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We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche. This study included 60 female children with premature pubarche. We retrospectively collected clinical, laboratory, and radiological findings from all participants. We investigated the time interval between pubarche and thelarche in cases wherein premature pubarche was followed by thelarche. The mean age at onset of pubarche was 6.93 ± 0.79 yr old. Among the participants, 16.7% were preterm, 20% were small for gestational age (SGA), and 55% were overweight or obese. The mean time interval between pubarche and thelarche was 11.20 ± 7.41 mo. The mean serum DHEA-S level was higher in the preterm group (p = 0.016), and DHEA-S levels were generally higher in the SGA group (p = 0.004). This study documented the presence of being overweight or obese and having more advanced growth than their genetic potential in half of the patients who had premature pubarche. In addition to these identified risk factors, obesity-independent DHEA-S levels were observed to be higher in patients who had early puberty with the first six months of their follow-up considered to be the most critical time in predicting early puberty.

Introduction Diabulimia is known as an eating disorder specific to individuals with diabetes. Objectives In this study, it was aimed to determine the diabulimia risk and to evaluate the possible relationships between diabulimia risk and diet quality, anthropometric measurements, and biochemical parameters of adolescents with type 1 diabetes. Material and methods In total, 110 adolescents (male: 51.8%, female: 48.2%) with type 1 diabetes between 10–19 years were included in the study. Sociodemographic characteristics and information about diabetes of adolescents were collected using a questionnaire prepared by the researchers through face-to-face interview technique. Anthropometric measurements and 3-day food consumption records were obtained to evaluate their nutritional status, and their biochemical parameters were obtained from hospital files to evaluate their metabolic status. The diet quality was evaluated using the Healthy Eating Index-2015. Diabetes Eating Problem Survey was administered to individuals and it was accepted that diabetics with a total score of ≥ 20 were at risk of diabetes-related eating disorders. Results/Conclusion Among the 110 adolescents included in this study, 31.8% were found to be at risk of diabulimia. There was a significant relationship between the groups with and without diabulimia risk in terms of diet quality scores (P

Parathyroid adenoma is less common than in adulthood, but its morbidity is higher in children. We aimed to evaluate the clinical characteristics of parathyroid adenoma and our clinical experience since the early disease is often asymptomatic and late diagnosed.From 2010 to 2020, all children diagnosed with parathyroid adenoma at our institution were reviewed. We evaluated clinical, biochemical, and radiological aspects and follow-up characteristics.Eight subjects (F/M = 6/2) ranged in age from 10 to 17 years. Three were symptomatic. The symptoms and findings were stomachache (n = 3), myalgia (n = 2), weakness (n = 2), pancreatitis (n = 1), constipation (n = 1), nausea (n = 1), bone ache (n = 1), and anorexia (n = 1). Laboratory findings on admission were as follows: the mean calcium was 12.59 ± 1.28 (11.2-15.3) mg/dL and the mean parathyroid hormone was 244.81 ± 173.61 (74.9-645.4) pg/mL. The most common localization was the lower part of the left parathyroid gland. Parathyroid adenoma could not be demonstrated by ultrasonography in 2 patients. Tc-99m-Sestamibi scintigraphy revealed the presence of parathyroid adenoma in only 7 of 8 patients. All underwent parathyroidectomy. In our follow-up, 2 subjects needed reoperation. A molecular analysis of 6 cases could be done. One was MEN1 positive. RET sequence analysis of 2, and Casr, GNA11, and AP2S1 sequence analysis of 3 were normal.Parathyroid adenoma should be considered in children older than the first decade with hypercalcemia. Suspected cases should undergo both ultrasonography and scintigraphy. Early diagnosis prevents the patients from serious complications of hypercalcemia such as nephrocalcinosis, diabetes insipid, and arrhythmia. It is significant to perform surgery in centers experienced in parathyroidectomy to minimize postoperative complications.

