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Objective: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) treatment in obese children with nonalcoholic fatty liver disease (NAFLD). Methods: One hundred and eight obese (body mass index (BMI) >95th percentile for age and sex) adolescents with NAFLD were included in the study. Mean age of the subjects was 13.8±3.9 years (9-17 yrs). The diagnosis of NAFLD was based on the presence of liver steatosis with high transaminases. The subjects were randomly divided into two groups. Group 1 (PUFA group, n=52) received a 1000 mg dose of PUFA once daily for 12 months and lifestyle intervention. Group 2 (placebo group, n=56) received a recommended diet plus placebo and lifestyle intervention for 12 months. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) from fasting samples. Results: BMI, fasting insulin levels and HOMA-IR values in both groups decreased significantly at the end of the study. In group 1, 67.8% of the patients had a decrease from baseline in the prevalence of steatosis (p0.05). Conclusion: Our results indicated that n-3 PUFA treatment is safe and efficacious in obese children with NAFLD and can improve ultrasonographic findings and the elevated transaminase levels.

Objective: The aim of this study was to evaluate the effects of using ACE inhibitors on insulin resistance, glucose metabolism, body fat composition, and lipid profile in children over 10 years of age with obesity-associated metabolic syndrome (MS). Methods: A total of 53 children with MS, who had been followed for at least one year were included in the study. The sample was divided into two groups: Group 1-30 obese children (13 female, 17 male) who were not using an ACE inhibitor and Group 2-23 obese children (13 female, 10 male) who were using an ACE inhibitor. Anthropometric and laboratory dataobtained at baseline and at the 3rd, 6th, and 12th months of follow-up were compared in the two groups. Results: Comparison of the data in the two groups at 3rd, 6th, and 12th months revealed no statistically significant differences in terms of weight standard deviation score (SDS), body mass index SDS, weight for height percentile, body fat percentage, and very low-density lipoprotein (VLDL)values. However, there were statistically significant differences in mean glucose and insulin levels, homeostasis model assessment for insulin resistance, LDL and high-density lipoprotein values, and highly significant differences in mean triglyceride values. Conclusions: The positive effects of ACE inhibitor drugs, particularly on hypertriglyceridemia and insulin resistance, might bring them forth as first-line drugs in the treatment of obese and hypertensive children. Randomized, controlled, double-blind, and long-term studies are needed for a definitive conclusion. Conflict of interest:None declared.

Objective: Epicardial adipose tissue thickness (EATT) is suggested as a new cardiometabolic risk factor. Carotid intima-media thickness (IMT) is a potential indicator of subclinical atherosclerosis in patients with metabolic syndrome (MS). We investigated the association of EATT with carotid IMT and cardiac functional changes in obese adolescents with MS. Methods: One hundred thirty-eight obese adolescents and 63 lean subjects were enrolled in the study. The obese subjects were divided into two subgroups based on the presence or absence of MS (MS group and non-MS group). All subjects underwent transthoracic echocardiographic examination for determination of left ventricular (LV) function, LV mass index (LVMI), and myocardial performance index (MPI). EATT and carotid IMT were also measured during echocardiography. Results: The average LVMI measurements were higher in both MS and non-MS obese patients in comparison with the lean children. The MS group had significantly higher LVMI measurements than the non-MS and lean groups (88.5±23.0, 67.5±24.8 g/m2, and 62.4±18.2 g/m2, respectively; p

Mutations in PROP1 are the most frequent defect detected in patients with combined pituitary hormone deficiency (MIM #262600), characterized by a clinical phenotype of proportionate growth deficit due to impaired production of growth hormone in combination with deficiency of one or more of the additional anterior pituitary hormones. Approximately one third of patients with PROP1 inactivating mutations present with abnormal development of the anterior lobe of the pituitary gland as revealed by MRI. We report on the clinical and molecular characterization of the fourth complete PROP1 deletion in a girl with proportional short stature, combined pituitary hormone deficiency and a suprasellar mass mimicking a hypothalamic glioma. The proband, born to consanguineous parents, presented with proportional growth failure (height 108.8 cm, -3.48 SDS), combined pituitary hormone deficiency (GH, TSH, PRL and gonadotropins) and a suprasellar mass with optic chiasm invasion, compatible with a diagnosis of chiasmatic hypothalamic glioma, as revealed by MRI. PROP1 mutation screening by PCR and MLPA detected a homozygous deletion of the entire PROP1. The deletion was delimited to at least 7.7 kb upstream of PROP1 and more finely to ∼541-74 bp downstream from PROP1 by aCGH and PCR mapping. We describe the fourth case with a complete PROP1 deletion in homozygosis. The apparent location of the respective 5' (within a highly repetitive region, rich in Alu sequences) and 3' (within an Alu sequence) breakpoints, suggests that the deletion may have arisen through homologous recombination. The differentiation between PROP1 mutation associated pituitary enlargements from craniopharyngioma, pituitary adenoma, dys-germinoma, or Rathke's pouch cyst, is critical for the correct patient management. It is important to recognize that PROP1 mutations can present associated with evolving pituitary masses and/or other MRI alterations of the pituitary during early childhood and that surgery is not indicated in these patients. Therefore, in the presence of combined pituitary hormone deficiency and a pituitary or hypothalamic mass, PROP1 analysis should be considered before referring the patient to a neurosurgeon.

