Obesity is becoming the most frequently diagnosed chronic disease in many countries affecting all age groups and specifically the pediatric population. To date, most approaches have focused on changing the behavior of individuals with respect to diet and exercise. Almost all researchers agree that prevention could be the key strategy for controlling the current epidemic of obesity. Prevention may be achieved by changes in lifestyle through a variety of interventions targeting the urban environment, physical activity, time spent watching television and playing computer games and consumption of carbonated drinks. However, as yet, these strategies seem to have had little impact on the growing increase of the obesity epidemic. In this article, we aimed to discuss the effect of rapid urbanization on childhood obesity and to suggest solutions to this problem.

Objective: It is important to identify the possible risk factors for the occurrence of large for gestational age (LGA) in newborns and to determine the effect of birth weight and metabolic parameters on subsequent growth. We aimed to determine the effects of maternal weight, weight gain during pregnancy, maternal hemoglobin A1c (HbA1c), C-peptide and insulin as well as cord C-peptide and insulin levels on birth weight and postnatal growth during the first two years of life.
Methods: Healthy, non-diabetic mothers and term singleton newborns were included in this prospective case-control cohort study. Fasting maternal glucose, HbA1c, C-peptide and insulin levels were studied. Cord blood was analyzed for C-peptide and insulin. At birth, newborns were divided into two groups according to birth size: LGA and appropriate for GA (AGA). Infants were followed at six-month intervals for two years and their length and weight were recorded.
Results: Forty LGA and 43 AGA infants were included in the study. Birth weight standard deviation score (SDS) was positively correlated with maternal body mass index (BMI) before delivery (r=0.2, p=0.04) and with weight gain during pregnancy (r=0.2, p=0.04). In multivariate analyses, the strongest association with macrosomia was a maternal C-peptide level >3.85 ng/mL (OR=20). Although the LGA group showed decreased growth by the 6-month of follow-up, the differences between the LGA and AGA groups in weight and length SDS persisted over the 2 years of follow-up.
Conclusion: The control of maternal BMI and prevention of overt weight gain during pregnancy may prevent excessive birth weight. The effect of the in utero metabolic environment on the weight and length SDS of infants born LGA persists until at least two years of age.

Objective: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines.
Methods: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension.
Results: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, p<0.05). RANTES was significantly higher in the pre-treatment hypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (p<0.05).
Conclusion: Th1 cells could be activated in obese hypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension.

Objective: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS.
Methods: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated.
Results: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others.
Conclusion: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients.

Objective: Kisspeptin levels have been reported in children with premature thelarche, precocious puberty and adolescent gynecomastia, but there are no reports on kisspeptin levels in the neonatal period. This study aimed to investigate plasma kisspeptin hormone levels in newborns with and without breast enlargement.
Methods: Plasma kisspeptin levels and other related biochemical variables were investigated in this prospective study conducted on 40 (20 girls and 20 boys) newborn infants with breast enlargement and on 40 healthy control infants (20 girls and 20 boys). Two-milliliter venous blood samples were taken in hemogram tubes with K2EDTA. Kisspeptin assays were performed using the enzyme-immunoassay method.
Results: Mean plasma kisspeptin levels were 0.6±0.2 ng/mL in the study group and 0.5±0.2 ng/mL in the control group. Plasma kisspeptin concentrations were significantly higher in the study group (p=0.039) and also showed a correlation with serum prolactin levels (p=0.006). Significant correlations were also determined between plasma kisspeptin and luteinizing hormone concentrations (p=0.05, r=0.312).
Conclusion: The findings of this study suggest that plasma kisspeptin and serum prolactin levels may be involved in the physiopathology of breast enlargement in newborns.

Objective: Malnutrition continues to be a leading cause of stunted growth in many countries. This study aimed to investigate serum nesfatin-1 and orexin-A levels in underweight children and the potential correlations of these levels with anthropometric and nutritional parameters.
Methods: The study enrolled 44 prepubertal children (between 2 and 12 years of age) with thinness grades of 1-3 and 41 healthy age- and gender-matched children. The demographic, clinical and laboratory parameters including nesfatin-1 and orexin-A concentrations were compared between the two groups. The correlations of nesfatin-1 and orexin-A with biochemical and anthropometric parameters were investigated. The receiver operating characteristic (ROC) analysis were also performed for evaluating nesfatin-1 and orexin-A in distinguishing children with malnutrition from healthy controls.
Results: Thyroid-stimulating hormone, vitamin B12 and insulin levels were significantly lower in the study group than controls (p=0.001, p=0.049 and p=0.033, respectively). Mean nesfatin-1 levels in the malnourished group was also significantly lower compared to the healthy controls (3871.2±1608.8 vs. 5515.0±3816.4 pg/mL, p=0.012). No significant difference was observed in the orexin-A levels between the two groups (malnourished vs. control groups: 1135.7±306.0 vs. 1025.7±361.6 pg/mL, p=0.141). Correlation analyses revealed a positive correlation of nesfatin-1 and a negative correlation of orexin-A with body mass index (BMI) z-score. ROC analysis demonstrated that nesfatin-1 and orexin-A cannot be used to distinguish children with malnutrition from healthy controls (AUC: 0.620, p=0.061 for nesfatin-1 and AUC: 0.584, p=0.190 for orexin-A).
Conclusion: The positive correlation of nesfatin-1 and the negative correlation of orexin-A with BMI suggest that these neuropeptides may be a part of a protective mechanism in the maintenance of nutritional status and that they may have a role in regulating food intake in undernourished children.

