Search

Background: Induction of puberty in boys with constitutional delay of growth and puberty (CDGP) through a short course of low-dose testosterone therapy indicates the critical interaction between testosterone and the androgen receptor (AR) during the activation and maturation of the hypothalamic-pituitary-gonadal axis at puberty onset. Previous studies have shown an inverse relationship between the CAG repeat length and the transactivation function or expression level of the AR gene., Objective: We aimed to investigate whether the AR CAG repeat polymorphism has any implications on pubertal delay., Subjects and Methods: Thirty-three male patients with CDGP were enrolled in the study group, while 53 age-matched healthy individuals who had entered puberty on time were included in the control group. The CAG repeat length was determined through direct DNA sequencing analysis., Results: The median chronological age of boys with CDGP was 14.2 (14.1-14.6) years, compared to 14.2 (13.65-14.8) years for healthy subjects (p = 0.5). In the CDGP group, 22 (66.7%) children had a family history of the condition. There was no significant difference between the groups in terms of AR CAG repeat length (median AR CAG repeat length: 21 (20-24.5) and 20 (20-24), respectively, p = 0.1). However, in boys with CDGP with a similar family history (n = 22), a significantly longer AR CAG repeat length was found compared to the control group (n = 53) (median AR CAG repeat length: 22 (20-25) and 20 (20-24), respectively, p = 0.03). The median AR CAG repeat length in boys without a family history was 21 (20-22) triplets. Although boys with a family history had a slightly longer AR CAG repeat length than those without, the difference was not statistically significant (p = 0.07). Additionally, no significant differences were observed between boys with non-familial CDGP and control subjects (p = 0.8). Furthermore, no significant differences in anthropometric characteristics or hormonal parameters were found when patients with CDGP were categorized by AR CAG repeat length quartiles., Conclusion: This is the first study to investigate the role of AR CAG polymorphism in the etiopathogenesis of CDGP. Our findings suggest that the AR CAG repeat length may be associated with familial CDGP., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases., Design: National, multicenter and retrospective study., Patients: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017., Measurements: Diagnostic tests of CD and tumour size., Results: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure., Conclusions: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery., (© 2023 John Wiley & Sons Ltd.)

Aim: We aimed to describe the clinical characteristics of patients with congenital combined pituitary hormone deficiency (CPHD) and evaluate the first-year growth responses of individuals with CPHD and isolated growth hormone deficiency (IGHD) in order to establish the influence of other hormone deficiencies on growth response., Patients and Methods: This retrospective study was conducted in four tertiary care centers in Turkey. The records of patients diagnosed with CPHD (n=39) and severe IGHD (n=50) were collected. Cases with acquired lesions or chronic diseases were not included in the study. Data are presented as median (interquartile range)., Results: Among 39 patients (13 females; 33%) with a diagnosis of CPHD, the majority of patients (64%) presented initially with combined deficits at baseline examination, whereas isolated deficiencies (36%) were less prevalent. Among all patients with GH deficiency, TSH, ACTH, FSH/LH, and ADH deficiencies were present in 94%, 74%, 44%, and 9% of patients, respectively. Patients with CPHD were diagnosed at a younger age (4.9 (8.4) vs. 11.6 (4.1), p<0.001, respectively) and had lower peak GH concentrations (0.4 (1.8) vs. 3.7 (2.9), p<0.001, respectively) than patients with IGHD. Patients with IGHD and CPHD had similar first-year growth responses (Δheight SD score of 0.55 (0.63) vs. 0.76 (0.71), respectively, p=0.45)., Conclusions: We established the nature and timing of numerous hormonal deficits emerging over time. We also identified that the existence of CPHD did not hinder growth response., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART., Method: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded., Results: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro)., Conclusion: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series., Competing Interests: Declaration of competing interest All authors declare that there is no financial or other potential conflict of interest. All authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objective: Multisystem inflammatory syndrome in children (MIS-C), associated with Coronavirus disease-2019, is defined as the presence of documented fever, inflammation, and at least two signs of multisystem involvement and lack of an alternative microbial diagnosis in children who have recent or current Severe acute respiratory syndrome-Coronavirus-2 infection or exposure. In this study, we evaluated thyroid function tests in pediatric cases with MIS-C in order to understand how the hypothalamus-pituitary-thyroid axis was affected and to examine the relationship between disease severity and thyroid function., Methods: This case-control study was conducted between January 2021 and September 2021. The patient group consisted of 36 MIS-C cases, the control group included 72 healthy children. Demographic features, clinical findings, inflammatory markers, thyroid function tests, and thyroid antibody levels in cases of MIS-C were recorded. Thyroid function tests were recorded in the healthy control group., Results: When MIS-C and healthy control groups were compared, free triiodothyronine (fT3) level was lower in MIS-C cases, while free thyroxine (fT4) level was found to be lower in the healthy group (p<0.001, p=0.001, respectively). Although the fT4 level was significantly lower in controls, no significant difference was found compared with the age-appropriate reference intervals (p=0.318). When MIS-C cases were stratified by intensive care requirement, fT3 levels were also lower in those admitted to intensive care and also in those who received steroid treatment (p=0.043, p<0.001, respectively)., Conclusion: Since the endocrine system critically coordinates and regulates important metabolic and biochemical pathways, investigation of endocrine function in MIS-C may be beneficial. These results show an association between low fT3 levels and both diagnosis of MIS-C and requirement for intensive care. Further studies are needed to predict the prognosis and develop a long-term follow-up management plan.

