Waist-height ratio and body mass index as indicators of obesity and cardiometabolic risk in Korean children and adolescents.

PURPOSE: We assessed the clinical relevance of waist-height ratio (WHtR) as an indicator of cardiometabolic risk and body fat mass measured by dual-energy x-ray absorptiometry (DXA) among Korean children and adolescents. METHODS: Data from 1,661 children and adolescents aged 10-18 years who participated in the Korea National Health and Nutrition Examination Survey were analyzed. Unadjusted Pearson correlation, age- and sex-adjusted Pearson correlation, and multiple linear regression analyses were performed to investigate the relationships between WHtR standard deviation score (SDS) and cardiometabolic risk factors, as well as DXA-assessed parameters. RESULTS: WHtR SDS was correlated with cardiometabolic risk factors, including systolic blood pressure, glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol, as well as DXA-assessed parameters such as lean mass SDS, fat mass SDS, and fat mass percentage SDS in both whole body and trunk using an adjusted Pearson correlation analyses among all participants (p<0.001). WHtR SDS was strongly correlated with whole-body fat mass and trunk fat mass (r=0.792, p<0.001 and r=0.801, p<0.001, respectively) whereas WHtR SDS had a low correlation coefficient with whole-body lean mass and trunk lean mass SDS (r=0.512, p<0.001 and r=0.487, p<0.001, respectively). In multiple linear regression analyses, WHtR SDS was significantly associated with whole-body and trunk fat mass after adjustment for confounders. CONCLUSION: Cardiometabolic risk factors and body fat mass assessed by DXA in Korean children and adolescents were highly correlated with WHtR. Additionally, WHtR has an advantage in distinguishing fat-free mass. WHtR can be a useful and convenient clinical indicator of cardiometabolic risk factors.

Ectopic lingual thyroid with subclinical hypothyroidism in children.

OBJECTIVES: Lingual thyroid is a rare condition that affects approximately 1 in 100,000 individuals. Although it is usually detected in the pediatric population through newborn screening tests or evaluation of congenital hypothyroidism, there are cases in which it remains undetected until adulthood or until symptoms arise because of glandular enlargement. The possible symptoms of lingual thyroid include foreign body sensation in the throat, dysphagia, dyspnea, and hemorrhage. Several cases of lingual thyroid are asymptomatic and accompanied by subclinical hypothyroidism. Herein, we present three cases of lingual thyroid treated with thyroid hormone suppressive therapy. CASE PRESENTATION: The three patients sought medical attention because of a sore throat or foreign body sensation in the throat. Their newborn screening tests and developmental histories were normal. These patients exhibited subclinical hypothyroidism and were treated with hormone suppression therapy. CONCLUSIONS: Patients with lingual thyroid frequently exhibit subclinical hypothyroidism. Hormone treatment may help to reduce the size of the ectopic thyroid and improve symptoms. If an increase in size is noted during follow-up or symptoms do not improve, surgical treatments may be considered.

Clinical course of peripheral precocious puberty in girls due to autonomous ovarian cysts.

OBJECTIVE: Peripheral precocious puberty (PPP) is the precocious development of secondary sexual characteristics without pulsatile gonadotropin-releasing hormone (GnRH) secretion. In girls, PPP suggests a hyper-oestrogenic state, such as autonomous ovarian cysts and McCune-Albright syndrome (MAS). We aimed to investigate PPP in girls with ovarian cysts, with or without MAS. DESIGN: A retrospective study design was used. PATIENTS AND MEASUREMENTS: The study included 12 girls diagnosed with ovarian cysts with PPP between January 2003 and May 2022. Pelvic sonography was performed in cases of vaginal bleeding or areolar pigmentation in PPP. The clinical characteristics, clinical course and pelvic sonographic findings of girls with ovarian cysts were investigated. RESULTS: We found 18 episodes of ovarian cysts in the 12 girls. The median size of the ovarian cysts was 27.5 mm. Five of the girls were diagnosed with MAS. The median time to spontaneous regression was 6 months. Later, 4 out of 12 girls progressed to central precocious puberty (CPP), and three of them had a recurrence of ovarian cysts. Compared to the non-recurrent and recurrent groups, there was a difference in peak luteinizing hormone (LH) in the GnRH stimulation test and period to cyst regression. CONCLUSIONS: Most ovarian cysts in PPP spontaneously disappear. However, this could be one of the findings of MAS. Some girls progress from PPP to CPP. Therefore, follow-up is necessary for ovarian cysts in patients with PPP. The recurrence of ovarian cysts may occur when spontaneous regression is prolonged.

