The Effects of Long-term Growth Hormone Treatment on Ocular Findings.

PURPOSE: This study aimed to examine the long-term changes in anterior chamber depth (ACD), central corneal thickness (CCT), axial length (AxL), peripapillary retinal nerve fibre layer thickness (RNFLT), peripapillary ganglion cell layer - inner plexiform layer (GCL-IPL) thickness, and peripapillary choroidal thickness (ChT) after rhGH replacement treatment in paediatric patients with IGHD, compared to healthy controls. METHODS: Twenty-two children with IGHD including 12 girls and 10 boys were enrolled in the study group, and 30 (16 girls, 14 boys) healthy children composed the control group. A detailed ophthalmological examination was performed for each participant. ACD, CCT, AxL, peripapillary RNFLT, GCL-IPL thickness and ChT measurements were performed before the rhGH replacement treatment and in the 12th month of the post-treatment period, as well as the corresponding visits in the control group. AxL ultrasound pachymetry (CCT), peripapillary RNFL thickness, peripapillary RNFLT, GCL-IPL thickness, and peripapillary ChT parameters were measured by spectral-domain optical coherence tomography. RESULTS: The mean age of the groups were similar (p = 0.143). 12-month CCT, ACD, and AxL measurements of the study group showed significantly higher results than the pre-treatment measurements (p = 0.005, p = 0.024, and p = 0.002, respectively). Similarly, the mean RNFLT and ChT measurements of the study group obtained from all sectors were significantly higher in the 12th-month visit (p < 0.001 for both) other than the RNFLT, and GCL-IPL thickness measurements (p > 0.05 for all). However, all these parameters were similar at pre- and post-treatment visits in the control group (p > 0.05 for all). The mean pre-treatment values of all these parameters were significantly lower in the study group compared to the control group (p < 0.05 for all), other than the RNFLT, GCL-IPL thickness measurements (p > 0.05 for all), while the mean post-treatment values of all these parameters in both groups were similar at month 12 (p > 0.05 for all). CONCLUSION: GH replacement treatment in childhood may play an important role in the development of the neural retina and can be effective on the anterior segment, RNFLT and ChT measurements.

Study of ten causal genes in Turkish patients with clinically suspected maturity-onset diabetes of the young (MODY) using a targeted next-generation sequencing panel.

BACKGROUND: Maturity-onset diabetes of the young (MODY), which is the most common cause of monogenic diabetes, has an autosomal dominant pattern of inheritance and exhibits marked clinical and genetic heterogeneity. The aim of the current study was to investigate molecular defects in patients with clinically suspected MODY using a next-generation sequencing (NGS)-based targeted gene panel. METHODS: Candidate patients with clinical suspicion of MODY and their parents were included in the study. Molecular genetic analyses were performed on genomic DNA by using NGS. A panel of ten MODY-causal genes involving GCK, HNF1A, HNF1B, HNF4A, ABCC8, CEL, INS, KCNJ11, NEUROD1, PDX1 was designed and subsequently implemented to screen 40 patients for genetic variants. RESULTS: Ten different pathogenic or likely pathogenic variants were identified in MODY-suspected patients, with a diagnostic rate of 25%. Three variants of uncertain significance were also detected in the same screen. A novel pathogenic variant in the gene HNF1A (c.505_506delAA [p.Lys169AlafsTer18]) was described for the first time in this report. Intriguingly, we were able to detect variants associated with rare forms of MODY in our study population. CONCLUSIONS: Our results suggest that in heterogenous diseases such as MODY, NGS analysis enables accurate identification of underlying molecular defects in a timely and cost-effective manner. Although MODY accounts for 2-5% of all diabetic cases, molecular genetic diagnosis of MODY is necessary for optimal long-term treatment and prognosis as well as for effective genetic counseling.

Association of diabetic ketoacidosis and HbA1c at onset with year-three HbA1c in children and adolescents with type 1 diabetes: Data from the International SWEET Registry.