Objective: Although the sensitivity and specificity of bilateral inferior petrosal sinus sampling (BIPSS) were shown to be quite high in adult patients, pediatric studies are limited in number and have conflicting results, since BIPSS is much less commonly performed in children. The aim of this study was to assess the role of BIPSS in the detection and accuracy of lateralization of pituitary adenomas in pediatric patients with Cushing disease (CD) and its possible advantage over other diagnostic methods., Methods: This was a multicenter, nationwide, web-based study. The diagnostic value of BIPSS in 16 patients, aged between four and 16.5 years with a confirmed diagnosis of CD, was evaluated retrospectively. The sensitivity and specificity of BIPSS and magnetic resonance imaging (MRI) were calculated, and compared statistically., Results: Standard tests, except for morning cortisol level, were effective in proving the presence of Cushing syndrome. While MRI findings were consistent with microadenoma in eight cases (50%), CD presence and lateralization was successfully predicted in 14 of 16 patients using BIPSS. BIPSS compared with MRI examination was significantly more accurate, both in pre-stimulation and post-stimulation results (p=0.047 and p=0.041, respectively). BIPSS showed a significantly higher sensitivity (92.8%) than MRI in detecting the pituitary source of adrenocorticotropic hormone secretion., Conclusion: These results suggest that BIPSS is superior to MRI for diagnostic work-up to confirm the diagnosis of CD. Moreover, in line with previous studies, BIPSS was shown to provide better information about adenoma location, which is vital for possible surgical intervention.

Background: Current studies claim that peptides such as leptin, adiponectin, ghrelin, and nesfatin-1 found in breast milk may be responsible for the growth of infants. Therefore, we aimed to determine the association between breast milk total ghrelin and nesfatin-1 levels and anthropometric measurements of infants who were small for gestational age (SGA)., Methods: 20 SGA and 20 appropriate for gestational age (AGA) infants were enrolled in the study. Anthropometric measurements of infants were carried out at birth, 1st, and 4th months. In addition, total ghrelin and nesfatin-1 levels in the breast milk were concomitantly measured., Results: Total ghrelin at the 4th month in breast milk waslower-level in the SGA group (p=0.015). In both groups, nesfatin-1 levels at the 4th month were lower than the values at the 1st month. Additionally, nesfatin-1 levels of SGA infants at the 4th month were higher (p=0.035)., Conclusions: Breast milk total ghrelin and nesfatin-1 levels differed in both groups, and it is probably referred to the growth discrepancy of these infants during the first months of life. Furthermore, we consider that higher breast milk nesfatin-1 levels at the 4th month may be a preventive against obesity in SGA infants who have potential risk for obesity in childhood and adulthood.

Background: In this study, we aimed to evaluate the serum neurotensin (NT) levels and their relationships with self-reported anxiety, emotion regulation skills and impulsivity in healthy and obese adolescents., Methods: Adolescents who gained weight between 12- 17 years of age and who were above the 95th percentile (p) for body mass index (BMI) > 95p were compared with age- and gender-matched healthy adolescents with a BMI of 3-85 p. Anthropometric measurements were performed, and serum NT levels were analyzed with ELISA method in all participants. Barrat Impulsivity Scale-11 (BIS-11), Screen for Child Anxiety Related Disorders (SCARED) and Difficulties in Emotion Regulation Scale (DERS) were used for evaluating self-reported impulsivity, anxiety and emotion regulation. MANOVA with follow-up univariate ANOVAs (Bonferroni corrected) were used for group comparisons. P was set at 0.05 (two-tailed)., Results: Sixty-five obese and 65 healthy adolescents were included in the study. In the obese group, NT levels were significantly elevated compared to the control group. Self-reported emotion-regulation difficulties, anxiety and impulsivity were significantly elevated among obese adolescents. Serum NT levels among the obese group were positively correlated with emotion dysregulation and impulsivity scores., Conclusions: In this study, we found emotional dysregulation, anxiety, impulsivity, and serum NT levels were significantly elevated among obese adolescents compared to controls. NT levels in the obese group correlated with impulsivity and emotion dysregulation. Further studies should evaluate the potential role of NT in the etiology of psychopathology among adolescents who are obese.