Hyperprolactinaemia refers to increased circulating prolactin and is divided into functional and pathological hyperprolactinaemia. Prolactinoma is the most common cause of severe hyperprolactinaemia. Prolactinomas are rare in children. Treatment outcomes and long-term follow-up data in children are insufficient. Dopamine agonists are the first step in the treatment of prolactinomas. There are no recommendations supported by a high level of evidence regarding the dose and duration of cabergoline treatment.Patients with hyperprolactinaemia were evaluated for etiological, clinical, and follow-up characteristics. The case files of patients with high prolactin levels who were followed up in our clinic between 2001 and 2019 were reviewed retrospectively.27 cases (20 female, 7 male) with hyperprolactinemia were detected. The median age of the cases was 15 years (0.3-17.4). Prolactinoma was detected in 40.7% of the cases (n=11). Among these cases, six were macroadenomas. The median prolactin level was 118 ng/mL (34-4340) in those with prolactinoma and 60 ng/mL (22-200) in the hyperprolactinaemia group (p=0.007). In the prolactinoma group, the median age at presentation in macroadenoma cases (13.8 years) was lower than in microadenoma cases (17 years) (p=0.06). There was a negative correlation between prolactin level and height SDS (r=-0.770, p=0.06). In all cases, the median initial cabergoline dose was 0.5 mg/week, and prolactin levels returned to normal within an average of 2.6±2.4 months. Cabergoline treatment achieved a 50% reduction in adenoma size in the first year of treatment without high doses.Prolactinoma consists of an important group among hyperplolactinemia in children. In our study, prolactinoma was detected in 40.7% of children with hyperplolactinemia, and children with prolonged use (over 4 years) tolerated cabergoline well and prolactin levels normalized without high doses. Follow-up is required for relapse after discontinuing the treatment.

Type 1 pseudohypoaldosteronism (PHA1) is a rare condition characterized by the resistance of the kidney to the effect of aldosterone. Secondary PHA1 is a syndrome that is most often related to urinary tract anomalies (UTAs) and/or urinary tract infections (UTIs). A similar pattern of electrolyte impairment is seen in congenital adrenal hyperplasia (CAH) and secondary PHA1, and CAH is a condition that requires urgent treatment. In our study, eight patients aged between 15 days and 8 months (seven males and one female) were included in the evaluation. It was aimed to evaluate cases of secondary PHA1 in our clinic and to identify the problems encountered in diagnosis and follow-up.The records of the patients who presented to our hospital between February 2010 and 2021 were retrieved and retrospectively scanned.In all cases, hyponatremia, hyperkalemia, hyperaldosteronism, and hyperreninemia were detected. Other biochemical and hormonal tests were normal. Leukocytosis was detected in urine analysis, and urine cultures were productive. UTA was detected in five cases. Nine episodes of PHA1 occurred in eight patients and fungal infections were responsible for causing two episodes. Four episodes of PHA1 needed mineralocorticoid treatment. On the third day, serum electrolytes normalized. Fludrocortisone treatment was continued for 1 week. In one case, UTIs were repeated with PHA1, but in the follow-up, there were no additional problems.Secondary PHA1 should be kept in mind when hyponatremia and hyperkalemia are seen, especially in infants aged under 3 months or older, up to 8 months, who present with non-specific symptoms. Fungal infections should not be forgotten in UTI etiology because PHA1 episodes can be initiated. If CAH is suspected, mineralocorticoid treatment should be rapidly initiated.

In addition to carbohydrate count, this study aims to investigate the impact of the determination of bolus insulin doses by fat and protein counts on postprandial blood glucose level for adolescents having type 1 diabetes mellitus. The study was crossover and randomized; and all of participants were given standard breakfast (insulin dose according to carbohydrate/insulin ratio) for 1 day, and high-fat and high-protein breakfast for 2 days. The insulin dose for one of test meal was determined based on carbohydrate/insulin ratio. In the second application, in addition to carbohydrate/insulin ratios of the adolescents, 1 unit of insulin per what was added for each 200 kcal of energy provided from fat and protein of the meal. Postprandial blood glucose was recorded for 4 h using a continuous glucose monitoring system at intervals of 30 min. The mean blood glucose level between 0 and 240 min following consumption of different meals increased significantly in second application after 150th minute comparing with first application (p 0.05).However, the glycemic excursion of 30–0 min in third application was higher than the excursion in first and second applications while the glycemic excursion in first application between 150 and 120 min was higher than in third application (p

Objective:Ventricular repolarisation changes may lead to sudden cardiac death in obese individuals. We aimed to investigate the relationship between ventricular repolarisation changes, echocardiographic parameters, anthropometric measures, and metabolic syndrome laboratory parameters in obese children.Methods:The study involved 81 obese and 82 normal-weight healthy children with a mean age of 12.3 ± 2.7 years. Anthropometric measurements of participants were evaluated according to nomograms. Obese patients were subdivided into two groups; metabolic syndrome and non-metabolic syndrome obese. Fasting plasma glucose, fasting insulin, and lipid profile were measured. QT/QTc interval, QT/QTc dispersions were measured, and left ventricular systolic and diastolic measurements were performed.Results:Body weight, body mass index, relative body mass index, waist/hip circumference ratio, and systolic and diastolic blood pressures were significantly higher in obese children. QT and QTc dispersions were significantly higher in obese children and also obese children with metabolic syndrome had significantly higher QT and QTc dispersions compared to non-metabolic syndrome obese children (p < 0.001) and normal-weight healthy children (p < 0.001). Waist/hip circumference ratio, body mass index, and relative body mass index were the most important determinant of QT and QTc dispersions. Left ventricular wall thickness (left ventricular posterior wall thickness at end-diastole, left ventricular posterior wall thickness at end-systole, interventricular septal thickness at end-diastole) and left ventricular mass index were significantly higher and ejection fraction was lower in obese children. Left ventricular mass index and interventricular septal thickness at end-diastole were positively correlated with QT and QTc dispersions.Conclusions:Our study demonstrated that QT/ QTc interval prolongation and increase in QT and QTc dispersion on electrocardiogram may be found at an early age in obese children.