Objective: Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls. Methods: One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol. Results: The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS. Conclusion: The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease.

Objective: The autonomic nervous system is assumed to have a role in the pathophysiology of obesity. In this study, we evaluated the autonomic system by measuring heart rate variability (HRV) in obese children. Methods: Thirty-two obese and 30 healthy children (mean ages: 11.6±2.0 years and 11.0±2.9 years, respectively) were enrolled in the study. Obesity was defined as a body mass index higher than 97th percentile for age- and gender-specific reference values. All participants were free of any disease and none of them was receiving any medication. Twenty-four-hour ambulatory electrocardiographic recordings were obtained and the time-domain and frequency-domain indices of HRV were analyzed. The study group was evaluated with respect to insulin resistance by HOMA-IR values. Results: A significant decrease in calculated HRV variables was observed in obese children as compared to controls. The HRV alteration was found in both time-domain and frequency-domain parameters. The subgroup analysis of the study group revealed a significant decrease in all investigated HRV parameters in the insulin-resistant obese children compared to the non-insulin-resistant obese ones. Conclusions: Our results indicate that HRV is decreased in obese children, which implies parasympathetic withdrawal and sympathetic predominance. A marked decrease in HRV was observed in insulin-resistant obese children compared to their non-insulin-resistant counterparts. We propose that autonomic imbalance pertaining especially to insulin resistance may be involved in the pathogenesis of obesity in pediatric patients Conflict of interest:None declared.

Background/Aims: Plant growth regulators are considered to leave minimal amounts of remnants and therefore cause no significant side effects in humans. In this study, we aimed to investigate the hormonal and histopathological effects of 4-chlorophenoxy acetic acid (4-CPA), a commonly used plant growth regulator, on the gonadal functions of rats. Methods: The study was implemented on 64 Wistar albino rats (20 days old). Forty-eight rats received 4-CPA every day until 50 days of age. The rats were randomized into 4 groups (a control group and three 4-CPA groups with doses of 25, 50 and 100 mg/kg/day); each group was further divided into males and females, making a total of 8 groups. The levels of FSH, LH, testosterone, estradiol, leptin, inhibin-B and neuropeptide-Y were measured. Histopathological examination of the testes and ductus deferens in male rats, and ovaries and uterus of female rats (caspase-3 and -9 immunoreactivity) was performed. Results:Although hormone levels were similar between the groups, rats that received 4-CPA showed significantly higher degrees of apoptosis compared to the control group (p < 0.001) and increased doses of 4-CPA were directly correlated with the amount of apoptosis (p < 0.001). Conclusion: 4-CPA induced apoptosis in the gonads of rats without concurrent changes in plasma hormone levels.

Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318) T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318) T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318) T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.

To investigate metabolic syndrome (MetS) and MetS criteria, and to establish whether metabolic syndrome criteria were associated with non-alcoholic fatty liver disease (NAFLD) in obese children.A total of 451 pubertal obese children (8-18 years old) were enrolled in the study. Patients were divided into three groups according to the degree of steatosis. Antropometric and laboratory measurements of the participants were recorded.Of 451 obese children, 217 (48.1%) were diagnosed as having NAFLD and 96 (21.3%) as having MetS. The frequency of abdominal obesity, hypertension, impaired fasting glucose, hyperinsulinemia, dyslipidemia and type 2 diabetes mellitus (T2DM) were 61.8% (279), 25.7% (116), 4.4% (20), 54.3% (245), 41% (185) and 2.2% (10), respectively. The prevalence of NAFLD among patients with MetS [73% (70/96)], was significantly higher than the frequency of hypertension [55% (53/96)] and abnormalities of glucose metabolism [23% (22/96)], but almost equal to the frequency of dyslipidemia [78% (75/96)]. The prevalence of MetS criteria were higher in patients with NAFLD than those without NAFLD. Except impaired fasting glucose, blood pressure and T2DM significant difference was found between groups for all. It was observed that the number of MetS criteria increased in parallel with the severity of steatosis.NAFLD in obese children is strongly associated with multiple MetS criteria. In addition to NAFLD is not only a liver disease, but also early mediator that reflects metabolic disorder, and liver ultrasound can be a useful tool for MetS screening.

