2022 Clinical practice guidelines for central precocious puberty of Korean children and adolescents

The Committee of Central Precocious Puberty of Korean Pediatrics and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based 2022 clinical practice guidelines for central precocious puberty in Korean children and adolescents. These guidelines provide the grade of recommendations, which includes both the strength of recommendations and the level of evidence. In the absence of sufficient evidence, recommendations are based on expert opinion. These guidelines have been revised and supplement the previous guidelines "Clinical Guidelines for Precocious Puberty 2011," and are drawn from a comprehensive review of the latest domestic and international research and the grade of recommendation appropriate to the domestic situation. This review summarizes the newly revised guidelines into 8 key questions and 27 recommendations and consists of 4 sections: screening, diagnosis, treatment, and long-term outcome of central precocious puberty.

Brain magnetic resonance imaging (MRI) findings in central precocious puberty patients: is routine MRI necessary for newly diagnosed patients?

Purpose@#The overall incidence of central precocious puberty (CPP) has increased in recent decades, and brain magnetic resonance imaging (MRI) evaluations are recommended in cases of suspected brain lesions. This study aimed to investigate the prevalence of MRI abnormalities and to evaluate the need for routine brain MRI in patients with newly diagnosed CPP. @*Methods@#This retrospective study reviewed the data of patients newly diagnosed with CPP who underwent routine pituitary MRI at Korea University Anam Hospital from March 2020 to September 2021. A total of 199 girls and 24 boys was enrolled in this study. Positive MRI findings were categorized as abnormal pituitary, nonpituitary incidental, and pathological. In addition, we investigated the incidence of MRI abnormalities and evaluated their associations with clinical and biochemical factors. @*Results@#Positive brain MRI findings were observed in 84 patients (37.7%). Pituitary abnormalities were found in 54 patients (24.2%), with Rathke cleft cysts being the most common (16.1%). Incidental nonpituitary findings were observed in 29 patients (13.0%), while a pathological brain lesion (diagnosed as hypothalamic hamartoma) was observed in only 1 female patient (0.4%). No significant differences in sex or age were found in incidence of pituitary abnormalities or nonpituitary incidental findings. Compared with headache controls, significant associations were observed between abnormal pituitary findings on MRI and CPP (unadjusted odds ratio, 3.979; 95% confidence interval, 1.726–9.173). @*Conclusion@#True pathological findings were rare, even though the prevalence of abnormalities on pituitary MRI in patients with CPP was relatively high. Considering its cost-effectiveness, MRI screenings should be carefully considered in patients with CPP.

Comparison of Initial Presentation of Pediatric Diabetes Before and During the Coronavirus Disease 2019Pandemic Era

Background@#Hospital visitation has become challenging during the coronavirus disease 2019 pandemic because of quarantine measures and fear of infection. Consequently, newly diagnosed patients may present with more severe diseases during the pandemic. The present study analyzed the differences in the initial clinical presentations of newly diagnosed patients with type 1 diabetes (T1D) and type 2 diabetes (T2D), comparing pre-pandemic and pandemic periods. @*Methods@#Newly diagnosed patients with T1D or T2D and aged < 18 years during 2018–2020 were included in the study. Data were collected retrospectively from four academic centers in Gyeonggi-do, South Korea. Initial clinical data were compared between the pre-pandemic (2018–2019) and pandemic (2020) periods. @*Results@#In the pre-pandemic and pandemic periods, 99 patients (41 T1D and 58 T2D patients) and 84 patients (51 T1D and 33 T2D patients) were identified, respectively. During the pandemic, the proportion of diabetic ketoacidosis (DKA) cases increased compared to the pre-pandemic period (21.2% during 2018–2019 vs. 38.1% in 2020; P = 0.012). In the prepandemic and pandemic periods, initial pH was 7.32 ± 0.14 and 7.27 ± 0.15, respectively (P = 0.040), and HbA1c values were 11.18 ± 2.46% and 12.42 ± 2.87%, respectively (P = 0.002). During the pandemic, there was an increased risk of DKA in patients with T1D (odds ratio, 2.42; 95% confidence interval, 1.04–5.62; P = 0.040). @*Conclusion@#During the pandemic, the proportion of DKA in newly diagnosed patients with T1D increased and clinical parameters showed a deteriorating pattern. Increased awareness of pediatric diabetes, especially DKA, could facilitate visit to the hospital for an early diagnosis; thus, reducing the number of DKA cases during the pandemic era.