OBJECTIVE: To establish whether diabetic ketoacidosis (DKA) or HbA1c at onset is associated with year-three HbA1c in children with type 1 diabetes (T1D). METHODS: Children with T1D from the SWEET registry, diagnosed <18 years, with documented clinical presentation, HbA1c at onset and follow-up were included. Participants were categorized according to T1D onset: (a) DKA (DKA with coma, DKA without coma, no DKA); (b) HbA1c at onset (low [<10%], medium [10 to <12%], high [≥12%]). To adjust for demographics, linear regression was applied with interaction terms for DKA and HbA1c at onset groups (adjusted means with 95% CI). Association between year-three HbA1c and both HbA1c and presentation at onset was analyzed (Vuong test). RESULTS: Among 1420 children (54% males; median age at onset 9.1 years [Q1;Q3: 5.8;12.2]), 6% of children experienced DKA with coma, 37% DKA without coma, and 57% no DKA. Year-three HbA1c was lower in the low compared to high HbA1c at onset group, both in the DKA without coma (7.1% [6.8;7.4] vs 7.6% [7.5;7.8], P = .03) and in the no DKA group (7.4% [7.2;7.5] vs 7.8% [7.6;7.9], P = .01), without differences between low and medium HbA1c at onset groups. Year-three HbA1c did not differ among HbA1c at onset groups in the DKA with coma group. HbA1c at onset as an explanatory variable was more closely associated with year-three HbA1c compared to presentation at onset groups (P = .02). CONCLUSIONS: Year-three HbA1c is more closely related to HbA1c than to DKA at onset; earlier hyperglycemia detection might be crucial to improving year-three HbA1c.

The prevalence of goiter and hypothyroidism among school children 6 years after introduction of a mandatory salt iodination program in a severely iodine-deficient area of the West Black Sea region of Turkey.

The objective of the current study was to determine the prevalence and the degree of iodine deficiency after mandatory salt iodization in Yigilca's school-aged children. A total of 806 school children aged 6-19 years were evaluated. The prevalence of goiter in children aged 6-12 and 13-19 years was 20.3 and 23.8%, respectively. The prevalence of hypothyroidism in children aged 6-12 and 13-19 years was 10.4 and 18.9%, respectively. The median serum free tetraiodothyronine (fT4) levels in children aged 6-12 and 13-19-years were 1.16 ng/dL and 0.91 ng/dL, respectively. The median urinary iodine concentration levels in children aged 6-12 and 13-19 years were 83 µg/l and 78 µg/l, respectively. The frequency of autoimmune thyroid disease was 2.1% in Yigilca's SAC. Goiter and iodine deficiency problems remain in rural areas of the West Black Sea Region of Turkey.

Evaluation of the systemic-immune inflammation index (SII) and systemic immune-inflammation response index (SIRI) in children with type 1 diabetes mellitus and its relationship with cumulative glycemic exposure.

OBJECTIVES: In this study, the systemic proinflammatory status was assessed using the systemic immune-inflammation index (SII) and SIRI systemic immune-inflammatory response index (SIRI) in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: The study involved 159 patients aged between 6 and 16 years. The SII and SIRI values were calculated based on the complete blood count. Basic blood biochemistry evaluated, and carotid intima-media thickness (cIMT) was measured and recorded. The cumulative glycemic exposure was calculated by multiplying the value above the normal reference range of the HbA1c value. The sum of all these values obtained from the time of diagnosis to obtain the cumulative glycemic exposure. All findings were compared statistically. All statistically significant parameters were evaluated in the multivariate logistic regression analysis. RESULTS: The analysis revealed that only cIMT (Exp(B)/OR: 0.769, 95 % CI: 0.694-0.853, p<0.001), high-density lipoprotein (Exp(B)/OR: 3.924, 95 % CI: 2.335-6.596, p<0.001), monocyte count (Exp(B)/OR: 1.650, 95 % CI: 1.257-2.178, p<0.001), hematocrit (Exp(B)/OR: 0.675, 95 % CI: 0.523-0.870, p<0.001), and SIRI (Exp(B)/OR: 1.005, 95 % CI: 1.002-1.008, p<0.001) were significantly associated with T1DM. A statistically significant positive association was found between cumulative glycemic exposure and SIRI only (r=0.213, p=0.032). To our knowledge, this is the first study to evaluate SII and SIRI in children with type 1 diabetes. CONCLUSIONS: These findings indicate that SIRI could serve as a potential biomarker for detecting early-onset proatherosclerotic processes in diabetic children. However, further clinical studies are required to confirm this.

Low-carb Diet in Hospitalized Late Pubertal Type 1 Diabetic Girls: A Short-Term CGM Study.