Background/aim: We aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH)., Materials and Methods: Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system., Results: There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status., Conclusion: In this study, the CIMT values of CAH cases were similar to those of healthy subjects., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objectives: Obesity is often the result of a high-calorie and unbalanced diet for a long time and can sometimes be associated with hyperphagia and eating disorders. Neurotensin (NT) is an anorexigenic peptide, which is secreted from the central nervous system and intestines, and increases intestinal fat absorption. In the literature, conflicting results regarding serum NT level in obesity and the relation of NT with metabolic parameters were reported. Besides, there is no data regarding the relation of NT with eating disorders or food preference in obese individuals. We aimed to evaluate the relation of serum NT level with metabolic parameters, hyperphagia, binge eating disorder (BED) and food preference in obese adolescents., Methods: The study included 65 obese adolescents and 65 healthy controls. Anthropometric measurements, biochemical analyzes and body fat analyzes were performed in all cases. Hyperphagia score, presence of BED and three-day food intake records were also evaluated., Results: NT level was significantly higher in obese adolescents than in controls and it was not associated with metabolic parameters, hyperphagia or food preference. In the obese group, NT level was not significantly different according to the presence of BED., Conclusions: Serum NT level is high in obese adolescents; however, it is not associated with metabolic parameters, hyperphagia, BED or food preference., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Copeptin, the C-terminal part of arginine-vasopressin, is increased in hypertensive adolescents and closely associated with metabolic syndrome (MS). We aimed to investigate whether serum copeptin can be used to differentiate masked hypertension (MHT) and MS, and the role of sodium intake, natriuretic peptide response and renin-angiotensin-aldosterone system in MHT and MS in obese youth., Methods: Obese children aged 10-18 years with normal office blood pressure measurements were included. Patients with MHT and normotension and those with MS and non-MS were evaluated separately. Biochemical parameters, copeptin, brain natriuretic peptide (BNP), aldosterone, renin, urine sodium, and protein were evaluated. Echocardiography, fundoscopic examination, and ambulatory blood pressure monitoring were performed., Results: There were 80 (M/F=39/41) obese patients with a mean age of 13.78 ± 1.93 years. The cases with MHT, MS, and concomitant MHT and MS were 53,24, and 13%, respectively. Copeptin levels were similar among patients with and without MHT or MS (p>0.05). However, multivariate analysis revealed that copeptin significantly increased the probability of MHT (OR 1.01, 95% CI=1.001-1.018, p=0.033). Copeptin was positively correlated with daytime systolic and diastolic load, aldosterone, BNP, and urine microalbumin/creatinine levels (p<0.05). Linear regression analyses revealed that copeptin was significantly correlated with BNP regardless of having MHT or MS in obese youth. In the MHT group, 24-h sodium excretion was not significantly correlated with BNP., Conclusion: Copeptin may be a beneficial biomarker to discriminate MHT, but not MS in obese children and adolescents. An insufficient BNP response to sodium intake might be one of the underlying causes of MHT in obese cases., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose: To determine early ocular changes in children and adolescents with type 1 diabetes mellitus without retinopathy (T1DM-woR) by optical biometry (OB) and optical coherence tomography (OCT)., Methods: Seventy children and adolescents with T1DM-woR (patient group) and 72 healthy children and adolescents (control group) were included. Demographic data, anthropometric measurements and anterior-posterior segment parameters of groups were compared. Correlations between ocular parameters and glycosylated hemoglobin (HbA1c) level, age at diabetes mellitus (DM) onset and DM duration were evaluated., Results: Patients with T1DM-woR had significantly shallower anterior chambers (3.50 ± 0.12 vs 3.67 ± 0.11 mm, p < 0.001), thicker lenses (3.65 ± 0.15 vs 3.37 ± 0.14 mm, p < 0.001), thinner central retinal nerve fiber layer (RNFL) thicknesses (95.3 ± 6.7 vs 104.8 ± 6.2 µm, p < 0.001) and thinner central choroidal thicknesses (292.8 ± 23.6 vs 325.1 ± 24.7 µm, p < 0.001) than healthy individuals. As the lens thickness (LT) increased, anterior chamber depth (ACD) decreased in patient group (r = - 0.368, p = 0.040). Other anterior (central corneal thickness, axial length, keratometry, spherical equivalent) and posterior (superior temporal, superior nasal, nasal, inferior nasal, inferior temporal, temporal RNFL thicknesses; nasal and temporal choroidal thicknesses; central part's and inner-outer macular segments' thickness and volume measurements) segment parameters of groups were similar (p > 0.05). In patient group, as HbA1c level increased, central RNFL and choroidal thicknesses decreased (r = - 0.639, p < 0.001; r = - 0.486, p = 0.010, respectively)., Conclusions: In patients with T1DM, we found that LT increased, and ACD, central RNFL and choroidal thicknesses decreased by OB and OCT before visible findings appeared in routine ophthalmological examination. Determination of early changes is warning to physician and patient in order to prevent more serious damages occurring later.

Objective: Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options., Methods: Here we present nationwide initial and follow-up data on HR., Results: From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed PHEX mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1 st , 2 nd and 3 rd year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1 st and 2 nd years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3 rd year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group., Conclusion: HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.

Objective: Turner syndrome (TS) is one of the most common chromosomal abnormalities and an important cause of short stature and infertility due to ovarian failure in females. The aim was to evaluate the knowledge of TS among physicians and parents of children with TS and to enhance awareness about this subject., Methods: One hundred and forty physicians were included in the study. The study population comprised 37 pediatricians (26.4%), 15 gynecologists (10.7%), 88 family physicians (62.9%) and 30 parents who had daughters with a diagnosis of TS. Two separate questionnaires were administered to evaluate TS knowledge of physicians and parents., Results: According to the self-reports of physicians, 49% had insufficient knowledge of TS, while 15.7% indicated that they had no knowledge of TS. The mean percentage of correct answers was 50.71±16.17% for all physicians. When the entire group of physicians was considered, 67.1% of them did not know the approximate incidence of TS, while 14.3% of them incorrectly indicated that TS was a condition that was seen in boys. The mean percentage of correct answers among parents was 68±15%, and there was no difference between the mothers’ and fathers’ correct answer rates (p=0.063). The majority of parents was not aware of TS-associated diseases and increased malignancy risk in TS., Conclusion: Physician knowledge of TS was poor and that there is a need for continued education about TS at the medical faculty and post-graduate levels.

Objective: Macular damage may be observed in obesity and metabolic syndrome (MetS), a condition which leads to chronic subclinical inflammation and affects most organ systems. To investigate the association between macular variability and anthropometric measurements, metabolic parameters, and inflammatory markers in children and adolescents with MetS., Methods: Two hundred and twenty eyes of 62 obese and 48 healthy children and adolescents were examined. Bilateral macular retinal thickness (MRT) and macular retinal volume (MRV) were measured in all subjects using optical coherence tomography. Associations between mean MRT and mean MRV and age, auxological measurements including body mass index standard deviation scores (BMI-SDS) and waist circumference-SDS (WC-SDS), metabolic parameters and inflammatory parameters including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio and systemic immune-inflammatory index (SIII) were investigated., Results: No statistically significant difference was observed between the groups in terms of age or sex distribution (p>0.05). Mean MRT (r=-0.326, p=0.007) and MRV (r=-0.303, p=0.007) values in the obese group with MetS decreased as homeostasis model assessment-insulin resistance (HOMA-IR) values increased. SIII values were higher in obese groups, but particularly in obese subject with MetS, compared to the control group (p=0.021). The decrease in mean MRT (r=-0.544, p=0.046) and MRV (r=-0.651, p=0.031) in the obese subjects with MetS was negatively correlated with NLR. Mean MRT and MRV decreased in all obese subjects as SIII increased (p<0.05)., Conclusion: This is the first study to show that mean MRT and MRV values decrease as BMI-SDS, WC-SDS and HOMA-IR increase in obese children and adolescents with MetS. NLR and SIII may serve as markers of chronic inflammation in obese children with MetS associated with macular damage.