Management of severe pediatric obesity

Pediatric obesity has increased over the decades, and in particular, severe pediatric obesity has become a serious public health problem. A concern has arisen that the COVID-19 pandemic may exacerbate the incidence of childhood obesity.Current Concepts: The consequences of severe pediatric obesity are more devastating than those of moderate obesity. Children with severe obesity are at a greater risk for hypertension, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, atherosclerosis, and adult obesity. Correct assessment and diagnosis of a child with severe obesity is key to successful therapy. A thorough history and physical examination are important in identifying monogenic obesity or metabolic syndrome. Eating behaviors and psychosocial factors should be assessed to improve weight management outcomes. Treatment options for severe pediatric obesity include lifestyle modification, pharmacotherapy, and metabolic and bariatric surgery. Even though progress has been made with regard to the treatment of obesity, safe and effective treatment of severe pediatric obesity is challenging.Discussion and Conclusion: More efforts and innovations are needed to find a solution for the huge medical and emotional burden the children with severe obesity and their families are enduring.

Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center

Background@#Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available.This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP. @*Methods@#A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy. @*Results@#The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline (P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively (P = 0.481). @*Conclusion@#This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP.

Management of severe pediatric obesity

Pediatric obesity has increased over the decades, and in particular, severe pediatric obesity has become a serious public health problem. A concern has arisen that the COVID-19 pandemic may exacerbate the incidence of childhood obesity.Current Concepts: The consequences of severe pediatric obesity are more devastating than those of moderate obesity. Children with severe obesity are at a greater risk for hypertension, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, atherosclerosis, and adult obesity. Correct assessment and diagnosis of a child with severe obesity is key to successful therapy. A thorough history and physical examination are important in identifying monogenic obesity or metabolic syndrome. Eating behaviors and psychosocial factors should be assessed to improve weight management outcomes. Treatment options for severe pediatric obesity include lifestyle modification, pharmacotherapy, and metabolic and bariatric surgery. Even though progress has been made with regard to the treatment of obesity, safe and effective treatment of severe pediatric obesity is challenging.Discussion and Conclusion: More efforts and innovations are needed to find a solution for the huge medical and emotional burden the children with severe obesity and their families are enduring.

Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center

Background@#Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available.This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP. @*Methods@#A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy. @*Results@#The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline (P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively (P = 0.481). @*Conclusion@#This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP.

Prevalence of idiopathic scoliosis in girls with central precocious puberty: effect of a gonadotropin-releasing hormone agonist

Purpose@#Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis and occurs in children between 10 to 18 years old, during periods of growth spurts and puberty changes. In patients with central precocious puberty (CPP), due to early growth spurt, AIS is expected to develop before 10 years of age. Both AIS and CPP are more common in girls than in boys. The aim of this study was to determine the prevalence of AIS in girls with CPP and to evaluate the effect of treatment with gonadotropin-releasing hormone (GnRH) agonists on progression of scoliosis in these patients. @*Methods@#We retrospectively reviewed medical records of 553 girls, 338 with CPP and 215 without CPP. Scoliosis angle was measured on the standing frontal radiograph of each patient according to the Cobb method. Patients with a Cobb angle of 10° or more were diagnosed with scoliosis. For girls with CPP, followup spine radiographs were collected 1 year after treatment with GnRH agonists. Progression of scoliosis before and after treatment was compared in terms of Cobb angle changes. @*Results@#AIS was more prevalent in girls that were affected by CPP compared tocontrols without CPP (11.5% vs. 6.0%, CPP girls vs. non-CPP girls, respectively, P=0.031). The peak serum luteinizing hormone level positively correlated with Cobb angle (R2=0.015, P=0.023) in the CPP group. No progression of scoliosis was observed in CPP girls after one year of GnRH agonist treatment. Additionally, the prevalence of scoliosis decreased in CPP girls after 1 year of the treatment. @*Conclusion@#We report that the prevalence of AIS is higher in girls with CPP than in non-CPP patients. A regular follow-up schedule for spine radiographs should be considered to reduce the risk of progression. Furthermore, GnRH agonist treatment for CPP may have a suppressive effect on progression of AIS.