OBJECTIVE: We conducted the present study to observe potential short-term benefits or risks of low-carb diet (LCD). METHODS: This is a prospective randomized cross-over study. Type 1 diabetic girls were hospitalized in ternary groups for 7 days and each group randomly started with LCD or regular diet. Continuous glucose monitoring (CGM) was performed between 0 and 168 h. RESULTS: Twenty-eight subjects completed the study. Total energy, protein, and fat consumption were high (P < 0.001); carbohydrate consumption and rapidly acting insulin dose were low (P < 0.001 and P = 0.002, respectively) during LCD. Morning postprandial, noon postprandial, and evening preprandial capillary blood sugar levels were lower during LCD (P = 0.013, 0.018, and 0.048, respectively). CONCLUSION: LCD may have the advantage of better glycemic control despite lower insulin dose which is a favorable outcome with regard to weight control and atherosclerosis prevention. No adverse events were observed.

The relationship between particulate matter and childhood respiratory complaints and peak expiratory flows in Harran agricultural area.

BACKGROUND: In recent years, many studies have evaluated the increasing incidence of asthma and chronic respiratory diseases among children living close to rural areas with pesticide application. Pesticide exposure in 266 children (126 girls and 140 boys) in Sanliurfa, a cotton-producing province in Turkey, was explored in this work. Four different villages spread over 40 km2 were included. METHODS: Measurements of peak expiratory flow (PEF) in 266 children were conducted in late June, before intensive pesticide applications in the cotton-producing fields. The measurements were repeated for 72 of 266 children after pesticide application in late August. PEF, particulate matter with diameter less than 2.5 µm (PM < sub > 2.5 < /sub > ), particulate matter with diameter less than 10 µm (PM < sub > 10 < /sub > ), temperature, humidity, and wind speed were measured. RESULTS: After pesticide application, mean PM < sub > 2.5 < /sub > and PM < sub > 10 < /sub > values were significantly increased compared to before pesticide application (p < 0.001 for both parameters). After pesticide exposure, nasal discharge, sneezing, burning and itching in the eyes, cough, sputum production, wheezing, shortness of breath and chest tightness were significantly increased (p < 0.001). The mean PEF value was demonstrated to decrease significantly after pesticide application (p < 0.001). Moreover, significant negative correlations were noted between PEF and PM < sub > 10 < /sub > and between PEF and PM < sub > 2.5 < /sub > (p < 0.001). CONCLUSIONS: Intensive pesticide application causes respiratory dysfunction and increased respiratory complaints in children living near the affected agricultural areas, and impacts quality of life adversely. The results of this work can be used to develop an early warning system and methods to prevent respiratory disorders in children residing in the study area.

Internipple Distance and Internipple Index in Prepubertal Turkish Girls

Objective: To determine internipple distance and internipple index in prepubertal Turkish girls. Methods: The internipple distance and chest circumference of 667 healthy prepubertal Turkish girls aged 6 to 11 years were measured in a school screening program in Düzce. Measurements were performed at the end of expiration with a standard non-stretch tape measure graduated in millimeters with the arms hanging in a relaxed position on the sides of the body. The internipple distance was measured between the centers of both nipples, and chest circumference was measured across the internipple line. The internipple index was calculated by dividing the internipple distance (cm) x100 by the chest circumference (cm). Age specific internipple index reference curves were constructed and smoothed with the Lambda-Mu-Sigma method. Mean and standard deviations of internipple distance and internipple index were calculated according to decimal ages. Results: Age was found to be positively correlated with internipple distance and chest circumference, while it was negatively correlated with internipple index. The reference values of internipple index, including 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles, and standard deviations were calculated for prepubertal girls. Conclusion: The reference ranges provided by this study might be helpful for the evaluation of syndromic cases by serving as normative data for internipple index in prepubertal girls aged 6-11 years in Turkey although ethnic differences may affect applicability to other countries.

Serum 25-hydroxyvitamin D is associated with insulin resistance independently of obesity in children ages 5-17.