A 5-year-old child with precocious puberty and complete masculinization of the genitalia was diagnosed to have 21-hydroxylase deficiency. The patient was also found to have a prostate gland and increased prostate-specific antigen. The presence of a prostate and its relation to prostate-specific antigen and prostate adenocarcinoma are discussed in the light of the relevant literature.

Aim: To investigate the relationship of adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease (NAFLD). Patients & methods: Group I consisted of 63 obese children with liver steatosis, group II consisted of 12 obese children with elevated serum ALT activity from group I, and group III included 85 obese children without liver steatosis. Results: Leptin levels were higher in the NAFLD children than in the control group. Serum RBP4 levels in obese children with NAFLD were higher than those in obese children without NAFLD and controls. Adiponectin and resistin levels were negatively correlated and RBP4 levels positively correlated with ALT activity and ultrasonographic grading. Conclusion: These data suggest that adiponectin, resistin and RBP4 may have a role in the pathogenesis of NAFLD in obese children. Adiponectin, leptin, resistin and RBP4 may be suitable markers for predicting metabolic syndrome and NAFLD.

Aim: To investigate the relationship between serum adiponectin, resistin and RBP4 levels and the components of metabolic syndrome. Patients & methods: Serum adiponectin, resistin and RBP4 levels were detected and analyzed in 148 8–18-year-old Turkish obese pubertal children with/without metabolic syndrome. Results: Adiponectin and resistin concentrations were significantly inversely correlated with BMI standard deviation score, homeostatic model assessment insulin resistance, waist circumference, triglyceride levels and diastolic and systolic blood pressure, and were directly correlated with high-density lipoprotein cholesterol. RBP4 concentrations were directly correlated with homeostatic model assessment insulin resistance, waist circumference, triglyceride levels and diastolic and systolic blood pressure, and inversely correlated with high-density lipoprotein cholesterol. Conclusion: Adiponectin, RBP4 and, in particular, resistin levels may be used as suitable predictive biomarkers of metabolic syndrome.

BACKGROUND In obese populations, oxidative stress plays a major role in the pathogenesis of serious diseases such as diabetes, coronary heart disease, and atherosclerosis. In this study, we investigated the status of oxidative stress in obese children as to nitrite/nitrate and glutathione peroxidase levels, and their relation with insulin resistance (IR). METHODS A total of 63 obese children were enrolled in the study. Each was relegated to one of three groups: 20 obese children without IR (11 adolescents, 9 prepubertal; mean age 10.27 +/- 2.36 years; 10 males, 10 females), 22 obese children with IR (13 adolescents, 9 prepubertal; mean age 11.26 +/- 2.52 years; 10 males, 12 females), and a control group of 21 children (14 adolescents, 7 prepubertal; mean age 11.41 +/- 2.00 years; 10 males, 11 females). RESULTS Glutathione peroxidase levels were lower in the obese group with IR than in either the control group or the obese group without IR (0.032 +/- 0.01 vs. 0.048 +/- 0.01 and 0.042 +/- 0.01, respectively). Nitrite/nitrate levels were higher in the obese group with IR than in the control group or the obese group without IR (89.83 +/- 25.00 vs. 66.00 +/- 21.75, and 68.65 +/- 28.98, respectively) and compared by pubertal status, adolescents' results were similar. However, in prepubertal children, nitrite/nitrate and glutathione peroxidase levels were not significantly different between groups. Multiple regression analysis revealed that nitrite/nitrate levels were positively correlated with the homeostasis model assessment of IR (HOMA-IR) independent of body mass index, age, gender, serum lipids, and pubertal stages, and that glutathione peroxidase levels were negatively correlated with body mass index and HOMA-IR independent of age, gender, pubertal status, and serum lipids. CONCLUSION This study demonstrates that oxidative stress exists even in populations of obese children, and that oxidative stress markers have a relation with the HOMA-IR, which was used as a surrogate marker of IR.

Osteoprotegerin (OPG)/“receptor activator of nuclear factor kappa B-ligand” (RANKL) system has an important role in the remodeling of bone through regulation of osteoclastogenesis. We aimed to detect OPG and RANKL levels, particularly in obese children in the pubertal period and to investigate whether these parameters correlate with insulin resistance in childhood. Our study included 66 obese children ranging in age from 9.1 to 16 years, and 22 non-obese children ranging in age from 10.5 to 16 years. Blood glucose, insulin, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured for all cases; HOMA-IR, Quicki index and atherogenic index were calculated. Serum OPG and RANKL levels were also measured. OPG and RANKL levels did not show any difference between obese and non-obese children (P>.05). No difference in these 2 parameters were observed among the children with and without insulin resistance (P>.05). No correlation could be established between the OPG, the HOMA-IR, Quick and atherogenic indices. Obesity and insulin resistance are believed to show their effect in the later period of life to become able to change some of the parameters.