Objective: To evaluate the effects of diabetic ketoacidosis (DKA) on neurocognitive functions in children and adolescents presenting with new-onset type 1 diabetes.
Methods: Newly diagnosed patients were divided into two groups: those with DKA and those without DKA (non-DKA). Following metabolic stabilization, the patients took a mini-mental status exam prior to undergoing a baseline battery of cognitive tests that evaluated visual and verbal cognitive tasks. Follow-up testing was performed 8-12 weeks after diagnosis. Patients completed an IQ test at follow-up.
Results: There was no statistical difference between the DKA and non-DKA groups neither in alertness at baseline testing nor in an IQ test at followup. The DKA group had significantly lower baseline scores than the non-DKA group for the visual cognitive tasks of design recognition, design memory and the composite visual memory index (VMI). At follow-up, Design Recognition remained statistically lower in the DKA group, but the design memory and the VMI tasks returned to statistical parity between the two groups. No significant differences were found in verbal cognitive tasks at baseline or follow-up between the two groups. Direct correlations were present for the admission CO2 and the visual cognitive tasks of VMI, design memory and design recognition. Direct correlations were also present for admission pH and VMI, design memory and picture memory.
Conclusion: Pediatric patients presenting with newly diagnosed type 1 diabetes and severe but uncomplicated DKA showed a definite trend for lower cognitive functioning when compared to the age-matched patients without DKA.

Objective: Hyperthyrotropinemia, which can be either a permanent or a transient state, is an asymptomatic condition and there is a controversy in management and long-term consequences. The aim of this study was to evaluate the results of thyrotropin-releasing hormone (TRH) test in infants with hyperthyrotropinemia.
Methods: Data of the patients who underwent a TRH test for mildly elevated thyroid-stimulating hormone (TSH) levels between 2004 and 2011 in a single academic pediatric endocrinology unit were retrospectively reviewed from the case files.
Results: Twenty infants (13 female, 7 male) with the median (range) age of 33 days (25-50) were enrolled into the study. The median basal TSH was 7.0 mIU/L (4.9-8.9) and free thyroxine level was 1.4 ng/mL (1.2-1.6) at the time of the TRH test. Thyroid ultrasonography was performed to 10 of the cases, and one of them had thyroid hypoplasia. TRH test revealed normal results in four infants, while sixteen infants had exaggerated response suggestive of primary hypothyroidism. The median follow-up period was 3.5 years (2.3-3.7). Therapy was discontinued in seven cases (2 had normal TRH response, 5 had exaggerated response) with the median age of 3.2 years (2.5-4). Of these seven infants, three had an elevated TSH on follow-up and L-thyroxine was restarted. All of the infants, in whom therapy was restarted, had exaggerated response to TRH.
Conclusion: TRH test response could be a useful diagnostic test to evaluate the persistence of the disease during the infantile age period.

Objective: Cardiovascular, respiratory and musculoskeletal system disorders which may affect the functional exercise capacity are common in obese patients. We aimed to investigate the functional exercise capacity and its relationship with functional pulmonary capacity in obese children.
Methods: A total of 74 obese and 36 healthy children as a control group were enrolled in the study. Pulmonary functions and functional exercise capacity were measured by spirometry and six-minute walk test (6 MWT), respectively.
Results: The distances covered during the 6 MWT in obese and control groups were 570.9±67.5 and 607.8±72.5 meters, respectively (p=0.010). In spirometric pulmonary function tests (PFTs), forced expiratory volume in 1 sec (FEV1) and forced mid-expiratory flows (25-75) were lower in the obese group (p=0.048 and p=0.047, respectively), whereas forced vital capacity (FVC), the FEV1/FVC ratio and peak expiratory flow were not statistically different between the obese and control groups. Multiple regression analysis revealed that among all parameters of anthropometric measures and PFTs, only body mass index standard deviation score (BMI-SDS) was the independent factor influencing 6 MWT.
Conclusion: Functional exercise and lung capacities of obese children were diminished as compared to those of non-obese children. The most important factor influencing functional exercise capacity was BMI-SDS.