AIM: To determine the association of vitamin D with insulin resistance and obesity in children. METHODS: A total of 92 obese and 58 non-obese children aged 5-17 years were evaluated. Data were collected related to anthropometric (weight, height), and biochemical parameters (fasting plasma glucose, serum insulin, serum 25-hydroxyvitamin D, lipid profile, vitamin B12, parathormone) and physical examination (blood pressure, acanthosis nigricans, stria, lipomastia). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA). HOMA-IR = fasting insulin level (µU/ml) × fasting glucose (mg/dL)/405. A HOMA-IR value >2.5 was defined as insulin resistance. RESULTS: According to the US Endocrine Society classification, vitamin D deficiency (0-20 ng/ml) was determined at significantly higher rates in the obese group than in the control group (p < 0.001). The rate of subjects with a vitamin D level of 20-30 ng/ml was significantly lower in the obese group than in the control group (p < 0.001) Within the obese group a statistically significant difference was determined between the insulin resistant and non-insulin resistant groups in respect of serum 25-hydroxyvitamin D levels (p = 0.001) and vitamin B12 levels (p = 0.001). A significant negative correlation was determined between serum 25-hydroxyvitamin D and HOMA-IR (r=-0.256, p = 0.016) and insulin (r = -0.258, p = 0.015). The systolic blood pressure (p = 0.001) and diastolic blood pressure (p = 0.003) values were significantly different in the control and obese groups. A statistically significant difference was determined between the control and obese groups in terms of the levels of insulin, HOMA-IR, HbA1c, cortisol, LDL, total cholesterol, HDL, triglyceride, hemoglobin, MCV, MPV, and calcium. CONCLUSION: The prevalence of vitamin D deficiency was higher in obese children compared to normal-weight and overweight children. Serum 25(OH)D levels showed a negative correlation with insulin and HOMA-IR. Serum 25(OH)D is associated with insulin resistance independently of obesity.

Genotype-Phenotype Characteristics of Turkish Children With Glucokinase Mutations Associated Maturity-Onset Diabetes of the Young.

OBJECTIVE: To investigate phenotype-genotype correlations in Turkish children with glucokinase gene mutations leading to Maturity-onset diabetes in young (GCK-MODY). METHODS: Retrospective analysis of 40 patients (16 girls) aged under 18 with GCK-MODY. RESULTS: Mean (SD) serum fasting blood glucose level was 6.79 (0.59) mmol/L and the mean (SD) HbA1c level at diagnosis was 6.3% (0.5). Sixteen different variations were detected in the GCK genes of the 40 cases; 33 missense mutations, 6 deletions, and one nonsense mutation. The birthweight of infants with deletion mutation was significantly lower than that of infants with other mutations [2460 (353.66) g vs 2944.11 (502.08) g]. CONCLUSION: GCK-MODY patients with deletion mutation inherited from mothers had lower birthweight and higher fasting blood glucose than those with other inherited mutations but similar HbA1c values.

A family with novel homozygous deletion mutation (c.1255delT; p.Phe419Serfs*12) in the glucokinase gene, which is a rare cause of permanent neonatal diabetes mellitus.

Heterozygous inactivating mutations in the glucokinase gene cause the mildest form of maturity-onset diabetes of the adolescents. However, homozygous or compound heterozygous mutations in the glucokinase gene are a rare cause of permanent neonatal diabetes mellitus. Herein, we present the case of a male child with permanent neonatal diabetes mellitus whose mutational analysis revealed a novel homozygous deletion mutation in the glucokinase gene. The male proband of Turkish ancestry from consanguineous parents was born at 37 weeks gestation with a birth weight of 1870 g (<3rd percentile). Hyperglycemia developed during the first postnatal day and diabetes-related autoantibodies were negative. He was put on insulin on the first day of life. Insulin has never been discontinued since then. The mother was aged 35 years and had gestational diabetes. The father and the two brothers had impaired fasting glucose. Both parents and brothers were heterozygous for this mutation.

Bioelectrical impedance analysis of body fatness in childhood congenital adrenal hyperplasia and its metabolic correlates.

There is a tendency to adiposity in patients with congenital adrenal hyperplasia (CAH) despite physiological corticosteroid doses. This study investigated body fatness in children with CAH under corticosteroid replacement therapy. Seventeen children with CAH (female:male, 9:8; age range 1.6-10.5 years) and 18 controls (female:male, 9:9; age range 1.4-10.2 years) were studied. Serum lipids, leptin, insulin, anthropometry, body circumferences, skinfold thickness, and body fat ratio as measured with bioelectrical impedance analysis (BIA) were the study parameters. Weight standard deviation scores (SDS), body mass index (BMI), BMI-SDS, body circumferences, skinfold thickness, and body fat ratio were higher and leptin was positively correlated with all of the body circumference and skinfold thickness parameters as well as body fat ratio in the study group. Waist/hip ratio was lower in the study group. Body fatness is a serious problem starting in early childhood in CAH patients and further refinement of the glucocorticoid replacement regimens as well as lifestyle measures are needed.