Objective: Vitamin D-dependent rickets type 2A (VDDR2A) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor gene ( VDR ), leading to end-organ resistance to 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ). The objective of this study was to investigate VDR mutations in 11 patients from 8 Turkish-Arab families. Methods: All coding exons and intron-exon boundaries of the VDR gene were amplified by polymerase chain reaction from peripheral leukocyte DNA and sequenced. The effect of splice-site mutations on mRNA splicing was evaluated by a customized VDR mini-gene assay. Results: Homozygous VDR mutations were found in all the patients, including four novel mutations: c.473G>T (p.R158L), c.1-4A>G (IVS3-2A>G), c.755+1G>T, and c.352&#95;356delGACAG (p.D118Sfs*7). The c.1-4A>G mutation was located in the canonical splice acceptor site and 4 base pairs from the original ATG start codon. The mutation resulted in both complete (60% of transcripts) and partial exon 4 skipping (15% of transcripts). The latter was due to activation of a cryptic splice acceptor site and did not disrupt the open reading frame. Both c.755+1G>T and c.352&#95;356delGACAG resulted in frameshifts and a premature stop codon. Clinically, all the patients required continued treatment, except for patient IV-3, who presented with alopecia, hypocalcemia, and increased 1,25(OH) 2 D 3 at 1.5 years of age as a result of the c.1-4A>G mutation. He stopped taking medication at 6 years of age and still maintained normal height and biochemical profile. Conclusion: We have identified four novel VDR mutations. Although canonical splice-site mutations cause premRNA splicing errors that usually lead to a severe disease phenotype, mild disease can also occur due to activation of a cryptic splice site. Abbreviations: 1,25(OH) 2 D 3 = 1,25-dihydroxyvitamin D 3 (calcitriol); 25OHD 3 = 25-hydroxyvitamin D 3 ; PCR = polymerase chain reaction; PTH = parathyroid hormone; VDDR2A = vitamin D-dependent rickets type 2A; VDR = vitamin D receptor.

AimThe present study aimed to evaluate systolic and diastolic myocardial function in children and adolescents with congenital adrenal hyperplasia., Methods: The study included 44 children with the diagnosis of classic congenital adrenal hyperplasia and 39 healthy children whose age, pubertal status, and gender were similar to those of the patient group. Anthropometric parameters and 17-hydroxyprogesterone levels were measured, and bone age was calculated. The average daily hydrocortisone dose was calculated over the last 1-year file records. Hyperandrogenic state was defined according to bone age SD score (⩾2) and 17-hydroxyprogesterone levels (&gt;10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging., Results: Patients had higher morphological parameters, such as left ventricular end-systolic diameter, interventricular septal thickness at end diastole, left ventricular posterior wall thickness at end diastole, left ventricular mass and index, than the control group (p&lt;0.05). On pulsed-wave and tissue Doppler echocardiography, significant subclinical alterations were observed in systolic (isovolumic contraction time), diastolic (isovolumic relaxation time), and global left ventricular functional (myocardial performance index) parameters in the congenital adrenal hyperplasia group compared to the control group (p&lt;0.05). In partial correlation analyses, after controlling the effect of hyperandrogenism, the mean hydrocortisone dosage was positively correlated with isovolumic relaxation time in congenital adrenal hyperplasia group (p&lt;0.05)., Conclusion: This study demonstrated that the patients with congenital adrenal hyperplasia are at risk for left ventricular hypertrophy, systolic and diastolic myocardial subclinical alterations. Overtreatment may be responsible for the increased risk of myocardial dysfunction in patients with congenital adrenal hyperplasia.

It is difficult to make a diagnosis of adrenal insufficiency in the newborn, because the clinical findings are not specific and the normal serum cortisol level is far lower compared to children and adults. However, dehydratation, hyperpigmentation, hypoglycemia, hyponatremia, hyperkalemia and metabolic acidosis should suggest the diagnosis of adrenal insufficiency. Hypotension which does not respond to vasopressors should especially be considered a warning. If the adrenocorticotropin hormone level measured simultaneously with a low serum cortisol level is 2-fold higher than the upper normal limit of the reference range, a diagnosis of primary adrenal insufficiency is definite. Even if the serum cortisol level is normal, a diagnosis of relative adrenal insufficiency can be made with clinical findings, if the patient is under heavy stress. The serum cortisol level should be measured using the method of 'high pressure liquid chromatography' or 'LC mass spectrometry'. Adrenal steroid biosynthesis can be evaluated more specifically and sensitively with 'steroid profiling'. Rennin and aldosterone levels may be measured in addition to serum electrolytes for the diagnosis of mineralocorticoid insufficiency. Adrenocorticotropic hormone stimulation test may be used to confirm the diagnosis and elucidate the etiology. In suspicious cases, treatment can be initiated without waiting for the adrenocorticotropic hormone stimulation test. In schock which does not respond to vasopressors, intravenous hydrocortisone at a dose of 50-100 mg/m 2 or a glucocorticoid drug at an equivalent dose should be initiated. In maintanence treatment, the physiological secretion rate of hydrocortisone is 6 mg/m 2 /day (15 mg/m 2 /day in the newborn). The replacement dose should be adjusted with clinical follow-up and by monitoring growth rate, weight gain and blood pressure. Fludrocortisone (0,1 mg tablet) is given for mineralocorticoid treatment (2x0,5-1 tablets). A higher dose may be needed in the neonatal period and in patients with aldosterone resistance. If hyponatremia persists, oral NACl may be added to treatment. In the long-term follow-up, patients should carry an identification card and the glucocorticoid dose should be increased 3-10-fold in cases of stress., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background Maturity-onset diabetes of the young (MODY) is a common form of monogenic diabetes. Fourteen genes have been identified, each leading to cause a different type of MODY. The aims of this study were to reveal both known and novel variants in MODY genes in patients with MODY using targeted next generation sequencing (NGS) and to present the genotype-phenotype correlations. Methods Mutation analysis of MODY genes (GCK, HNF1A, HNF4A, HNF1B, ABCC8, INS and KCNJ11) was performed using targeted NGS in 106 patients with a clinical diagnosis of MODY. The variants were evaluated according to American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines recommendations. Results A total of 18 (17%) variants were revealed among all patients. Seven variants in GCK, six in HNF4A, four in HNF1A and one in ABCC8 genes were found. Eight of them were previously published and 10 of them were assessed as novel pathogenic or likely pathogenic variants. Conclusions While the most frequent mutations are found in the HNF1A gene in the literature, most of the variants were found in the GCK gene in our patient group using the NGS method, which allows simultaneous analysis of multiple genes in a single panel.

