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.

Healthcare professionals' perspectives towards the digitalisation of paediatric growth hormone therapies: expert panels in Italy and Korea.

Introduction: To analyse the perspectives of healthcare professionals (HCPs) regarding the acceptance of digital health solutions for growth hormone (GH) deficiency care. This study identified factors impacting HCPs' intent to use and recommend digital solutions supporting recombinant-human growth hormone (r-hGH) therapy in Italy and Korea with a use case of connected drug delivery system (Aluetta® with Smartdot™) integrated in a platform for GH treatment support (the Growzen™ digital health ecosystem). Methods: Participatory workshops were conducted in Rome, Italy, and Seoul, Korea, to collect the perspectives of 22 HCPs on various predefined topics. HCPs were divided into two teams, each moderated by a facilitator. The workshops progressed in five phases: introduction of the project and experts, capturing views on the current context of digitalisation, perceived usefulness and ease of use of Aluetta® with Smartdot™, exploration of the perception of health technology evolution, and combined team recommendations. Data shared by HCPs on technology acceptance were independently analysed using thematic analysis, and relevant findings were shared and validated with experts. Results: HCPs from both Italy and Korea perceived Aluetta® with Smartdot™ and the Growzen™ based digital health ecosystem as user-friendly, intuitive, and easy-to-use solutions. These solutions can result in increased adherence, a cost-effective healthcare system, and medication self-management. Although technology adoption and readiness may vary across countries, it was agreed that using digital solutions tailored to the needs of users may help in data-driven clinical decisions and strengthen HCP-patient relationships. Conclusion: HCPs' perspectives on the digitalisation in paediatric GH therapies suggested that digital solutions enable automatic, real-time injection data transmission to support adherence monitoring and evidence-based therapy, strengthen HCP-patient relationships, and empower patients throughout the GH treatment process.

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.

Case report describing a patient with diazoxide resistant congenital hyperinsulinism resulting from compound heterozygous mutations in the ABCC8 gene.

Congenital hyperinsulinism (CHI) is an over-secretion of insulin by pancreatic ß-cells, causing hypoglycemia which can inhibit brain development in infants. CHI is primarily associated with mutations in the ABCC8 or KCNJ11 genes, which encode the SUR1 and KIR 6.2 subunits of the ATP-sensitive potassium (KATP) channel. Here, we report a case of hyperinsulinemic hypoglycemia with ABCC8 gene mutation in a full term, female, Korean infant who developed early onset hypoglycemia but was not subject to either genetic or metabolic workup. This infant was later admitted to the ER because of a hypoglycemic seizure, but her metabolic work up revealed that both her fasting insulin and C-peptide levels were within the normal range. Despite this glucagon stimulation produced positive results and the genetic workup revealed c.[298G>T(;)4252C>T] mutations in the ABCC8 gene. This indicated diazoxide treatment, but following an unsuccessful course of treatment we switched to octreotide which helped stabilize her glucose. Over 5 years of follow-up, the patient treated with a low dose of octreotide has had no hypoglycemic event, and her growth and psychomotor development remained within normal ranges. However, she is severely obese (BMI over 97 %) despite using octreotide. Thus, we report a mild case of CHI with octreotide treatment, wherein the patient has normal insulin and C-peptide levels and normal development, but is severe obese.

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.

Long-term effectiveness of growth hormone therapy in children born small for gestational age: An analysis of LG growth study data.

PURPOSE: Growth hormone (GH) treatment has been used to improve growth in short children who were born small for gestational age (SGA). The aim of this study was to investigate the long-term efficacy of GH treatment in these children. METHODS: Data from a multicenter observational clinical trial (ClinicalTrials.gov NCT01604395, LG growth study) were analyzed for growth outcome and prediction model in response to GH treatment. One hundred fifty-two children born SGA were included. RESULTS: The mean age of patients born SGA was 7.13 ± 2.59 years. Height standard deviation score (SDS) in patients born SGA increased from -2.55 ± 0.49 before starting treatment to -1.13 ± 0.76 after 3 years of GH treatment. Of the 152 patients with SGA, 48 who remained prepubertal during treatment used model development. The equation describing the predicted height velocity during 1st year of GH treatment is as follows: the predictive height velocity (cm) = 10.95 + [1.12 x Height SDS at initial treatment (score)] + [0.03 x GH dose (ug/kg/day)] + [0.30 x TH SDS at initial treatment (score)] + [0.05 x age (year)] + [0.15 x Weight SDS at initial treatment (score)] ± 1.51 cm. CONCLUSIONS: GH treatment improved growth outcome in short children born SGA. We also developed a prediction model that is potentially useful in determining the optimal growth outcome for each child born SGA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01604395.

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.

Hyperosmolar hyperglycemic state as the first manifestation of type 1 diabetes mellitus in an adolescent male: a case report.

A hyperosmolar hyperglycemic state (HHS) is a life-threatening complication rarely seen in children and adolescents with type 1 diabetes mellitus (T1DM). However, early diagnosis and proper treatment are vital to reduce the high morbidity and mortality rates associated with HHS. We describe a male patient who presented with polydipsia, polyuria, and a drowsy mental status. His initial biochemistry results demonstrated severe hyperglycemia (1,456 mg/dL), hyperosmolarity of 359 mOsm/kg (effective osmolarity, 323 mOsm/kg), and mild acidosis (venous pH, 7.327). The patient was diagnosed with HHS and T1DM based on the presence of hyperosmolarity, hyperglycemia, and positivity for antiglutamic acid antibodies. Intensive intravenous fluid and regular insulin (0.025 units/kg/hr) were administered. After hydration and insulin treatment, the patient's mental status and serum glucose and sodium levels improved, and no neurological complications were observed. In summary, most cases of HHS are observed in adult patients with type 2 diabetes. However, occurrences in children and adolescents with T1DM have also been reported. Therefore, HHS should be considered in the differential diagnosis of hyperglycemic emergencies.