Effect of gonadotropin-releasing hormone agonist monotherapy and combination therapy with growth hormone on final adult height in girls with central precocious puberty.

This study aimed to compare clinical parameters, including final adult height (FAH), in girls with central precocious puberty treated with gonadotropin-releasing hormone agonists (GnRHa) with and without growth hormone (GH). This retrospective study reviewed data of 210 girls with precocious puberty who had reached FAH in a long-term trial of GnRHa treatment. The subjects were divided into the GnRHa treatment group (n = 188), and the combined GnRHa + GH treatment group (n = 22). Chronological age, bone age, height, height standard deviation score, predicted adult height (PAH), FAH, Tanner stage, and hormone levels were assessed during the treatment period. At the start of treatment, PAH was 156.35 ± 6.34 cm in the GnRHa monotherapy group and 150.41 ± 5.32 cm in the GnRHa + GH group (P < 0.001). At the end of treatment, PAH was 166.25 ± 5.26 cm in the GnRHa group and 164.07 ± 4.99 cm in the combined GnRHa + GH treatment group, which had increased compared to the start of treatment. The FAH in the GnRHa group and GnRHa + GH combination group were 161.07 ± 4.78 cm and 159.63 ± 3.8 6 cm, respectively, without significant difference. In addition, the height gain (FAH-PAH) was significantly higher in the GnRHa + GH group than the GnRHa group (9.22 ± 6.03 cm vs. 4.72 ± 5.01 cm, P < 0.001). In girls with central precocious puberty, the height gain in the FAH compared to PAH at the start of treatment was significantly higher with the GnRHa + GH combination treatment.

Association of serum uric acid Levels with metabolic syndromes in Korean adolescents.

Introduction: The study findings investigated uric acid reference values and their association with a cluster of cardiometabolic risk factors among adolescents using the Korea National Health and Nutrition Examination Survey (KNHANES). Methods: A retrospective cross-sectional study was conducted using the KNHANES database from 2016 to 2018, involving a total of 2,462 participants aged between 10 and 18 years. Based on age- and sex-specific percentile curves for serum uric acid (SUA) levels from the KNHANES, we examined the correlation between cardiometabolic risk factors and serum uric acid levels. Results: The percentile values of SUA varied with sex and age. In male subjects, SUA levels tended to increase from 10 to 14 years of age and plateaued after 14 years of age. Moreover, the overall uric acid level in females was found to be lower than that in males; the levels tended to increase at approximately 10 to 12 years old but were relatively consistent according to age. Mean uric acid levels increased according to obesity status in both males and females. However, correlation analysis revealed that SUA levels were associated with several metabolic risks even after adjusting for obesity. The detailed metabolic syndrome (MetS) components that were observed to be associated with an increase in uric acid levels were different between males and females, but overall, high uric acid levels increased MetS risk. Additionally, a significant increase in MetS-related odds ratio (OR) for components, including waist circumference (WC), triglyceride (TG) levels, and low high-density lipoprotein cholesterol (HDL-c), was observed. However, differences between sexes were apparent, with a more pronounced increase in OR based on SUA levels in girls. Discussion: SUA levels were closely associated with MetS and its components, even in nonobese subjects. Therefore, high SUA levels in children and young adolescents should be closely monitored to prevent MetS.

Treatment of congenital hypogonadotropic hypogonadism in male patients.