Objective: Standard short adrenocorticotropic hormone (ACTH) stimulation test (SST) has traditionally been used for assessing adrenal gland fuction by intravenous (iv) application. However the iv form is not readily available in all countries, including Turkey. The aim of this study was to evaluate the effectiveness of the intramuscular (im) SST. Methods: Patients underwent im SST with suspected adrenal insufficiency (AI) and hyperandrogenism. The SSTs were done with 250 mcg ACTH (Synacthen Depot ampul, concentration 1 mg/mL). The cases were divided into two groups: suspected AI (group 1 n=87); and hyperandrogenism group (group 2 n=124). Definite AI was defined as peak cortisol

The tRNA methyltransferase 10 homologue A (

Objective To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male. Methods A national database was created. The data of patients were asked to be recorded in the data form. Results The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%. Conclusion It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.

Costello syndrome (CS) is a rare member of the group of neuro-cardio-facio-cutaneous diseases known as RASopathies. CS involves characteristic dysmorphic craniofacial features, cardiac defects, and increased cancer susceptibility, depending on the heterozygous activating germline mutations in HRAS. Polyhydramnios and high birth weight are the most common presentations in the perinatal and neonatal periods; while poor postnatal growth, short stature, and failure to thrive are significant issues in infancy. Possible mechanisms of short stature in CS include GH deficiency and feeding difficulties. Only a few reported cases of CS with GH deficiency exist in literature. Here, we describe the 5-yr follow-up of a CS patient with complete GH deficiency treated with recombinant human GH (rhGH) from the age of four years. No significant adverse events regarding progression of hypertrophic cardiomyopathy and tumor development were observed. She has been responsive to treatment with improved growth velocity and height standard deviation scores. She is still under continuous monitoring for concerns on the possible development of cardiac events and malignancies. This case indicated that rhGH therapy is effective for improving the height and growth velocity of CS patients with GH deficiency under close cardiac and oncological monitoring.

Objectives LMNA variants have been previously associated with cardiac abnormalities independent of lipodystrophy. We aimed to assess cardiac impact of familial partial lipodystrophy (FPLD) to understand the role of laminopathy in cardiac manifestations. Study design Retrospective cohort study. Methods Clinical data from 122 patients (age range: 13-77, 101 females) with FPLD were analysed. Mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with an LMNA variant were studied as proof-of-concept for future studies. Results Subjects with LMNA variants had a higher prevalence of overall cardiac events than others. The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants (OR: 3.77, 95% CI: 1.45-9.83). These patients were at higher risk for atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04-32.16). The time to the first arrhythmia was significantly shorter in the LMNA group, with a higher HR of 3.52 (95% CI: 1.34-9.27). Non-codon 482 LMNA variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41-15.98 for arrhythmia; OR: 17.67, 95% CI: 2.45-127.68 for atrial fibrillation or flutter; OR: 5.71, 95% CI: 1.37-23.76 for conduction disease). LMNA mutant hiPSC-CMs showed a higher frequency of spontaneous activity and shorter action potential duration. Functional syncytia of hiPSC-CMs displayed several rhythm alterations such as early afterdepolarizations, spontaneous quiescence and spontaneous tachyarrhythmia, and significantly slower recovery in chronotropic changes induced by isoproterenol exposure. Conclusions Our results highlight the need for vigilant cardiac monitoring in FPLD, especially in patients with LMNA variants who have an increased risk of developing cardiac arrhythmias. in addition, hiPSC-CMs can be studied to understand the basic mechanisms for the arrhythmias in patients with lipodystrophy to understand the impact of specific mutations., NIH Clinical and Translational Science AwardsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [UL1TR000433]; Nutrition Obesity Research Centers [P30 DK089503]; NIH institutional grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK034933]; White Point Foundation of Turkey; Morton S. and Henrietta K. Sellner Professorship in Human Genetics, Infrastructure and data management support has been provided by the NIH Clinical and Translational Science Awards grant UL1TR000433, the Nutrition Obesity Research Centers grant P30 DK089503, and NIH institutional grant DK034933. Finally, the work was supported by generous gifts to the Lipodystrophy Fund at the University of Michigan made by the Sopha family, and the White Point Foundation of Turkey. JWI acknowledges support from the Morton S. and Henrietta K. Sellner Professorship in Human Genetics.