Background: To investigate serum levels of brain injury markers in diabetic ketoacidosis (DKA) and the relation of these markers with clinical and radiological findings of brain injury and laboratory results., Methods: Twenty-nine patients with DKA, 30 with type 1 diabetes mellitus (T1DM), and 35 healthy children were included. Clinical and laboratory findings, and the Glasgow Coma Scale (GCS) were recorded. In the DKA group, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) levels were measured at baseline and 6 and 12 hours after treatment. Magnetic resonance imaging was performed in the DKA group to demonstrate any brain injury., Results: No clinical or radiological findings of brain injury were found in any of the patients with DKA. In the DKA group, S100B was significantly higher than the healthy control and T1DM groups, while GFAP and NSE levels were not different from controls and T1DM patients. No significant differences were found in GFAP, NSE and S100B levels according to severity of DKA, diabetes duration and GCS., Conclusion: NSE and GFAP levels do not increase in DKA patients without overt brain injury. Elevated levels of S100B, which is also synthesized from non-neuronal tissues, might arise from peripheral sources. A lack of concurrent increase in serum levels of these brain injury markers might result from the yet intact blood brain barrier or a true absence of neuronal damage. In order to reveal subclinical brain injury related to DKA, there is a need for studies concurrently assessing neurocognitive functions., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: A comprehensive survey was conducted to evaluate the shortcomings of clinical care in patients with Turner syndrome (TS) in Turkey., Methods: A structured questionnaire prepared by the Turner study group in Turkey, which covered relevant aspects of patient care in TS was sent to 44 pediatric endocrinology centers., Results: Eighteen centers (41%) responded to the questionnaire. In the majority of the centers, diagnostic genetic testing, screening for Y chromosomal material, protocols regarding the timing and posology of growth hormone (GH) and estrogen, thrombophilia screening, fertility information and screening for glucose intolerance, thyroid, and coeliac diseases in patients with TS were in line with the current consensus. Thirteen centers (72.2%) performed GH stimulation tests. Only four centers (22.2%) used oxandrolone in patients with TS with very short stature. The majority of the centers relied on bone age and breast development to assess estrogen adequacy, though together with variable combinations of oestrogen surrogates. Two centers (11.1%) reported performing serum estradiol measurements. Eight centers (44.4%) routinely conducted cardiac/thoracic aorta magnetic resonance imaging. Screening for hearing, dental and ophthalmologic problems were performed by thirteen (72.2%), six (33.3%) and ten (55.6%) centers, respectively. Psychiatric assessments were made by four centers (22.2%) at diagnosis, with only one center (5.6%) requiring annual reassessments., Conclusion: Although we found some conformity between the current consensus and practice of the participating centers in Turkey regarding TS, further improvements are mandatory in the multi-disciplinary approach to address co-morbidities, which if unrecognized, may be associated with reduced quality of life and even mortality.

Background/aim: Nesfatin-1, an anorexigenic molecule, seems to play a role in appetite regulation and energy homeostasis. The goal of this study was to evaluate the relation of nesfatin-1 with anthropometric and metabolic (ghrelin, leptin) parameters in children with idiopathic chronic malnutrition. Materials and methods: The study included 37 underweight and 38 healthy children who were similar regarding age, sex, and pubertal status. Anthropometric and biochemical (nesfatin-1, ghrelin, and leptin levels) variables were assessed. Results: A total of 37 underweight subjects (mean age 10.5 ± 2.6 years) and 38 heathy subjects (mean age 10.3 ± 2.3 years) were recruited. Underweight children had significantly higher nesfatin-1 (2.76 ± 0.4 vs. 1.56 ± 0.7, P < 0.001) and lower leptin levels (2.21 ± 2.0 vs. 5.21 ± 2.4, P < 0.001) than those of the control subjects. Nesfatin-1 levels were significantly associated with only leptin levels, after adjusting for age and BMI (r = –0.371, P = 0.001). Conclusion: The present study is the first to evaluate nesfatin-1 levels in relation with anthropometric and metabolic parameters in children with chronic malnutrition, who were subsequently found to have significantly higher nesfatin-1 levels. Our study underlines that nesfatin-1 may play a role in the development of malnutrition by inhibiting food intake in children.