Congenital hypogonadotropic hypogonadism (CHH) is characterized by complete or partial failure of pubertal development because of inadequate secretion of gonadotropic hormones. CHH consists of hypogonadotropic hypogonadism with anosmia or hyposmia, Kallmann syndrome, and the normosmic variation normosmic idiopathic hypogonadotropic hypogonadism. CHH is one of the few treatable diseases of male infertility, although men with primary testicular dysfunction have irreversibly diminished spermatogenic capacity. The approach to CHH treatment is determined by goals such as developing virilization or inducing fertility. This review focuses on the current knowledge of therapeutic modalities for inducing puberty and fertility in men with CHH.

Reference Ranges of Body Composition Using Dual-Energy X-Ray Absorptiometry and Its Relation to Tri-Ponderal Mass Index.

Introduction/background Increased body fat is related to obesity and its comorbidities later in life. To determine the amount of body fat in children and adolescents, reference intervals should be applied. Dual-energy X-ray absorptiometry (DXA) is a good tool for accurately measuring body composition. Methodology The body composition reference ranges in Korean children and adolescents were determined using nationally representative cross-sectional data. The performances of the body mass index (BMI) and tri-ponderal mass index (TMI) in measuring body fat were compared using the reference percentiles derived from this analysis. Results A total of 1,661 subjects (891 boys and men and 770 girls and women) were included. Age- and sex-specific percentiles and the corresponding LMS variables for DXA-assessed parameters for the whole body and the trunk were determined. The coefficients of determination of the whole body FM SDS and FMI SDS for the BMI SDS were 0.783 and 0.784, respectively, and those for the TMI SDS were 0.685 and 0.769, respectively. Conclusion Based on the reference values for body composition, the correlation coefficients of TMI for adjusted FM measured by DXA were comparable to those of BMI. TMI estimated body fat levels more accurately than BMI in this study population.

Updated reference ranges for aminotransferase levels of Korean children and young adolescents based on the risk factors for metabolic syndrome.

We investigated the reference values of liver enzymes based on cardiometabolic risks among children and adolescents using the Korea National Health and Nutrition Examination Survey. A total of 8091 subjects aged 10-18 years were included from the data from 2007-2017. Overall, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the AST/ALT ratio varied with sex and age. AST levels tended to decrease with age, but ALT levels had a U-shaped curve, which resulted in a gradual increase in the AST/ALT ratio after age 13. The prevalence of MetS was strongly associated with elevated AST or ALT and a decreased AST/ALT ratio. The prevalence ratios of the development of MetS were also elevated in groups with high levels of AST and ALT and a low AST/ALT ratio. Particularly in the combined ALT and AST/ALT analyses, borderline-high levels also showed a high prevalence ratio of MetS. Liver enzymes were also involved in the increase in the adjusted mean values for each risk factor for MetS. Here, we provided updated reference values for liver enzymes based on the analysis between population-based data and cardiometabolic risk factors; AST, ALT and the AST/ALT ratio might be useful in the early diagnosis and treatment of MetS.

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.

Metabolic risk assessment in children and adolescents using the tri-ponderal mass index.

We assessed the risk of metabolic syndrome in children and adolescents who were classified using the tri-ponderal mass index (TMI) with data from the Korea National Health and Nutrition Examination Survey (KNHANES). Data from 10 to 18-year-old subjects that were overweight or obese (n = 1362) were extracted from the KNHANES 2007-2018. Weight classifications were determined by TMI and included overweight and Class I, Class II, and Class III obesity. The standard deviation scores (SDS) of weight, waist circumference, and body mass index (BMI) as well as cardiometabolic risk factors, including blood pressure, serum glucose levels, total cholesterol (T-C), triglycerides, HDL-c, and low-density lipoprotein cholesterol (LDL-c), worsened with the severity of obesity. Most risk factors showed a linear association with the severity increase, except for fasting glucose levels, T-C, and LDL-c. The prevalence of cardiometabolic risks also increased with the severity of obesity, which developed earlier in boys than in girls. The risk of metabolic syndrome significantly increased with the severity of obesity in both unadjusted and adjusted analyses. TMI reflected the severity of obesity and predicted the risk of metabolic syndrome and its components. Therefore, clinical applications of TMI could be a useful to identify the incidence of childhood obesity and metabolic syndromes.