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6\%) female and 92 male cases with a mean age of 8.18 +/- 5.05 years at diagnosis were included. 52.7\% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2\%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6\% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3 +/- 2.1\%, 184.9 +/- 128.9 mg/dL, 9.4 +/- 22.9 IU/L, 1.36 +/- 1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2\%), HNF1A-MODY in 31 (18.3\%), and variants in ABCC8 in 6 (3.6\%), KCNJ11 in 5 (3\%), HNF4A in 2 (1.2\%), and HNF1B in 2 (1.2\%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50\%), while GCK-MODY is the second most frequent (32\%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20\% of cases were diagnosed with HNF1A-MODY.

Objective: The diet quality of adolescents with type 1 diabetes is shaped by some individual factors. These include age, gender, sociodemographic characteristics, lifestyle habits, and adaptation to diabetes treatment. This study aims to investigate the factors affecting the diet quality of adolescents with type 1 diabetes. Material and Methods: The sample in this study consisted of adolescents with type 1 diabetes who were followed in the Department of Pediatric Endocrinology of the Faculty of Medicine at the University of Ankara between July 2017-January 2018. The research data was collected using the face-to-face interview technique with a questionnaire. The physical activity levels of the individuals were determined using a ‘24-hour physical activity level detection form (short)’. Three-day food consumption records were taken and evaluated via BeBiS. The Healthy Eating Index-2010 was used to determine diet quality. Results: The study was conducted with a total of 110 adolescents (M:51.8%; F:48.2%) with type 1 diabetes in the 10-19 age range (mean age:14.0±2.40 years). Only 15.5% of all individuals have good diet quality. In a linear regression model formed by the variables of exercise status, physical activity type, and PAL value of individuals, a positive significant relationship was found between exercise status and diet quality (χ2 (1,n=110)=1.392, p, Amaç: Tip 1 diyabetli adölesanların diyet kalitesi bazı bireysel faktörlere göre değişebilmektedir. Bunlar yaş, cinsiyet, sosyodemografik özellikler, yaşam tarzı alışkanlıkları ve diyabet tedavisine uyumu içerir. Bu çalışmanın amacı, tip 1 diyabetli adölesanların diyet kalitesini etkileyen faktörleri incelemektir. Gereç ve Yöntemler: Bu çalışmanın örneklemini, Temmuz 2017- Ocak 2018 tarihleri arasında Ankara Üniversitesi Tıp Fakültesi Çocuk Endokrinolojisi Anabilim Dalı’nda takip edilen tip 1 diyabetli adolesanlar oluşturmuştur. Araştırma verileri yüz yüze görüşme tekniği kullanılarak toplanmıştır. Bireylerin fiziksel aktivite düzeyleri ‘24 saatlik fiziksel aktivite düzeyi tespit formu (kısa) ‘ile belirlenmiştir. Üç günlük besin tüketim kayıtları alınmış ve BeBis ile değerlendirilmiştir. Diyet kalitesini belirlemek için Sağlıklı Yeme İndeksi-2010 kullanılmıştır. Bulgular: Çalışma, 10-19 yaş aralığında (ortalama: 14,0±2,40 yıl) 57’si erkek (%51,8), 53’ü kadın (%48,2) olmak üzere toplam 110 tip 1 diyabetli adolesan ile gerçekleştirilmiştir. Tüm bireylerin sadece %15,5’i iyi diyet kalitesine sahipti. Diyet kalitesinin cinsiyete göre dağılımı istatistiksel olarak anlamlı değildi. (p>0,05). Bireylerin egzersiz durumu, fiziksel aktivite türü ve PAL değeri değişkenlerinden oluşan doğrusal regresyon modelinde egzersiz durumu ile diyet kalitesi arasında pozitif yönde anlamlı bir ilişki bulunmuştur (χ2 (1,n=110)=1,392, p