Objective: The aim of this study was to evaluate the periaortic fat thickness (PAFT) using conventional echocardiography in obese children and adolescents with non-alcoholic fatty liver disease (NAFLD).
Methods: Two hundred and ninety-seven obese children and adolescents were included in the study. Anthropometric measurements were made in all subjects, and fasting venous blood samples were taken for determination of glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Ultrasonography of the liver was used for assessment of NAFLD and the subjects were grouped as NAFLD and non-NAFLD. Echocardiography was performed in all subjects.
Results: PAFT was higher in patients with NAFLD compared with the non-NAFLD group. In patients with NAFLD, PAFT was positively correlated with waist circumference and with total cholesterol levels. In multiple regression analysis, waist circumference (ß=0.28, p=<0.001) was found to be the best predictor of PAFT.
Conclusion: Conventional echocardiography may be used to determine increased PAFT at an early stage in obese children and adolescents with NAFLD for careful monitoring of cardiovascular risk.

Objective: Childhood-onset obesity is associated with increased mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. Dyslipidemia has a fundamental role in the pathogenesis of CVD. This study aimed to evaluate the prevalence of dyslipidemia and related factors among obese children and adolescents.
Methods: Obese patients aged between 2 and 18 years were included in the study. Serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), fasting glucose levels, insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver ultrasound findings were evaluated retrospectively.
Results: Among 823 obese patients, 353 (42.9%) met the dyslipidemia criteria: 21.7% had hypertriglyceridemia, 19.7% had low levels of HDL-C, 18.6% had hypercholesterolemia, and 13.7% had high levels of LDL-C. Older age and/or high body mass index (BMI) were related to increased prevalence of dyslipidemia. Hepatosteatosis was more common among dyslipidemic patients. The frequency of insulin resistance (IR) and of higher levels of ALT and TSH were also detected in dyslipidemic patients. Patients with both dyslipidemia and grade 2-3 hepatosteatosis had higher levels of ALT, AST and TSH and lower levels of fT4.
Conclusion: Prevalence of dyslipidemia is high in obese children, and hypertriglyceridemia is in the foreground. Higher levels of IR and more apparent abnormal liver function test results are observed in the context of dyslipidemia and hepatosteatosis coexistence. Metabolic and hormonal alterations related with thyroid functions may also be associated with dyslipidemia and hepatosteatosis in obese patients.

Growth and pubertal development are important health markers. We used the data of a longitudinal growth study on a contemporary sample of US youth to examine the relationship between peak height velocity (PHV) and Tanner staging. We observed a substantial variability in the timing of PHV across Tanner stages, which is an important consideration for clinicians when assessing growth.

Congenital hypothyroidism (CH) occurs with a prevalence of approximately 1:4000 live births. Defects of thyroid hormone synthesis account for 15-20% of these cases. Thyroid peroxidase (TPO) gene is the most common cause for dyshormonogenesis. So far, more than 60 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. We present an 8-day-old male with mild CH who was identified to have a G to A transition in the fifth codon of the TPO gene (c.13G>A; p.Ala5Thr). The unaffected family members were heterozygous carriers of the mutation, whereas 400 healthy individuals of the same ethnic background did not have the mutation. Mutation analysis of 11 known causative CH genes and 4 of our own strong candidate genes with next-generation sequencing revealed no mutations in the patient nor in any other family members. The results of in silico functional analyses indicated partial loss-of-function (LOF) in the resulting enzyme molecule due to mutation. The patient’s clinical finding s were consistent with the effect of this partial LOF of the mutation. In conclusion, we strongly believe that A5T alteration in the TPO gene is actually pathogenic and suggest that it should be classified as a mutation.

Testotoxicosis is a rare disorder which presents as isosexual peripheral precocious puberty in males. Despite the pattern of autosomal dominant inheritance, sporadic cases also may occur. Due to activating mutation in luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene, early virilization and advancement in bone age are common with increased serum testosterone levels above adult ranges, despite low LH and follicular-stimulating hormone (FSH) levels. There are different treatment regimens, such as combination of bicalutamide (antiandrogen agent) and a third-generation aromatase inhibitor, that are reported to be well-tolerated and successful in slowing bone age advancement and preventing progression of virilization. We report here two patients who presented with peripheral precocious puberty and an activating mutation in the LHCGR gene: one with a family history and previously determined mutation and the other without family history and with a novel mutation (c.830G>T). Combination of bicalutamide+anastrozole was ineffective in slowing pubertal progression and bone age. Short-term results were better with ketoconazole.

17-ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is an important enzyme involved in the final steps of androgen synthesis and is required for the development of normal male external genitalia. 46,XY individuals with deficiency of this enzyme present a wide clinical spectrum from a female appearance of the external genitalia through ambiguous genitalia to a predominantly male genitalia with micropenis or hypospadias. This paper reports a one-year-old 46,XY patient with 17ß-HSD3 deficiency who presented with female external genitalia and bilaterally palpable gonads in the inguinal region. The low T/?4 ratio after human chorionic gonadotropin (hCG) stimulation suggested 17ß-HSD3 deficiency. A homozygous mutation, c.761_762delAG, was determined at the intron 9/exon 10 splice site of the HSD17B3 gene. To the best of our knowledge, this mutation has not been reported thus far, but its localization and type would imply a complete disruption of the 17ß-HSD3 which may explain the phenotype of our patient.