Aberrant Notch Signaling Pathway as a Potential Mechanism of Central Precocious Puberty.

The Notch signaling pathway is highly conserved during evolution. It has been well documented that Notch signaling regulates cell proliferation, migration, and death in the nervous, cardiac, and endocrine systems. The Notch pathway is relatively simple, but its activity is regulated by numerous complex mechanisms. Ligands bind to Notch receptors, inducing their activation and cleavage. Various post-translational processes regulate Notch signaling by affecting the synthesis, secretion, activation, and degradation of Notch pathway-related proteins. Through such post-translational regulatory processes, Notch signaling has versatile effects in many tissues, including the hypothalamus. Recently, several studies have reported that mutations in genes related to the Notch signaling pathway were found in patients with central precocious puberty (CPP). CPP is characterized by the early activation of the hypothalamus-pituitary-gonadal (HPG) axis. Although genetic factors play an important role in CPP development, few associated genetic variants have been identified. Aberrant Notch signaling may be associated with abnormal pubertal development. In this review, we discuss the current knowledge about the role of the Notch signaling pathway in puberty and consider the potential mechanisms underlying CPP.

Positive Associations between Body Mass Index and Hematological Parameters, Including RBCs, WBCs, and Platelet Counts, in Korean Children and Adolescents.

We conducted this study to investigate the associations between hematological parameters and obesity in children and adolescents. The levels of hematological parameters (including white blood cells [WBCs], red blood cells [RBCs], hemoglobin [Hb], hematocrit [Hct], and platelets) of 7997 participants (4259 boys and 3738 girls) aged 10-18 years were recorded. The parameters were compared among participants with normal weight, overweight, and obesity. Significantly higher mean levels of WBCs (7.16 vs. 6.16 × 103/mm3, p < 0.001), RBCs (4.90 vs. 4.82 × 106/mm3, p < 0.001), Hb (14.07 vs. 13.99 g/dL, p < 0.05), Hct (42.31 vs. 41.91%, p < 0.001), and platelets (311.87 vs. 282.66 × 103/mm3, p < 0.001) were found in the obese than normal weight group, respectively, after adjusting for body mass index (BMI) and sex. BMI SDS had significant positive associations with the levels of WBCs (ß = 0.275, p < 0.001), RBCs (ß = 0.028, p < 0.001), Hb (ß = 0.034, p < 0.001), Hct (ß = 0.152, p < 0.001), and platelets (ß = 8.372, p < 0.001) after adjusting for age, sex, and socioeconomic factors in a multiple linear regression analysis. A higher BMI was associated with elevated WBC, RBC, Hb, Hct, and platelet counts in children and adolescents. Because higher levels of hematological parameters are potential risk factors for obesity-related diseases, hematological parameters should be evaluated in obese children and adolescents.

Comparison of the clinical characteristics and outcomes of pediatric patients with and without diabetic ketoacidosis at the time of type 1 diabetes diagnosis.

PURPOSE: We investigated the possible effects of diabetic ketoacidosis (DKA) at the initial diagnosis of type 1 diabetes mellitus (T1DM) on the clinical outcomes of pediatric patients. METHODS: Medical records of children and adolescents with newly diagnosed T1DM seen in the Ajou University Hospital from January 2008 to August 2020 were reviewed and analyzed. RESULTS: Among 129 diagnosed T1DM patients, 40.3% presented with DKA. Although demographic and basic characteristics did not differ between DKA and non-DKA patients, DKA patients needed a significantly higher insulin dosage than non-DKA patients for 2 years after diagnosis. However, control of glycated hemoglobin was not different between the DKA and non-DKA groups during the observation period. In the biochemical analysis, C-peptide, insulin-like growth factor-1, and insulin-like growth factor binding protein 3, high-density lipoprotein cholesterol, free T4, and T3 values were lower, but thyroid-stimulating hormone, initial serum glucose, uric acid, total cholesterol, triglyceride, and low-density lipoprotein cholesterol values were higher in DKA patients than non-DKA patients at the diagnosis of T1DM; however, these differences were temporarily present and disappeared with insulin treatment. Other clinical outcomes, such as height, thyroid function, and urine microalbumin level, did not vary significantly between the DKA and non-DKA groups during 5 years of follow-up. CONCLUSION: DKA at initial presentation reflects the severity of disease progression, and the deleterious effects of DKA seem to impact insulin secretion. Although no difference in long-term prognosis was found, early detection of T1DM should help to reduce DKA-related islet damage and the socioeconomic burden of T1DM.