Background: Large contiguous gene deletions at the distal end of the short arm of chromosome 9 result in the complex multi-organ condition chromosome 9p deletion syndrome. A range of clinical features can result from these deletions with the most common being facial dysmorphisms and neurological impairment. Congenital hyperinsulinism is a rarely reported feature of the syndrome with the genetic mechanism for the dysregulated insulin secretion being unknown. Methods: We studied the clinical and genetic characteristics of 12 individuals with chromosome 9p deletions who had a history of neonatal hypoglycaemia. Using off-target reads generated from targeted next-generation sequencing of the genes known to cause hyperinsulinaemic hypoglycaemia (n=9), or microarray analysis (n=3), we mapped the minimal shared deleted region on chromosome 9 in this cohort. Targeted sequencing was performed in three patients to search for a recessive mutation unmasked by the deletion. Results: In 10/12 patients with hypoglycaemia, hyperinsulinism was confirmed biochemically. A range of extra-pancreatic features were also reported in these patients consistent with the diagnosis of the Chromosome 9p deletion syndrome. The minimal deleted region was mapped to 7.2 Mb, encompassing 38 protein-coding genes. In silico analysis of these genes highlighted SMARCA2 and RFX3 as potential candidates for the hypoglycaemia. Targeted sequencing performed on three of the patients did not identify a second disease-causing variant within the minimal deleted region. Conclusions: This study identifies 9p deletions as an important cause of hyperinsulinaemic hypoglycaemia and increases the number of cases reported with 9p deletions and hypoglycaemia to 15 making this a more common feature of the syndrome than previously appreciated. Whilst the precise genetic mechanism of the dysregulated insulin secretion could not be determined in these patients, mapping the deletion breakpoints highlighted potential candidate genes for hypoglycaemia within the deleted region.

Background Pathogenic variants in Lamin A/C (LMNA) gene are the most common monogenic etiology in Familial Partial Lipodystrophy (FPLD) causing FPLD2. LMNA pathogenic variants have been previously associated with cardiomyopathy, familial arrhythmias or conduction system abnormalities independent of lipodystrophy. We aimed to assess cardiac impacts of FPLD, and to explore the extent of overlap between cardiolaminopathies and FPLD. Methods We conducted a retrospective review of an established cohort of 122 patients (age range: 13-77, M/F 21/101) with FPLD from Michigan (n = 83) and Turkey (n = 39) with an accessible cardiac evaluation. Also, functional syncytia of mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a FLPD2 patient was studied for assessment of autonomous rhythm and action potential duration with optical mapping using a voltage sensitive dye. Results In the whole study cohort, 95 (78%) patients had cardiac alterations (25% ischemic heart disease, 36% arrhythmia, 16% conduction abnormality, 20% prolonged QT interval, 11% cardiomyopathy, and 15% congestive heart failure). The likelihood of having an arrhythmia (OR; 3.95, 95% CI: 1.49-10.49) and conduction disease (OR: 3.324, 95% CI: 1.33-8.31) was significantly higher in patients with LMNA pathogenic variants. Patients with LMNA pathogenic variants were at high risk for atrial fibrillation/flutter (OR: 6.77, 95% CI: 1.27- 39.18). The time to first arrhythmia was significantly shorter in the LMNA group with a higher hazard rate of 3.04 (95% CI: 1.29-7.17, p = 0.032). Non-482 LMNA pathogenic variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41- 15.98 for arrhythmia; OR: 17.67, 95% CI: 2.44- 127.68 for atrial fibrillation/flutter; OR: 5.71, 95% CI: 1.37- 23.76 for conduction disease. hiPSC-CMs from a FPLD2 patient had higher frequency of autonomous activity, and shorter Fridericia corrected action potential duration at 80% repolarization compared to control cardiomyocytes. Furthermore, FPLD2 functional syncytia of mature hiPSC-CMs presented several rhythm alterations such as early after-depolarizations, spontaneous quiescence and spontaneous tachyarrhythmia; none of those were observed in the control cell lines. Finally, FPLD2 hiPSC-CMs presented significantly slower recovery in chronotropic changes induced by isoproterenol exposure; which indicates disrupted beta-adrenergic response. Conclusion Our results suggest the need for vigilant cardiac monitoring in FPLD, especially in patients with FPLD2 who have an increased risk to develop cardiac arrhythmias and conduction system diseases. In addition, study of human induced pluripotent stem cell-derived cardiomyocytes may prove useful to understand the mechanism of cardiac disease and arrhythmias and to create precision therapy opportunities in the future.

