(q21.1;q22.1) without Loss of XIST Gene.

We report a 10-year-old female patient with der(X)t(X;3)(q21.1;q22.1), resulting in 3q duplication and Xq deletion. The main clinical feature was primary ovarian failure and there was no abnormal phenotype corresponding to 3q duplication syndrome. This might be explained by the XIST gene at the X-inactivation center on Xq13.2, which was not deleted in this case. The conventional karyotyping was preliminarily reported as 46,X,inv(X) (q13q26) due to the similar banding patterns of Xq13.2-q24 and 3q25.33-q29. This case highlights the value of using a chromosomal microarray as a clinical diagnostic test for individuals with developmental delay or congenital anomalies.

Microdeletion in the IGF-1 receptor gene of a patient with short stature and obesity: a case report.

OBJECTIVES: Defects in the IGF-1 receptor gene (IGF1R) induce IGF-1 resistance, characterized by intrauterine and postnatal growth retardation, normal or elevated serum IGF-1 levels, and feeding problems. Obesity, idiopathic growth hormone deficiency (IGHD), bone age advancement, and serum IGF-1 level in the lower half of the reference range are very rare clinical features in patients with IGF1R defects. CASE PRESENTATION: In this study, we report the atypical clinical manifestations of IGF1R defects. Short stature girl born small for gestational age were initially diagnosed with IGHD. No catch-up growth was achieved despite sufficiently elevated IGF-1 levels after recombinant human growth hormone (rhGH) treatment. Single nucleotide polymorphism microarray analysis finally confirmed terminal deletion of 15q26.2q26.3 in the subject. CONCLUSION: Intrauterine growth retardation, postnatal growth failure, and IGF-1 resistance during rhGH treatment are homologous features exhibited by affected patients, and may be predictive of IGF1R defects.

Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty.

OBJECTIVES: Makorin ring finger protein 3 (MKRN3) is associated with the initiation of puberty, and loss of function mutation of MKRN3 is the most common genetic cause of central precocious puberty (CPP). A recent study reported that MKRN3 interacts with and suppresses neural pentraxin-1 precursor (NPTX1) activity via polyubiquitination during early puberty in the mouse hypothalamus. This study investigated the correlation between serum NPTX1 and MKRN3 in CPP girls and predicted the potential role of NPTX1 in pubertal progression. METHODS: In this case-control study, we examined 34 girls diagnosed with CPP and 34 healthy prepubertal girls. Anthropometric and hormonal parameters were measured and serum levels of NPTX1 and MKRN3 were evaluated with commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum MKRN3 level decreased significantly in CPP patients compared to controls (344.48 ± 333.77 and 1295.21 ± 780.80 pg/mL, respectively, p<0.001). Serum MKRN3 tended to decrease as Tanner breast stage increased. However, no significant difference was observed in serum NPTX1 levels between patients and controls (20.14 ± 31.75 ng/mL and 12.93 ± 8.28 ng/mL, respectively, p=0.248). The serum level of NPTX1 did not change significantly with the Tanner breast stage. Serum NPTX1 was correlated with the height standard deviation score (r=0.255; p<0.05), but was not correlated with serum MKRN3 level or the others. Conclusion: Although serum NPTX1 level was independent of serum MKRN3 level, the possibility they might be involved in the progression of puberty or CPP remains. Further research is needed to determine their role in the hypothalamus.

2017 Clinical practice guidelines for dyslipidemia of Korean children and adolescents.

The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.

Body mass index trajectories and adiposity rebound during the first 6 years in Korean children: Based on the National Health Information Database, 2008-2015.

PURPOSE: We analyzed the nationwide longitudinal data to explore body mass index (BMI) growth trajectories and the time of adiposity rebound (AR). METHODS: Personal data of 84,005 subjects born between 2008 and 2012 were obtained from infant health check-ups which were performed at 5, 11, 21, 33, 45, 57, and 69 months. BMI trajectories of each subject were made according to sex and the timing of AR, which was defined as the lowest BMI occurred. Subjects were divided according to birth weight and AR timing as follows: very low birth weight (VLBW), 0.5 kg ≤ Bwt ≤ 1.5 kg; low birth weight (LBW), 1.5 kg < Bwt ≤ 2.5 kg; non-LBW, 2.5 kg < Bwt ≤ 5.0 kg; very early AR, before 45 months; early AR, at 57 months; and moderate-to-late AR, not until 69 months. MAIN RESULTS: Median time point of minimum BMI was 45 months, and the prevalence rates of very early, early, and moderate-to-late AR were 63.0%, 16.6%, and 20.4%, respectively. BMI at the age of 57 months showed a strong correlation with AR timing after controlling for birth weight (P < 0.001). Sugar-sweetened beverage intake at 21 months (P = 0.02) and no-exercise habit at 57 months (P < 0.001) showed correlations with early AR. When VLBW and LBW subjects were analyzed, BMI at 57 months and breastfeeding at 11 months were correlated with rapid weight gain during the first 5 months (both P < 0.001). CONCLUSIONS: Based on this first longitudinal study, the majority of children showed AR before 57 months and the degree of obesity at the age of 57 months had a close correlation with early AR or rapid weight gain during infancy.

Relationship between growth velocity and change of levels of insulin-like growth factor-1, insulin-like growth factor binding protein-3 and, IGFBP-3 promoter polymorphism during GnRH agonist treatment.

PURPOSE: This study aims to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) on the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis and to evaluate whether -202 A/C IGF binding protein-3 (IGFBP-3) promoter polymorphism affects growth velocity in females with central precocious puberty (CPP) during treatment. METHODS: Data was collected from 97 females younger than 9 years, diagnosed with precocious puberty and treated with GnRHa for at least 1 year at Kangdong Sacred Heart Hospital from 2014 to 2015. Their body height, weight, change in height standard deviation score (∆SDS), serum IGF-1, serum IGFBP-3, bone age, and -202 A/C IGFBP-3 promoter polymorphism were measured before and after GnRHa treatment. The interrelationships between the variables were calculated. RESULTS: During treatment, height SDS, IGF-1 SDS, IGFBP-3 SDS, and IGF-1/IGFBP-3 ratio significantly decreased. A significant correlation was observed between ∆IGF-1 SDS and ∆height SDS (r=0.405, P<0.001). The presence of the C allele was significantly correlated with IGF-1 SDS after treatment (P=0.049) and with IGFBP-3 SDS before and after treatment (P=0.012 and P=0.001), but not with ∆IGF-1 SDS, ∆IGFBP-3 SDS, ∆IGF-1/IGFBP-3 ratio, or ∆height SDS. CONCLUSION: Growth velocity during GnRHa treatment is related to ∆IGF-1 SDS, indicating the apparent impact of GnRHa on the GH-IGF-1 axis. The -202 A/C IGFBP-3 promoter polymorphism does not affect the growth velocity of GnRHa in CPP girls.