Objective: Obesity affects almost all systems in the body. This includes the retinal nerve fibers which may be damaged due to a chronic inflammatory process. To determine changes in retinal nerve fiber layer (RNFL) thickness in non-diabetic children and adolescents using optical coherence tomography (OCT) and to evaluate the relationship between this change, metabolic risk factors and pubertal stage., Methods: Thirty-eight obese and 40 healthy children and adolescents aged 10-18 years were included in the study. RNFL measurements from the optic disk and all surrounding quadrants were obtained using OCT from both eyes of the individuals in the study groups. Correlations between RNFL thickness and age, auxological measurements, pubertal stage, systolic and diastolic blood pressure, homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid values were investigated., Results: A general decrease was observed in RNFL thickness in obese subjects compared to the controls, the decrease being highest in the inferior quadrant, although these differences were not statistically significant (p>0.05). RNFL thickness was negatively correlated with body mass index (BMI) standard deviation score (SDS) in both groups (control group r=-0.345, p=0.029; obese group r=-0.355, p=0.022). Significant negative correlations were determined between diastolic blood pressure, HOMA-IR, low density lipoprotein cholesterol level and RNFL thickness (r=-0.366, p=0.024; r=-0.394, p=0.016; and r=-0.374, p=0.022, respectively) in the obese group, while there was no association between these parameters and RNFL thickness in the control group., Conclusion: In this cross-sectional study, no statistically significant difference in RNFL thicknesses between the obese and control groups was determined. However, RNFL thickness was found to decrease in both healthy and obese children as BMI-SDS values increased. Further prospective studies may be of benefit to determine whether the decrease in RNFL values might become more pronounced on long-term follow-up.

Objective: Increased glycemic variability (GV) is associated with increased oxidative stress, vascular complications, and mortality in metabolic syndrome (MS) and diabetes mellitus patients. To investigate the relationship between GV and inflammatory parameters in obese children with insulin resistance (IR) and to elucidate their effects on the development of MS., Methods: Fifty obese adolescents with IR were included in the study. All patients underwent anthropometric measurements, body fat analysis, and continuous glucose monitoring system (CGMS) for 24 hours. Serum lipids, adiponectin, and interleukin-6 (IL-6) levels were measured. GV coefficient (GVC) was calculated using the standard deviation and the average glucose value obtained by CGMS. IR was diagnosed according to the results of oral glucose tolerance test (OGTT). MS was diagnosed according to the modified World Health Organization and the International Diabetes Federation criteria., Results: Twenty-seven of the patients had MS and the remaining had only IR. Body fat mass, HbA1c, IL-6 levels, and peak insulin levels in the OGTT were significantly higher in the group with MS, but there was no difference in adiponectin levels. GVC was not different between the groups, but GVC significantly positively correlated with homeostasis model of assessment for IR, as well as with fasting, peak, and total insulin levels when all the patients were analyzed, while no significant relation was detected with adiponectin and IL-6 levels., Conclusion: This study suggests that GV is not different among obese adolescents with IR and MS. There seems to be a significant association between GV and IR parameters. However, other diagnostic criteria of MS (hypertension and/or dyslipidemia) or elevated IL-6 levels does not cause further increase in GV.

Objective: Stoss vitamin D treatment has been recommended for its non-skeletal benefits in adults, but there is a lack of data on the optimal dose of vitamin D stoss therapy in children with vitamin D deficiency/insufficiency without rickets. This study aimed to compare efficiency/side effects of two different stoss therapy regimens (10 000 IU/kg and 300 000 IU vitamin D3) administered in children with vitamin D deficiency/insufficiency without rickets., Methods: Sixty-four children who had vitamin D deficiency/insufficiency were studied. A serum 25-hydroxyvitamin-D (25-OH-D) level of 15-20 ng/mL was considered as vitamin D insufficient and <15 ng/mL was considered as vitamin D deficient. The patients were divided into two groups according to the stoss therapy doses they received. Serum calcium, phosphate, alkaline phosphatase, 25-OH-D, parathyroid hormone levels, and spot urine calcium/creatinine ratios before/after treatment were recorded. Wrist radiography and renal ultrasonography were performed., Results: The mean age of the subjects was 10.6±4.4 years. Thirty-two children were treated with a single vitamin D3 dose of 10 000 IU/kg and 32 patients received 300 000 IU. No difference was found in 25-OH-D levels between the two groups at presentation. The mean level of 25-OH-D was higher in the 10 000 IU/kg group at the second week of therapy. There was no difference between the groups at post-treatment weeks 4 and 12. The 25-OH-D was found to be below optimal levels (≥30 ng/mL) in 66.5% and <20 ng/mL in 21.8% of patients at the third month in both groups. None developed hypercalcemia and/or hypercalciuria. Nephrolithiasis was not detected in any patient., Conclusion: This study showed that both doses of stoss therapy used in the treatment of vitamin D insufficiency/deficiency are effective and safe. However, an optimal level of 25-OH-D cannot be maintained for more than three months.

Objective: To investigate the relationship between zonulin levels and clinical and laboratory parameters of childhood obesity., Methods: The study included obese children with a body mass index (BMI) >95 th percentile and healthy children who were of similar age and gender distribution. Clinical (BMI, waist circumferences, mid-arm circumference, triceps skinfold, percentage of body fat, systolic blood pressure, diastolic blood pressure) and biochemical (glucose, insulin, lipid levels, thyroid function tests, cortisol, zonulin and leptin levels) parameters were measured., Results: A total of 43 obese subjects (23 males, mean age: 11.1±3.1 years) and 37 healthy subjects (18 males, mean age: 11.5±3.5 years) were included in this study. Obese children had significantly higher insulin, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), zonulin and leptin levels than healthy children (p<0.05), while glucose levels were not different (p>0.05). Comparison of the obese children with and without insulin resistance showed no statistically significant differences for zonulin levels (p>0.05). Zonulin levels were found to negatively correlate with HDL-C and positively correlate with leptin levels, after adjusting for age and BMI., Conclusion: To the best of our knowledge, this is the first study investigating the relationship between circulating zonulin level (as a marker of intestinal permeability) and insulin resistance and leptin (as markers of metabolic disturbances associated with obesity) in childhood obesity. The results showed that zonulin was significantly higher in obese children when compared to healthy children, a finding indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances.