Amaç: Esnek insülin tedavisi, öğünlerin zamanı, yiyecek seçimi ve öğünlerdeki insülin dozunun karbonhidrat sayımı yaparak kişinin yaşam tarzına göre ayarlandığı yoğun insülin tedavisidir. Çalışmamızın amacı tip 1 diyabetli çocuklarda esnek insülin tedavisinin metabolik kontrole, antropometrik özelliklere ve sağlık parametrelerine etkilerinin incelenmesi ve tedaviye uyumun değerlendirilmesidir. Gereç ve Yöntemler: Esnek insülin tedavisini balayı dönemi sonrası en az 2 yıl süre kullanan tip 1 diyabetli 39 hastanın, dosya verileri retrospektif olarak incelendi. İki yıllık izlemde ortalama HbA1c düzeyi >%7.5 olan hastalar grup 1, ≤%7.5 olan hastalar grup 2 olarak tanımlandı. Her grubun 2 yıllık seyri değerlendirildi, gruplar karşılaştırıldı.Bulgular: Hastaların ortanca diyabet süresi 52 (25-152) aydı. Grup 1’de 23 (%59) hasta, grup 2’de 16 (%41) hasta mevcuttu. Gruplar arasında diyabet süresi benzerdi(p>0.05). Grup 2’deki olguların, başlangıç HbA1c düzeyleri daha yüksekti (9.3 vs 11.6, p=0.046). Her iki grubun da tedavinin 1. yılında HbA1c düzeyinin azaldığı (p0.05). Her 2 gruptaki olgular da genetiği içinde büyüyen ve yıllık uzamaları normal olan olgulardı. Esnek tedavi alan tüm hastalar değerlendirildiğinde izlemin 2. yılında, ortalama insülin dozlarının arttığı saptandı (p=0). Grup 2’deki hastalar diyetine uyan (p=0.038), karbonhidrat sayımı yapan (p=0.025) ve daha az hazır yemek tüketen (p=0.018) hastalardı.Gruplar arasında ciddi hipoglisemi ve diyabetik ketoasidoz sıklığı benzerdi(p>0.05). Grup 1’deki trigliserid, total kolesterol, LDL, VLDL düzeyleri grup 2’den yüksek, HDL düzeyi düşük olmasına rağmen, fark saptanmadı (p>0.05). Dislipidemi gelişen hastaların ortanca diyabet süresi, dislipidemi gelişmeyen hastalardan daha uzundu(p=0.018). Sonuç: Esnek insülin tedavisi, sağlıklı beslenen ve etkili karbonhidrat sayımı yapan çocuklarda, %VKİ’inde anormal artış yapmadan HbA1c düzeyini ≤%7.5 düşürebilir., Objective: Flexible insulin therapy is intensive insulin therapy where the time of meals, food selection, and the dose of insulin in meals are adjusted to the patient’s lifestyle by carbohydrate counting. The aim of our study is to investigate the effects of flexible insulin treatment on metabolic control, anthropometric properties and health parameters in children with type 1 diabetes and to evaluate compliance with treatment.Material and Methods: Medical records of 39 children who used flexible insulin treatment at least 2 years after honeymoon period were retrospectively evaluated. Patients were grouped according to mean HbA1c as group 1 (HbA1c >7.5%) and group 2 (0.05). Group 2 had higher initial HbA1c levels (9.3 vs 11.6, p=0.046). HbA1c levels of both groups were decreased at first year (p0.05). All patients had normal growth according to their genetic potential. Mean insulin dose of patients was increased in second year (p=0). Compliance of diet (p=0.038), carbohydrate count (p=0.025) and less fast food consumption(p=0.018) were more common in group 2. Conclusion: The frequency of severe hypoglycemia and diabetic ketoacidos were similar (p>0.05). Group 1 had higher triglyceride, total cholesterol, LDL, VLDL and lower HDL levels but not statistically significant (p>0.05). Patients with dyslipidemia had longer median diabetes duration than without dyslipidemia (p=0.018).

Hypochondroplasia is a cause of disproportionate short stature and characterized by minor clinical manifestations. The aim of this study was to evaluate the efficacy of long-term growth hormone (GH) therapy in hypochondroplastic cases with inadequate response to GH stimulation tests. In this study, six patients who had a height standard deviation score of -3.43 before the treatment and a mean age of 7.42 years and who had received GH treatment at a dose of 0.2 mg/kg/week for a mean period of 4.45 years were evaluated. A good response was found in the first year of treatment, but this increase was not found to be sufficient for the patients to achieve an adequate final height.

Eren, Erdal/0000-0002-1684-1053; Abaci, Ayhan/0000-0002-1812-0321; sahin, nursel muratoglu/0000-0002-8215-0146; siklar, zeynep/0000-0003-0921-2694; berberoglu, merih/0000-0003-3102-0242; Mengen, Eda/0000-0003-1597-8418 WOS: 000463248300011 PubMed: 30132287 BackgroundStudies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5-RD2) are limited and they were conducted on small number of patients.ObjectiveTo present genotype-phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5-RD2.Materials and methodsPatients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated.ResultsA total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were8.5 for minipuberty,10 for prepuberty, and17 for puberty.ConclusionThere is no significant genotype-phenotype correlation in 5-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status. Turkish Pediatric Endocrinology and Diabetes Society [032015] This work was supported financially by the Turkish Pediatric Endocrinology and Diabetes Society (Grant number: 032015).