Silodosin for Prevention of Ureteral Injuries Resulting from Insertion of a Ureteral Access Sheath: A Randomized Controlled Trial.

BACKGROUND: The ureteral access sheath (UAS) is an ancillary device widely used by urologists, but acute ureter injury may occur following its insertion. Preoperative selective oral α1-blockers can reduce intraureteral pressure, and prevent ureteral wall injury during UAS insertion. OBJECTIVE: To compare perioperative data of patients who underwent flexible ureterorenoscopy (fURS) with UAS with and without premedication with silodosin. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 100 patients from a single institution who underwent retrograde intrarenal surgery for kidney and upper ureter stone removal were prospectively allocated from May 2018 to March 2019. INTERVENTION: The experimental groups received silodosin for 3 d preoperatively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint included ureteral injuries after UAS insertion that were assessed according to endoscopic classification. The secondary endpoint was an evaluation of whether premedication with silodosin had any effect on postoperative outcomes. RESULTS AND LIMITATIONS: A total of 44 and 43 patients were randomly assigned to the control and experimental groups, respectively. Silodosin prevented significant postoperative ureteral injury involving the smooth muscle layer more successfully than in the control group (9.3% vs 27.3%; p = 0.031). There was no significant difference in the overall complication rate as determined by the modified Clavien-Dindo classification system and the computed tomography scan stone-free rate postoperatively. Patients who received silodosin before fURS reported lower pain scores than those in the control group using a visual analog scale (p = 0.009). Limitation included a lack of placebo comparison. CONCLUSIONS: Our data suggest that preoperative silodosin protects against significant ureteral injury related to UAS insertion during fURS and decreases postoperative pain level. Silodosin premedication might be an effective and safe technique to replace prestenting. PATIENT SUMMARY: We investigated the preventive effect of an α-blocker against perioperative complication caused by ureteral access sheath inserted during flexible ureterorenoscopy. Taking silodosin before surgery prevented ureter wall injury during surgery and immediately improved postoperative pain.

Genetic factors in precocious puberty.

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and noncoding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.

Biochemical predictors of metabolically unhealthy obesity in children and adolescents.

BACKGROUND: Children and adolescents with obesity can now be classified according to metabolic profile, as those with metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUO). We aimed to determine the prevalence of MUO and identify its biochemical predictors in pediatric patients with obesity. METHODS: We evaluated the medical records of 187 boys and girls with obesity. The children were divided into MHO and MUO groups, and anthropometric and biochemical parameters were assessed. Oral glucose tolerance test (OGTT) was used to identify impaired glucose regulation and hyperinsulinism, and binary logistic regression analysis was used to determine predictors of MUO in children with obesity. RESULTS: Of the 187 children, MUO was found in 71.7% (n=134) and MHO in 28.3% (n=53); those in the MHO group were younger than those in the MUO group. Blood pressure, triglyceride, total cholesterol, and uric acid levels were significantly higher in the MUO group than in the MHO group. Further, the MUO group exhibited a significantly higher level of insulin resistance (p<0.05) than the MHO group. Serum levels of uric acid and homeostasis model assessment of insulin resistance index (HOMA-IR) were confirmed as biochemical predictors of the MUO phenotype in children with obesity. CONCLUSIONS: The ratio of MUO in children with obesity was relatively high; further, serum levels of uric acid and HOMA-IR can be used as biochemical predictors of MUO.

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.