Objective: This study aimed to investigate the relationship between serum irisin level and metabolic and anthropometric parameters in obese children., Methods: The study included 36 obese children with a body mass index (BMI) of ≥95th percentile and 30 healthy children with a BMI ranging from the 5th to the 85th percentile. Healthy and obese children had similar age, gender and pubertal stage distribution. Anthropometric and biochemical parameters (fasting glucose, insulin, lipid profile, leptin and irisin levels) were measured. Bioelectric impedance analysis was used to determine the body composition parameters, including body fat percentage and fat mass., Results: Serum irisin and leptin levels of the obese children were significantly higher than those of the healthy children [median irisin levels, 141.2 & 107.6ng/mL, p=0.024; median leptin levels, 10.9 & 2.9pg/mL, P<0.001, respectively). No statistically significant difference was found when leptin and irisin levels were compared among obese patients in terms of the presence of insulin resistance. Irisin levels significantly correlated with high-density lipoprotein cholesterol (HDL-C), fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) with adjustment for age and BMI. The multivariate regression analysis showed that age, HOMA-IR and HDL-C had a significant association with the serum irisin level, which explained 30.6% of the variance., Conclusion: This study demonstrated that obese children had significantly higher irisin levels than healthy children. Additionally, it provides evidence regarding the role of irisin on insulin sensitivity and lipid metabolism in childhood obesity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Noonan syndrome (NS) is a multisystem disorder, and short stature is its most striking manifestation. Optimal growth hormone (GH) treatment for NS is still controversial. In this study, using a nationwide registration system, we aimed to evaluate the growth characteristics and the clinical features of NS patients in Turkey and their growth response to GH treatment., Methods: Children and adolescents with a diagnosis of NS were included inthe study. Laboratory assessment including standard GH stimulation test results were evaluated. Height increment of patients with or without GH treatment were analyzed after three years of therapy., Results: A total of 124 NS patients from different centers were entered in the web-based system. Short stature and typical face appearance were the most frequently encountered diagnostic features of our patients. Of the 84 patients who were followed long-term, 47 hadreceived recombinant human GH (rhGH). In this group of 47 patients, height standard deviation score (HSDS) increased from -3.62±1.14 to -2.85±0.96 after three years of therapy, indicating significant differences from the patients who did not receive GH treatment. PTPN11 gene was analyzed in 61 patients, and 64% of these patients were found to have a mutation. HSDS at admission was similar in patients with or without PTPN11 gene mutation., Conclusion: A diagnosis of NS should be kept in mind in all patients with short stature showing systemic clinical findings. GH therapy is effective for improvement of short stature especially in the first two years of treatment. Further studies are needed for optimisation of GH therapy and evaluation of final height data in NS patients.

Context: Recently several patients with resistance to thyroid hormone (RTH)-α due to T3 receptor-α (TRα) mutations were identified. The phenotype of these patients consists of varying degrees of growth impairment, delayed bone, mental and motor development, constipation, macrocephaly, and near-normal thyroid function tests., Objective: The objective of the study was to describe the clinical phenotype of three new families with RTHα and thereby gain more detailed knowledge on this novel syndrome., Design, Setting, and Participants: RTHα was suspected in three index patients from different families. Detailed clinical and biochemical assessment and imaging and genetic analyses were performed in the patients and their relatives. In addition, functional consequences of TRα mutations were investigated in vitro., Results: We studied 22 individuals from three families and identified 10 patients with heterozygous TRα mutations: C380fs387X, R384H, and A263S, respectively. The frame-shift mutation completely inactivated TRα, whereas the missense mutations produced milder defects. These mutations were associated with decreasing severity of the clinical phenotype: the patient in family 1 showed severe defects in growth, mental, and motor development, whereas the seven patients in family 3 had only mild clinical features. The most frequent abnormalities were anemia, constipation, and a delay in at least one of the developmental milestones. Serum free T3 ranged from high-normal to high and serum free T4 and rT3 from normal to low. TSH levels were normal in all patients., Conclusions: This large case series underlines the variation in the clinical phenotype of RTHα patients. RTHα should be suspected in subjects when even mild clinical and laboratory features of hypothyroidism are present along with high/high-normal free T3, low/normal free T4, and normal TSH.

Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty. It is an X-linked recessive disorder resulting from mutations in the androgen receptor (AR) gene. However, AR gene mutations are found in less than a third of PAIS cases. A 16-year-old boy was admitted with complaints of gynecomastia and sparse facial hair. Family history revealed male relatives from maternal side with similar clinical phenotype. His external genitalia were phenotypically male with pubic hair Tanner stage IV, penoscrotal hypospadias, and a bifid scrotum with bilateral atrophic testes. He had elevated gonadotropins with a normal testosterone level. Chromosome analysis revealed a 46,XY karyotype. Due to the family history suggesting a disorder of X-linked trait, PAIS was considered and molecular analysis of AR gene was performed. DNA sequence analysis revealed a novel hemizygous mutation p.T576I (c.1727C>T) in the AR gene. The diagnosis of PAIS is based upon clinical phenotype and laboratory findings and can be confirmed by detection of a defect in the AR gene. An accurate approach including a detailed family history suggesting an X-linked trait is an important clue for a quick diagnosis.