Adult height in Turkish patients with Turner syndrome without growth hormone treatment.

Spontaneous adult height (AH) in Turner syndrome (TS) varies among populations. Population-specific AH data is essential to assess the efficacy of growth-promoting therapies in TS. A multicenter study was performed to establish AH of nongrowth hormone (GH)-treated Turkish patients with TS. One hundred ten patients with TS (diagnosed by karyotype) who reached AH (no growth in the previous year, or bone age > 15 years) without receiving GH treatment were included in the study. The average AH was found to be 141.6 +/- 7.0 cm at the age of 22.9 +/- 6.2 years, which is 18.4 cm below the population average and 16.4 cm below the patients' mid-parental heights. Bone age at start of estrogen replacement was 12.3 +/- 1.3 year. Karyotype distribution of the patients was 45X (43%), 45X/46XX (16%), 45X/46Xi (12%), 45XiXq (10%) and others (19%). When the patients were evaluated according to their karyotype as 45X and non-45X, no significant difference in AH was observed (142.4 +/- 6.9 cm vs 140.9 +/- 7.1 cm, respectively). Adult height of non-GH-treated Turkish TS patients obtained in this study was comparable to that of other Mediterranean populations, but shorter than that of Northern European patients. Karyotype does not seem to affect AH in TS.

Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency.

Valtropin is a recombinant human GH (rhGH) manufactured using a novel yeast expression system, classed as a 'biosimilar'. Valtropin was compared with Humatrope in children with GH deficiency (GHD). Treatment-naive, prepubertal children with GHD were randomized to Valtropin (n = 98) or Humatrope (n = 49) for 1 year. Standing height was measured 3-monthly and height velocity (HV) calculated. Serum IGF-I, IGFBP-3 and GH antibodies were determined centrally. HV at 1 year was 11.3 +/- 3.0 cm/year with Valtropin and 10.5 +/- 2.8 cm/year with Humatrope. Treatment difference was 0.09 cm/year with 95% confidence limits of -0.71, 0.90, within the preset non-inferiority limit of -2.0 cm/year. Height standard deviation (SD) scores were increased in both treatment arms with no acceleration of bone maturation. IGF-I and IGFBP-3 were increased comparably for both treatments. Adverse events showed no clinically relevant differences between treatment groups. Anti-GH antibodies were detected in 3 (3.1%) Valtropin and 1 (2.0%) Humatrope patients and the growth pattern was indistinguishable from the rest of the cohort. The 1-year efficacy and safety profile of Valtropin, a new biosimilar rhGH, are equivalent to the comparator rhGH, Humatrope. Valtropin can be used for the treatment of children with GHD and longer term data will fully establish its efficacy and safety profile.

Effects of growth hormone on growth, insulin resistance and related hormones (ghrelin, leptin and adiponectin) in Turner syndrome.

BACKGROUND: Concomitant evaluation of the metabolic and growth-promoting effects of growth hormone (GH) therapy in Turner syndrome (TS) may be used in the prediction of the growth response to GH therapy. AIM: To evaluate the metabolic effects of GH therapy in TS and correlation with the short-term growth response. PATIENTS: 24 prepubertal children with TS, aged 9.4 +/- 2.6 years were followed for auxology and IGF-I, IGFBP-3, leptin, ghrelin, adiponectin, lipids and OGTT results in a prospective multicenter study. INTERVENTION: GH (Genotropin) in a dose of 50 microg/kg/day for 1 year. RESULTS: Height standard deviation score (SDS) increased from -3.9 +/- 1.5 to -3.5 +/- 1.4 (p = 0.000) on therapy. BMI did not change. IGF-I SDS increased from -2.3 +/- 0.4 to -1.6 +/- 1.1 at 3 and 6 months (p = 0.001) and decreased thereafter. Serum leptin decreased significantly from 2.3 +/- 3.9 to 1.7 +/- 5.3 ng/ml (p = 0.022) at 3 months and increased afterwards. Serum ghrelin decreased from 1.2 +/- 0.8 to 0.9 +/- 0.4 ng/ml (p = 0.005) with no change in adiponectin. Basal and stimulated insulin levels also increased significantly. Delta height SDS over 1 year showed a significant correlation with Delta IGF-I(0-3 months) (r = 0.450, p = 0.027). CONCLUSION: IGF-I may be considered as a marker of growth response in TS at short term. Leptin shows a decrease at short term but does not have a correlation with growth response. The decrease in ghrelin in face of unchanged weight seems to be associated with increase in IGF-I and insulin levels. The unchanged adiponectin levels in spite of an increase in insulin levels indicates that adiponectin is mainly affected by weight, not insulin.