Serum osteocalcin levels in overweight children

PURPOSE: Bone plays a role in glucose metabolism through the release of uncarboxylated osteocalcin into the systemic circulation. The identified novel roles for osteocalcin include increasing insulin secretion and sensitivity, energy expenditure, reduction of fat mass, and mitochondrial proliferation and functional enhancement. This study aimed to determine serum osteocalcin levels in overweight children and to investigate the relationships of osteocalcin with glucose metabolism and insulin sensitivity. METHODS: After overnight fasting, serum osteocalcin levels were measured in overweight (n=50) children between 6.0 and 12.9 years of age and nonoverweight controls (n=60). Height, weight, fasting serum glucose, insulin, alkaline phosphatase, total cholesterol, and 25 hydroxy vitamin D₃ (25(OH)VitD₃) were also measured in all subjects. RESULTS: There were significant differences in serum osteocalcin levels between the overweight and control groups (64.00±20.44 vs. 89.56±28.63, P<0.001). Serum osteocalcin levels were inversely correlated with body mass index (BMI) (r=-0.283, P=0.003), weight standard deviation score (SDS) (r=-0.222, P=0.020), BMI SDS (r=-0.297, P=0.002), insulin (r=-0.313, P=0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) index (r=-0.268, P=0.005). In the subsequent multiple regression analyses, BMI, HOMA-IR, and age were determined to be independent predicting factors for serum osteocalcin. CONCLUSIONS: Our findings showed associations of serum osteocalcin with glucose metabolism and insulin sensitivity in overweight children, but we could not establish a causal relationship.

Thyroid function in girls with central precocious puberty

PURPOSE: Obesity is a well-known risk factor for central precocious puberty (CPP). Recently, elevated thyroid stimulating hormone (TSH) was reported in obese youth. However, few data regarding the relationship between CPP and TSH are available. The aim of this study was to evaluate thyroid function in girls with CPP and the relationship between CPP and serum TSH concentration. METHODS: This was a retrospective cross-sectional study. A total of 1,247 girls aged between 6.0 and 8.9 years who had undergone a gonadotropin-releasing hormone (GnRH) stimulation test to determine the presence of puberty were studied. Subjects were classified into CPP (n=554) and non-CPP (n=693) groups according to the results of the GnRH stimulation test. Characteristics and laboratory data of the CPP and non-CPP groups were compared and correlations between those characteristics and laboratory data and TSH concentration were evaluated. Serum TSH concentration in the CPP group was higher than that of the non-CPP group (3.19±1.55 mIU/L vs. 2.58±1.34 mIU/L, P<0.001). RESULTS: Serum free thyroxine (fT4) concentration in the CPP group was notably lower than that of the non-CPP group (1.38±0.14 ng/dL vs. 1.44±0.18 ng/dL, P<0.001). Across all subjects, 149 girls (11.9%) had hyperthyrotropinemia. The prevalence of hyperthyrotropinemia was higher in the CPP group compared to the non-CPP group (15.7% vs. 8.9%, P<0.001). TSH concentrations were positively correlated with age, height, weight, BMI, bone age, bone age advance, insulin-like growth factor 1 (IGF-1), IGF-1 standard deviation score, basal luteinizing hormone (LH), peak LH and basal follicle-stimulation hormone. TSH concentrations were negatively correlated with fT4. Multiple linear regression analysis showed that age (β=0.548, P<0.001) and peak LH (β=0.019, P=0.008) were independently associated with serum TSH concentration. CONCLUSIONS: Hyperthyrotropinemia in girls with CPP tends to be associated with pubertal LH elevation. In conclusion, pubertal onset may be associated with thyroid function.