Aim: The current study aimed to investigate the relationship between serum betatrophin levels and metabolic and anthropometric parameters in obese children., Method: The study included 40 obese children with a body mass index (BMI) above 95th centile, and 35 non-obese subjects with a BMI 3-85th centile, whose age and gender were similar to those of the patient group. Fasting serum glucose, insulin, lipid profile, alanine aminotransferase, aspartate aminotransferase, serum betatrophin, and leptin levels were measured to evaluate the metabolic parameters. Total cholesterol:high-density lipoprotein cholesterol and low-density lipoprotein cholesterol:high-density lipoprotein cholesterol ratios were calculated as "atherogenic indices"., Results: Serum betatrophin levels of the obese subjects were significantly lower than that of non-obese subjects (p<0.05). Insulin resistant subjects had significantly lower betatrophin concentrations than those of non-insulin resistant subjects (p<0.05). Betatrophin levels were negatively correlated with the fasting serum insulin and, accordingly insulin resistance index., Conclusion: Serum betatrophin levels are lower in obese and insulin resistant subjects and betatrophin might act as a potential biomarker of insulin resistance in obese children or adolescents., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups., (© 2016 Wiley Periodicals, Inc.)

Background: The aim of this study is to determine the relationship between oxidative stress marker (8-iso-prostaglandine F2α) and glycemic indices computed from daily glucose monitoring data in children with type 1 diabetes mellitus (T1DM)., Methods: Thirty-one children and adolescents with T1DM (median age 12.2 years) and healthy subjects (median age 11.7 years) were enrolled into the study. Anthropometric data were recorded for the entire group before the study. In addition, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c were recorded in T1DM subjects. T1DM subjects performed self-monitoring of blood glucose (SMBG) for a month (at least four times a day) for calculating glycemic indices. Twenty-four-hour urine 8-iso-prostoglandine F2α levels were studied at the end of the study period in the both groups., Results: Median diabetes duration was 5 years, hemoglobin A1c (HbA1c) was 7.3%. Standard deviation (SD) of the blood glucose (BG) was determined as 85 mg/dL. Median urinary 8-iso-prostoglandine F2α was found to be significantly higher than that of the healthy subjects (2808.9 and 298 pg/mg creatinine, p<0.001, respectively). There was no correlation between urinary 8-iso-prostoglandine F2α and age, anthropometric data, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c, or SD of BG in T1DM groups., Conclusions: This study showed that, 8-iso-prostoglandine F2α that is an oxidative stress marker, is significantly higher in T1DM than that of healthy subjects while, no significant relation between glycemic indices and urinary 8-iso-prostoglandine F2α levels were demonstrated. Further studies are needed to assess other factors, and the relationship between glucose fluctuations and oxidative stress markers.

Aim: To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship., Methods: Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses., Results: A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B, HNF1A, PDX1, and BLK mutations in the others. We identified five novel missense mutations - three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic., Conclusion: The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.

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.

Disorders of sex development (DSD) are a generic definition including any problem noted at birth where the genitalia are atypical in relation to the chromosomes or gonads. The most important clinical problems in DSD comprise physical and psychological disturbances and the risk of gonadal tumor development. Germ cell tumor risk is lowest (<5%) in patients with defects in androgene action or synthesis (such as complete androgen insensitivity syndrome, 5α-reductase deficiency), whereas the highest risk (15%-60%) is observed in 46,XY gonadal dysgenesis. The presence of Y chromosomal material in the karyotype increases the risk for the development of gonadal tumors. The reported age of tumor development varies based on the etiology of DSD (gonadal dysgenesis, androgen insensitivity syndrome, androgen synthesis defects, mixed gonadal dysgenesis, etc.). In the past, early gonadectomy was recommended for all cases of 46,XY DSD, however, according to current approaches, gonadal tumor risk is predicted based on the molecular diagnosis and the timing of the gonadectomy depends on the result of molecular analysis. Until now, optimal protocol in the management of DSD is still controversial. In addition to that, safe and well-accepted guidelines are needed. There is limited number of prospective studies on timing of a gonadectomy in childhood and adolescence. Therefore, evidence-based data on timing and indications of gonadectomy in patients with DSD are needed. In this review, recent data regarding gonadal malignancy risk in DSD and recommendations on timing of gonadectomy are presented.

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.

46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.

Objective: Kallmann syndrome (KS) is a genetic disorder with the distinctive features of hyposmia or anosmia and hypogonadotropic hypogonadism. Though hyposmia/anosmia can be evaluated by both objective and subjective smell tests, there is no study comparing these two methods in KS. The aim of the present case series was to discuss the results of objective and subjective smell tests and compare them to volumetric magnetic resonance imaging (MRI)., Methods: A total of six adolescent males (aged between 14-18 years) with KS were examined by objective and subjective olfactometry to test smell function and by specific MRI sequences to measure the olfactory bulbs., Results: The objective smell test showed anosmia in all six of the patients. However, the subjective test revealed anosmia in five patients and hyposmia in one patient. Brain MRI showed olfactory bulb aplasia in all six cases., Conclusion: MRI provides robust evaluation of the olfactory bulb volume. Our data show excellent compatibility between the results obtained via objective olfactometry and those obtained by measuring olfactory bulb volume as determined by MRI and therefore demonstrate that objective olfactometry remains a highly reliable test. Furthermore, although the number of subjects studied was small, these data also suggest that cheaper and more easily available subjective tests could be used in preference to the more expensive as well as labor-intensive and time-consuming objective smell tests. In the event of doubts as to the validity of the subjective tests, the objective olfactometry tests can confirm the diagnosis. The bulb volumetric MRI may be also used in difficult cases.