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With this review, we aim to focus the attention on some established as well as new concepts for the metabolic syndrome (MetS) in children and adolescents spanning from definition to recommendations for the diagnostic approach. Even though there is no international commonly used definition of the metabolic syndrome in children and adolescents, all definitions include obesity as precondition for the development of MetS even in children. Obesity is one of the major cardiometabolic risk factors and it is strongly linked to other metabolic diseases like hyperlipidemia, hyperinsulinemia as well as hypertension. The metabolic syndrome is commonly known as a constellation of the mentioned morbidities. Pediatricians and researchers agree that early diagnosis and early interventions of the MetS are important to improve the prevention of cardiovascular disease and type 2 diabetes in adulthood. However, this requires appropriate screening tools for children and adolescents at risk for the MetS and its comorbidities. Due to controversies regarding the definition of MetS and the lack of consensus thresholds for the single components in children and adolescents, there is no internationally accepted diagnostic pathway for MetS available. However, several consensus statements and national guidelines for the assessment of obesity and its comorbidities in children and adolescents are available. Obesity seems to be the driving factor for the development of the other risk factors of MetS. In order to avoid conflicts concerning the definition of overweight and obesity, we recommend using the WHO definition of overweight (one standard deviation body mass index for age and sex and obesity; two standard deviations body mass index for age and sex) in children and adolescents.

Objectives Metabolic syndrome (MS) is a fatal endocrinopathy that begins with insulin resistance (IR) and causes abdominal obesity, glucose intolerance, or systemic disorders. This study was aimed to determine the cut-off values for the triglyceride (TG)/high-density lipoprotein cholesterol (TG/HDL-C) ratio, the TG glucose (TyG) index and homeostasis model assessment (HOMA-IR) for the diagnosis of MS in obese adolescents, and to compare which of the three indexes would offer a more accurate approach to diagnosis. Methods The study population comprised 1,171 obese adolescents (639 females and 532 males aged 10-16 years, Body Mass Index (BMI)>=95th percentile). Indirect measures of IR screening for MS were the TG/HDL ratio, TyG index, and HOMA-IR. The cut-off values of the TG/HDL ratio, TyG index, and HOMA-IR were obtained from receiver operation characteristic (ROC) curves. Results HOMA-IR had a significant positive correlation with the TyG index (r=0.352, p<0.001) and TG/HDL-C (r=0.291, p<.001). The TyG index and TG/HDL-C showed a strong positive correlation (r=0.901, p<0.001). The TG/HDL-C ratio showed a larger ROC Area under Curve (AUC=0.849) than HOMA-IR index (AUC=0.689), but as a predictor similar to TyG index (AUC=0.833) when screening for MS. The cut-off values for MS were as follows: TG/HDL-C ratio>2.16 (sensitivity: 88.8%; specificity: 49.7%), TyG index>8.50 (sensitivity: 85.6%; specificity: 57.0%) and HOMA-IR>2.52 (sensitivity: 83.2%; specificity: 40.4%). Conclusions Both the TyG index and TG/HDL-C ratio are better markers than HOMA-IR to determine the risk of metabolic syndrome according to IDF criteria. Besides, the TyG index and TG/HDL-C ratio have similar differentiating powers to determine this risk in obese Turkish adolescents.

Background: Bone metabolism involves many complex pathways that are disturbed by several bone diseases. The literature shows some limitations concerning pediatric reference intervals to bone markers, mainly because of the low number of patients included in the studies, the heterogeneity of methods, beyond the fact that it is time-consuming and expensive. The aim of this study was to determine reference values for β-isomerized carboxy-terminal telopeptides collagen type I (β-CTX), a marker of bone resorption, for children and adolescents., Methods: Blood samples from 246 patients were collected and β-CTX was measured using an electrochemiluminescence immunoassay (ECLI)., Results and Conclusions: We propose reference ranges for β-CTX concentration from the 2.5 percentile and 97.5 percentile for each age group. The reference values obtained, concerning children and adolescents, might be useful in the evaluation of diseases such as osteosarcoma and anorexia in both childhood as adolescence.

Background: Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test., Objective: To determine the best predictive model for detecting puberty in girls., Subjects: Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15)., Methods: Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed., Results: The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%., Conclusions: The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.