Serum levels of ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol in prepubertal children with iron deficiency.

The aim of the present study is to investigate possible alterations in ghrelin and other hormone levels related to appetite and somatic growth in children with iron deficiency anemia. Twenty-five patients and 25 healthy controls that were prepubertal and within normal limits regarding height and BMI standard deviation scores were recruited. Ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol levels were studied. Ghrelin, insulin and IGF-I levels were significantly low in the study group (ghrelin 13.58 +/- 16.32 vs. 35.39 +/- 23.69 ng/ml, p<.001; insulin 3.41 +/- 2.42 vs. 5.67 +/- 1.09 mU/ml, p = .008 and IGF-I 126.94 +/- 92.82 vs. 203 +/- 105.1 ng/ml, p = .015). We concluded that low ghrelin and insulin levels might be causes of the appetite loss in iron deficiency and as a result of appetite loss and undernutrition as well as by direct effects they might be related with growth retardation, which could be also influenced by low IGF-I levels.

Evaluation of glucose intolerance in adolescents relative to adults with type 2 diabetes mellitus.

AIM: There is an increasing trend in the prevalence of type 2 diabetes mellitus (DM2) in childhood and adolescence, while positive family history of DM2 and obesity are the most important risk factors. To study the influence of family history and obesity on glucose intolerance in our country was the aim of this study. STUDY DESIGN AND METHODS: A total of 105 children and adolescents aged 10-18 years (mean 13.3 +/- 2.5 years) were included in the study. All children and adolescents were divided into three groups according to positive family history of DM2 and obesity, and an oral glucose tolerance test (OGTT) was performed for all. Prediabetes was defined as impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Insulin secretion and insulin resistance were estimated using the insulinogenic index; and the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda index, respectively. RESULTS: The prevalence of prediabetes was 15.2% in the whole group, while it was 25.5% in obese children who also had a positive family history of DM2. The frequency of hyperinsulinism was 57.1% in all groups. Prediabetic children had significant insulin resistance (HOMA-IR 11.5 +/- 7.1 and 4.1 +/- 6.4, respectively, p = 0.034). CONCLUSIONS: Obesity and glucose intolerance are also a problem in developing countries. The risk of prediabetes in children is highest in obese children who also have a positive family history of DM2. There is a need for a lifelong preventive program starting in childhood to avoid DM2 and decrease cardiovascular risk factors

True hermaphroditism with characteristics of Klinefelter's syndrome: a rare presentation.

True hermaphroditism, a very rare cause of intersex, is usually diagnosed during the newborn period in the course of evaluating ambiguous genitalia. As an exception we report an unusual case of a 14.5 year-old boy with phenotypically near-normal male genitalia and bilaterally descended gonads, who was seen for evaluation of gynecomastia and hematuria. His eunuchoid body habitus and mild mental retardation were compatible with Klinefelter's syndrome. He had a low level of free testosterone (15.2 pmol/l), and high level of estradiol (264.3 pmol/l) for his age. The patient was diagnosed as true hermaphroditism with 46,XX /47,XXY karyotype causing an ovotestis with inguinal uterus hernia in the left scrotum and a dysgenetic testis in the right scrotum.

Whole-exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome.

CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare, congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growth hormone (GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined. OBJECTIVE: We applied whole-exome sequencing (WES) to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk-characteristic clinical diagnostic findings of PSIS. DESIGN AND PARTICIPANTS: WES was applied to two affected and one unaffected siblings. RESULTS: WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G protein-coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell. CONCLUSION: Mutations of GPR161 may be implicated as a potential novel cause of PSIS.