Study Objective Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and chronic anovulation, which affects 5%-10% of reproductive-age women. Diagnosis of adult patients with PCOS is made easily with clinical and laboratory methods and the anti-Mullerian hormone (AMH) level are accepted as a good indicator. However, there is still no complete consensus on the diagnosis of PCOS in adolescents. Design and Setting Prospective cohort study, December 2013 to November 2014. Participants The study was conducted on adolescent girls with oligomenorrhea, with at least 2 years since menarche. The study group consisted of adolescent girls with complete PCOS and incomplete PCOS. A control group was formed of healthy adolescent girls. Complete PCOS was diagnosed according to the Rotterdam criteria, as the presence of all the following characteristics: oligomenorrhea, hyperandrogenism, and polycystic ovarian morphology on ultrasound image. Incomplete PCOS was accepted as “oligomenorrhea and polycystic ovarian morphology,” or “oligomenorrhea and hyperandrogenism.” Interventions and Main Outcome Measures All patients underwent a physical examination and the anthropometric assessments, insulin resistance, and acanthosis nigricans were recorded. It was also noted whether or not the patient had an acne score. The Ferriman-Gallwey score was applied to evaluate hirsutism. Results The results of this study showed that no statistically significant difference was found between the PCOS and incomplete PCOS groups and the control group with respect to AMH levels. Conclusion The use of adult-specific diagnostic methods in adolescence might result in an incomplete diagnosis and inadequate treatment plan. Although the serum AMH level clearly facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in PCOS diagnosis is still controversial and further studies are needed.

Objectives: Continuation of growth hormone (GH) treatment in adolescents with severe childhood onset idiopathic GH deficiency (IGHD) during the transition period, irrespective of achievement of final height, is still debatable. We aimed to prospectively investigate the metabolic profile, bone mineral density (BMD) and body composition of patients with IGHD in whom GH treatments were terminated after they had reached their final height, six months after the cessation of therapy. Methods: Twelve patients, six of whom had peak GH levels 5 ng/mL (transient GHD, group 2) after insulin stimulation test were evaluated for anthropometric and laboratory parameters including fasting blood glucose (FBG), fasting insulin, lipid profile, BMD, body composition measurements and 24-hour ambulatory blood pressure monitoring before (baseline) and at six months after discontinuation of GH. Results: No differences were found in clinical, laboratory, BMD and body composition measures between groups 1 and 2 at baseline. All IGHD patients had significant increments of body weight (BW), body mass index (BMI), BMD, total body fat (TBF), TBF%, truncal fat (TF) and TF% after GH cessation. Six months later BW, BMI, BMD and TF% was increased significantly while FBG and lipids showed no change in group 1. In group 2, TBF% and TF% were increased, FBG, total cholesterol and high-density lipoprotein decreased after six months. Changes in these parameters in group 2 were not statistically different from group1. Conclusion: TF% increase in both groups after cessation of therapy. We did not observe a clinical condition requiring GH treatment in any of the study subjects during the follow-up period.

Objective: In studies on the relationship between amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) concentration and height velocity in children, CNP has been implicated as an emerging new growth marker during childhood. It has been reported that besides its well-studied role in growth, plasma CNP levels are reduced in overweight and/or obese adolescents, suggesting CNP as a potential biomarker in childhood obesity. The primary goal of this study was to test this hypothesis in a Turkish population. Methods: Consent was taken from 317 children [ages 0-18 (158 girls, 159 boys)] and their parents. All subjects were physically examined; anthropometric measurements were obtained. Body mass index was calculated. During routine blood work, 1 mL extra blood was taken. Plasma NT-proCNP concentration was measured by enzyme-linked immunosorbent assay. Results: Results confirmed the previously described relationship between plasma NT-proCNP concentration and growth velocity. Plasma NT-proCNP concentration showed a negative correlation with age, weight, and height in children. Gender was not a factor that alters the age-dependent plasma NT-proCNP concentration until puberty. Conclusion: Unlike previous reports, plasma NT-proCNP concentration of overweight/obese children was not significantly lower than that of children with normal weight in age groups analyzed in a Turkish population. Thus, it is too early to conclude that CNP is a potential biomarker in childhood obesity. Further studies are necessary to address this question. © 2017 by Turkish Pediatric Endocrinology and Diabetes Society.