HbA1c Cutoff for Prediabetes and Diabetes Based on Oral Glucose Tolerance Test in Obese Children and Adolescents

BACKGROUND: Oral glucose tolerance test (OGTT) is a traditional diagnostic tool for diabetes. Hemoglobin A1c (HbA1c) is an alternative method used in adults; however, its application in youths has been controversial. We evaluated the diagnostic performance of HbA1c and determined optimal cutoff points for detecting prediabetes and diabetes in youth. METHODS: This retrospective study included 389 obese children (217 boys, 55.8%) who had undergone simultaneous OGTT and HbA1c testing at six hospitals, Korea, between 2010 and 2016. Subjects were diagnosed with diabetes (fasting glucose ≥ 7.0 mmol/L; 2-hour glucose ≥ 11.1 mmol/L) or prediabetes (fasting glucose 5.6–6.9 mmol/L; 2-hour glucose 7.8–11.0 mmol/L). The diagnostic performance of HbA1c for prediabetes and diabetes was determined using the area under the receiver operating characteristic curve (AUC). RESULTS: At diagnosis, 197 (50.6%) subjects had normoglycemia, 121 (31.1%) had prediabetes, and 71 (18.3%) had diabetes. The kappa coefficient for agreement between OGTT and HbA1c was 0.464. The optimal HbA1c cutoff points were 5.8% (AUC, 0.795; a sensitivity of 64.1% and a specificity of 83.8%) for prediabetes and 6.2% (AUC, 0.972; a sensitivity of 91.5% and a specificity of 93.7%) for diabetes. When HbA1c (≥ 6.2%) and 2-hour glucose level were used to diagnose diabetes, 100% were detected. CONCLUSION: Pediatric criteria for HbA1c remain unclear, therefore, we recommend the combination of fasting and 2-hour glucose levels, in addition to HbA1c, in the diagnosis of childhood prediabetes and diabetes.

Comparison of postnatal catch-up growth according to definitions of small for gestational age infants / 소아과

PURPOSE: Small for gestational age (SGA) is confusingly defined as birth weight (BW) either below 3rd percentile or 10th percentile for infants. This study aimed to compare postnatal catch-up growth between SGA groups according to different definitions. METHODS: Data of 129 infants born with BW below the 10th percentile and admitted to Korea University Anam Hospital and Ansan Hospital were retrospectively reviewed. Height and weight were measured at 6, 12, and 24 months. Results were compared between group A (BW: <3rd percentile) and group B (BW: 3rd–10th percentile). RESULTS: Group A included 66 infants and group B included 63. At age 6 months (n=122), 62.9% of group A and 71.7% (P=0.303) of group B showed catch-up growth in weight. At 6 months (n=69), 55.9% of group A and 80.0% of group B (P<0.05) showed catch-up growth in height. At 12 months (n=106), 58.5% of group A, and 75.5% (P=0.062) of group B showed catch-up growth in weight. At 12 months (n=75), 52.8% of group A and 64.1% of group B (P=0.320) showed catch-up growth in height. Up to age 24 months, 66.7%/80.0% in group A and 63.6%/80.0% in group B showed catch-up growth in weight/height. CONCLUSION: Despite different definitions, there were no significant differences between the two SGA groups in postnatal catch-up growth up to age 24 months, except for height at 6 months. Compared to infants with appropriate catch-up growth, low gestational age and BW were risk factors for failed catch-up growth at 6 months.