Aim: To assess the reliability of pubertal self-assessment of Thai adolescents., Subjects: Some 927 girls and 997 boys, aged 8-18 years, from nine schools in Hat-Yai municipality., Methods: The adolescents evaluated their pubertal status after being shown a line drawing of the five Tanner stages with a short description. Girls assessed their breast and pubic hair development, and boys assessed their pubic hair development. The pubertal self-assessments were compared to pubertal assessments made by a pediatrician who examined the children after their self-assessment. Kappa coefficient and percent agreement were used for statistical analysis., Results: The percent agreement of breast and pubic hair development between the girl's self-assessments and the assessments by the pediatrician were 60.8% and 78%, respectively. Kappa coefficient for breast assessment was 0.50 (95% confidence interval, CI 0.47-0.53) and for pubic hair 0.68 (95% CI 0.65-0.72). Nearly 30% of girls aged younger than 10 years overestimated their breast development status while 45% of girls aged over 14 years underestimated their breast development (p<0.001). For boys, the percent agreement of pubic hair development between the adolescents and the pediatrician was 76.4%, with a weighted kappa coefficient of 0.68 (95% CI 0.65-0.72)., Conclusion: Pubertal self-assessment using line drawings with a short description can be used as a reliable method to assess pubic hair maturation in boys and girls, but can be used with less reliability to assess the breast maturation in young girls.

Here we report the case of a young girl who had vague signs and symptoms potentially attributable to hyperthyroidism and was found to have autoimmune thyroiditis and hyperthyroxinemia. The elevated serum free thyroxine levels were persistent when measured by both standard assays and equilibrium dialysis/high-pressure liquid chromatography-tandem mass spectrometry. The clinical symptoms, with discordant thyroid test results, created a diagnostic dilemma that led initially to unnecessary additional evaluations. She was ultimately found to have familial dysalbuminemic hyperthyroxinemia (FDH) and required no therapy. This case highlights the inherent difficulties in evaluating children, who typically have vague signs and symptoms of thyroid dysfunction, when, in addition, they have an unrelated acquired (autoimmune) as well as a genetic (FDH) defect. The benefit of including testing for immediate members of the family is emphasized.

The objective was to determine the probability of receiving steroid treatment following an insulin tolerance test (ITT) for short-stature evaluation and to evaluate the utility of a subsequent cortrosyn stimulation test (CST) in determining adrenal sufficiency. We retrospectively analyzed the hypothalamic-pituitary-adrenal (HPA) axis evaluation in short-stature subjects during the 5-year period from January 2005 to December 2009. The probability of receiving steroid treatment was < 10% when the maximum cortisol concentration during an ITT was < 8.4 microg/dL. In the event of a suboptimal cortisol response during an ITT, only a single 1-microg CST is recommended for assessment of adrenal function.

Priming with sex steroids in stimulation tests for the diagnosis of GHD is still under debate. Most of the data on utility of priming during GH stimulation so far seem to support its use in the diagnosis of GHD in childhood. There is a propensity to treat growth retarded children who test subnormally to stimulation tests with GH. However, some studies analyzing the final height or height gain during GH treatment in such children failed to show any improvement in height. This paper summarizes previous studies on priming to analyze the utility of priming as a valid method to better the diagnostic capacity of the test.

The insulin tolerance test (ITT) is a standard growth hormone (GH) provocative test to distinguish children with normal variant short stature (NVSS) from those with GH deficiency (GHD). We reviewed ITTs retrospectively in 52 short children using peak GH concentration of 7 ng/ ml as a cut-off level for GHD (peak GH <7 ng/ ml) and NVSS (peak GH > or =7 ng/ml). The average insulin dosage was 0.1 U/kg in children with NVSS and 0.08 U/kg in GHD. Hypoglycemia was achieved in all cases with an average plasma glucose nadir of 1.8 mmol/l (32 mg/dl) occurring between 15 and 45 min following administration. The average peak GH concentration was 12 ng/ml, occurring at 30-90 min. There were no serious adverse effects from the ITT. We conclude that the appropriate duration of ITT should be 90 minutes. The appropriate timing to obtain samples for plasma glucose level is at 0, 15, 30, 45, 60, and 90 min, and for GH concentrations at 0, 30, 45, 60, and 90 min. The shortened duration of ITT to 90 min will reduce the time spent and also the financial cost for unnecessary samples, while still ensuring a correct diagnosis for the patients.