Objective This study aimed to call attention to hypercalcemia, a rare finding in children which carries the potential of leading to serious complications without proper intervention. Methods Diagnosis, treatment, and clinical course of children with sustained hypercalcemia admitted between the years 2006-2016 were reviewed. Group 1 [parathyroid hormone (PTH)-dependent] consisted of patients with high/unsuppressed PTH levels and group 2 (PTH-independent) included cases with normal/suppressed PTH levels. Results Twenty patients (11 male, 9 female) with a median age of 6.25 (0.03-17.88) years were evaluated. Symptoms were mostly related with the gastrointestinal system, while six patients (30%) were asymptomatic. Physical examination findings were diverse, non-specific, and normal in four patients (20%). Median time of diagnosis was 45 (2-720) days. Patients were divided into group 1 (n=7) and group 2 (n=13). Most frequent etiologies were primary hyperparathyroidism (n=5), idiopathic infantile hypercalcemia (IIH) (n=5), and malignancy (n=4). A moderate positive correlation was noted between serum calcium and creatinine levels (r=0.53, p=0.02). Nephrocalcinosis was the most common complication (n=9) (45%). Treatment was not implemented in 2 patients with mild hypercalcemia, while other patients received medical treatment ± surgery. Treatment-resistant patients were cases of malignancies and neonatal severe hyperparathyroidism. Long-term follow-up displayed resistant hypercalciuria in three infants diagnosed as IIH. Conclusion Many patients with childhood hypercalcemia are asymptomatic or exhibit a non-specific and heterogeneous clinical presentation, resulting in delayed diagnosis. Mild cases may not be recognized, while symptoms may be missed in the presence of accompanying illnesses. Nevertheless, serious complications may only be avoided with prompt diagnosis and intervention.

Peutz-Jeghers syndrome (PJS) is inherited as an autosomal dominant trait characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation, and an increased risk of neoplasm. Large-cell calcifying Sertoli cell tumor (LCCSCT) is a kind of sex cord-stromal tumor which may co-exist with PJS and which is characterized radiologically by calcification foci within the testes. Surgical treatment options for this tumor range from testis-preserving surgery to radical orchiectomy. Not with standing this invasive approach, recently, there are some case reports demonstrating the efficacy of aromatase inhibitors in avoiding orchiectomy and its associated complications. In this paper, we have presented a LCCSCT case diagnosed in a boy with PJS and his response to anastrozole treatment.

Çalışmada 24 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. 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, 1st, 2nd and 3rd 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 1st and 2nd 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 3rd year Pill 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.

Malnutrition and growth retardation (GR) are major extraintestinal presentations of inflammatory bowel disease (IBD) in childhood and are especially prevalent among those with Crohn's disease (CD). We aimed to evaluate nutritional and growth status and body composition (BC) of children with IBD during a 1-year follow-up.Thirty-eight children with IBD and 57 age- and sex-matched controls were recruited prospectively. Anthropometry (weight, height, body mass index (BMI), and triceps skinfold thickness (TSFT) indicated as z scores for age and sex and mid-arm circumference) and bioelectrical impedance analysis were performed at baseline (T0) and after 1 year (T1). Disease activity was evaluated by clinical scoring systems. GR was defined as HAZ -2, undernutrition as WAZ -2, severe malnutrition (SM) as BMIZ -2, and obesity was defined as BMIZ +2. A p value of0.05 was considered statistically significant.Thirty-six children with IBD (22 ulcerative colitis, 12 CD, and 2 indeterminate colitis) and 43 controls completed the study. Most patients were in remission during the study period (T0:71.4%; T1:72.2%). No significant differences were found regarding the frequency of GR (5.6%/8.3%), undernutrition (11.1%/2.8%), and SM (11.1%/5.6%) between T0 and T1 in the IBD group. The changes in anthropometrics and BC measurements during the study period did not differ between the groups except for the TSFT z score.Most patients with IBD were well nourished and grown, although some children were underweight and had GR. Our results suggest that, in IBD patients, the fat mass (FM) showed a gradual increase over time compared with controls.

International audience; Isolated growth hormone deficiency (IGHD) is a rare condition mainly caused by mutations in GH1. The aim of this study was to assess the contribution of GHRHR mutations to IGHD in an unusually large group of patients. All GHRHR coding exons and flanking intronic regions were sequenced in 312 unrelated patients with nonsyndromic IGHD. Functional consequences of all newly identified missense variants were assessed in vitro (i.e., study of the expression of recombinant GHRHRs and their ability to activate the cyclic adenosine monophosphate (cAMP) signaling pathway). Genotype-phenotype correlation analyses were performed according to the nature of the identified mutation. We identified 20 different disease-causing GHRHR mutations (truncating and missense loss-of-function mutations), among which 15 are novel, in 24 unrelated patients. Of note, about half (13/24) of those patients represent sporadic cases. The clinical phenotype of patients with at least one missense GHRHR mutation was found to be indistinguishable from that of patients with bi-allelic truncating mutations. This study, which unveils disease-causing GHRHR mutations in 8% (24/312) of IGHD cases, identifies GHRHR as the second IGHD gene most frequently involved after GH1. The finding that 8% of IGHD cases without GH1 mutations are explained by GHRHR molecular defects (including missense mutations), together with the high proportion of sporadic cases among those patients, has important implications for genetic counseling.