Low levels of 25-hydroxyvitamin D in children and adolescents with type 1 diabetes mellitus: a single center experience

PURPOSE: Low vitamin D level is common in adults with diabetes mellitus (DM). We assessed vitamin D level and its associated factors in Korean youth with type 1 DM. METHODS: Type 1 DM cases (n=85) and healthy controls (n=518) aged < 20 years were included and grouped into 3 categories according to vitamin D level: deficiency ( < 20 ng/mL), insufficiency (20–30 ng/mL), or sufficiency (≥30 ng/mL). RESULTS: The mean serum vitamin D level was significantly lower (21.6±8.5 ng/mL vs. 28.0±12.0 ng/mL, P < 0.001) and vitamin D deficiency prevalence was significantly higher (48% vs. 26%, P < 0.001) in type 1 DM cases than in healthy controls. Logistic regression analysis revealed that type 1 DM cases were more likely to have vitamin D deficiency (P=0.004), independent of sex, age, and body mass index. Type 1 DM cases with vitamin D deficiency/insufficiency were mainly diagnosed in winter (November to April) (P=0.005), and the duration of diabetes was longer than in those with vitamin D sufficiency (P=0.046). However, season of diagnosis, duration of diabetes, prescribed daily insulin dose, and glycosylated hemoglobin and C-peptide levels were not associated with 25-hydroxyvitamin D (25(OH)D) level in type 1 DM cases after adjustment for other factors. CONCLUSIONS: We recommend assessment of serum 25(OH)D level in type 1 DM cases and to treatment if findings indicate insufficiency. Further studies investigating the mechanisms underlying vitamin D deficiency in youth with type 1 DM are needed.

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.

Treatment outcomes of gonadotropin-releasing hormone agonist in obese girls with central precocious puberty

PURPOSE: This study investigated the influence of obesity on the clinical course and effect of gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP). METHODS: Medical records of 182 girls with CPP treated with GnRHa were reviewed. They were divided into 2 groups: normal weight (n=108) and overweight/obesity (n=74). Chronological age (CA), bone age (BA), difference between BA and CA (BA–CA), standard deviation score (SDS) of height, body mass index (BMI), predicted adult height (PAH), and laboratory findings were compared at baseline, after 1 year, and at the end of GnRHa treatment in both groups. RESULTS: Mean BMI SDS at baseline was 0.08±0.60 in the normal weight group and 1.55±0.36 in the overweight/obesity group. Initial CA, BA, midparental height, and PAH were similar between the 2 groups. BA–CA after treatment was significantly decreased compared to baseline in both groups (P < 0.001). Between the 2 groups, a decrease in BA–CA during treatment showed no significant difference. PAH at the end of treatment was significantly increased compared to baseline in both groups (P < 0.001). PAH at the end of treatment in the overweight/obesity group (159.88±3.41 cm) was similar to that of the normal weight group (159.19±3.25 cm). Comparing the 2 groups according to change in BMI after treatment, there were no differences in ΔPAH, ΔBA–CA, and Δheight SDS for BA. CONCLUSIONS: GnRHa treatment in obese girls with CPP improved the height outcome and had similar results in normal weight CPP girls. Obesity might not affect the efficacy of GnRHa in girls with CPP.

Serum Anti-Müllerian Hormone Levels in Precocious Puberty Girls according to Stage of GnRH Agonist Treatment

Few studies have investigated the long-term effects of gonadotropin-releasing hormone (GnRH) agonist treatment on the reproductive function of central precocious puberty (CPP) girls. In this cross-sectional study, we assessed the ovarian function by analyzing the serum anti-Müllerian hormone (AMH) levels of CPP girls. Our study included 505 CPP girls subdivided into 5 groups according to the GnRH agonist treatment stage: group A (before treatment, n = 98), group B (3 months after initiation, n = 103), group C (12 months after initiation, n = 101), group D (24 months after initiation, n = 101), and group E (6 months after discontinuation, n = 102). We compared the serum AMH levels of the CPP girls with those of 100 bone age-matched controls (before treatment: n = 55; after discontinuation: n = 45). At baseline, the mean AMH level of the CPP girls was 5.9 ± 3.6 ng/mL. The mean AMH level after 3 months of the GnRH agonist treatment was lower (4.7 ± 3.2 ng/mL, P = 0.047) than that at baseline and recovered after 12 months of treatment. Six months after discontinuation, the AMH levels were similar to those at pre-treatment. Before and after the GnRH agonist treatment, the AMH levels were similar to those of the bone age-matched controls. In the precocious puberty girls, the AMH levels based on the GnRH agonist treatment stage were all within the normal reference range. The results of this study suggest that GnRH agonist treatment has no adverse effects on the reproductive function.

Genetic Variations of the KISS1R Gene in Korean Girls with Central Precocious Puberty

The timing of puberty onset varies greatly among individuals, and much of this variation is modulated by genetic factors. This study aimed to identify the kisspeptin receptor (KISS1R) gene variations and to investigate the associations between these variations and central precocious puberty (CPP). Korean girls with CPP (n = 194) and their healthy controls (n = 99) were included in this study. The entire coding region and the exon-intron boundaries (exon 1 through 5) of the KISS1R gene were directly sequenced. Seven polymorphisms were identified in the KISS1R gene. A missense change c.1091T>A, and an intron variant c.738+64G>T showed significantly higher allele frequencies in CPP patients than in controls (c.1091T>A: 30.7% vs. 22.2%, P = 0.031; c.738+64G>T: 45.6% vs. 35.9%, P = 0.023). The missense variant (c.1091T>A) was a nonsynonymous polymorphism that induces amino acid substitution of p.Leu364His. The haplotype CAGTGTC was detected more frequently in the CPP group (P = 0.042). The sequence variants of the KISS1R gene can be inducible factors in the development of CPP. The association between sequence variants and CPP should be validated by further evidence obtained from larger samples of children with CPP.

Physical Activity Measurements with a Pedometer in the Fun and Run Health Camp for Children

BACKGROUND: Obesity in children emerged as a serious problem, and an increase in exercise and a decrease in sedentary activity are important to preventing obesity in children. This study aimed to evaluate the difference in physical activity between the overweight and control groups and whether the activity difference is related to the program provided. METHODS: This study included one-hundred fifty five children who participated in the Fun and Run Health Champ from June 2013 to October 2015. The Health Camp program consisted of lectures in the morning and exercise in the afternoon in 2013 and 2014 (program 1). The morning program in 2015 was changed to Exercise (program 2). The participants were categorized according to their BMI z-score into either the overweight (BMI z-score ≥1) group or the control group (BMI z-score <1). Physical activity was measured with a pedometer. RESULTS: The overweight group had 83 children (53.6%) and the control group had 72 (46.4%). The mean height z-score, weight z-score, and BMI z-score were higher in the overweight group than in the control group. The number of steps per hour in the exercise program (1,561) was greater than for the lecture program (456) (P<0.0001). After the change from lecture to exercise, the number of steps per hour increased significantly (P<0.0001). A greater change in physical activity according to the provided program was observed in the overweight group (overweight-1,033, control-686, P<0.007). CONCLUSION: This study suggests that a designed program considering physical activity could lead to a greater change in physical activity in overweight children. It is necessary to develop the program so that it is fun for children.

Letter: Relationship between Abdominal Obesity and Proportion of Supper and Late-night Meals (Korean J Obes 2016;25:92-8)

No abstract available.

Diabetic Ketoacidosis with Hyperglycemic Hyperosmolar State at the Onset of Type 2 Diabetes Mellitus in an Adolescent Male

A hyperglycemic hyperosmolar state is usually associated with type 2 diabetes. It has significant mortality and morbidity and is rare in the pediatric population. We describe a rare case of a 15-year-old boy with type 2 diabetes who presented to the emergency department with a mixed hyperglycemic hyperosmolar state and diabetic ketoacidosis. Excessive consumption of high-sugar carbonated drinks may have worsening the initial presentation. The patient recovered without any complications. We highlight the fact that gradual correction of osmolarity and sodium is important to avoid cerebral edema despite severe dehydration.