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Background: Osteogenesis imperfecta (OI), is a heritable, heterogeneous connective tissue disorder, characterized by fragile bones. There are conflicting results about genotype-phenotype correlations and efficiency of bisphosphonate treatment in this disorder. Aim: We aimed to evaluate the clinical, genetic characteristics, and long-term follow-up results of children and adolescents with OI. Materials and methods: A two-center retrospective study was conducted using demographic, clinical, and genetic data obtained from the medical records of the patients. Results: Twenty-nine patients (62% male, median age; 3.6 years) with OI diagnosis from 26 families were included in the study. Thirteen different variants (nine were novel) were described in 16 patients in COL1A1, COL1A2, and P3H1 genes. Our siblings with homozygous P3H1 variants had a severe phenotype with intrauterine and neonatal fractures. Twenty-two patients were treated with bisphosphonates (17 of them with pamidronate, five with alendronate) with a median duration of 3.0 (1.6-4.8) years. Eleven patients (50%) suffered from fractures after the treatment. Haploinsufficiency variants in COL1A1 caused a milder skeletal phenotype with less fracture count and better treatment outcomes than structural variants. When compared with the anthropometric measurements at the initial diagnosis time, height Z-scores were lower on the last clinical follow-up (p = 0.009). Conclusions: We could not find an obvious genotype-phenotype correlation in Turkish OI patients with COL1A1 or COL1A2 variants. Treatment with pamidronate was effective in reducing fracture counts, without any long-term adverse effects.

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.

Objectives Variants in fibroblast growth factor receptor-1 (FGFR1) may either cause isolated hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS). Although the relationship of genes classically involved in IHH with combined pituitary hormone deficiency (CPHD) is well established, variants in FGFR1 have been presented as a rare cause of this phenotype recently. Case presentation Herein, we report an adopted 16-year-old male presented with delayed puberty and micropenis. He had undergone surgery for bilateral undescended testes in childhood. He was normosmic, and the pituitary imaging was normal. However, hypogonadotropic hypogonadism and growth hormone deficiency were detected, associated with a heterozygous nonsense variant (c.1864 C>T, p.R622X) in FGFR1. Conclusions FGFR1 variants are among the causes of IHH and KS, which are inherited in an autosomal dominant manner and can be associated with midline defects. It should also be kept in mind that CPHD may be associated with FGFR1 variants in a subject with normal olfactory function.

Adrenal yetmezlik olgulari, hayati tehdit eden sok ile karakterize adrenal kriz tablosu ile karsimiza cikabilecegi gibi ozgun olmayan belirtilerle de basvurabilir. Hastalarin, mortalite ve morbiditesi yuksek olan adrenal kriz tablosu oncesinde taninip tedavi edilmesi hayati oneme sahiptir. Bu makale ile Hashimoto tiroditi nedeniyle izlemde iken asiri kilo kaybi, halsizlik, cilt renginde koyulasma bulgulari gelisen ve Addison Hastaligi tanisi alan 16 yasindaki kiz olgu uzerinden cocukluk yas grubunda adrenal yetmezlik tablosunun vurgulanmasi amaclanmistir.

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 _10.0 ng/mL or androstenedione _ 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.

There are numerous causes, such as environmental factors, medications, endocrine disorders, and genetic factors, that can lead to obesity. However, severe early-onset obesity with abnormal feeding behavior, mental retardation, dysmorphic features, organ-specific developmental abnormalities, and endocrine disorders suggest a genetic etiology. Mutations in genes related to the leptin-melanocortin pathway play a key role in genetic obesity. This pathway controls hypothalamic regulation of food intake. A few cases have been reported to have mutations in leptin (LEP) or leptin receptor (LEPR) genes. The cases had severe early-onset obesity, hyperphagia, and additional features, such as altered immune function, hypogonadism, and hypothyroidism. We present a 3-year-old male patient with severe early-onset obesity whose genetic analysis revealed a homozygous, novel, and pathogenic variant (c.1603+2T>C) in LEPR.

Background Hypoglycemia is the most common and severe complication of insulin treatment during the management of type 1 diabetes mellitus (T1DM). Despite its importance, there is a lack of data about the efficacy and superiority of the carbohydrate sources used in hypoglycemia management in children and adolescents. Objective We aimed to compare the effectiveness of honey, fruit juice, and sugar cubes as simple carbohydrates used in the primary treatment of hypoglycemia in children and adolescents with T1DM, who attended a diabetes summer camp. Methods A prospective randomized study was performed in a 5-days-long diabetes summer camp. Three different types of simple carbohydrates; sugar cubes, honey, or fruit juice were randomly given for the treatment of hypoglycemia and the recovery results in the three groups were compared. Results About 32 patients (53.1% male, mean age 12.9 ± 1.9 years) were included and 158 mild hypoglycemic episodes were observed. Sugar cubes, honey, and fruit juice were given in 46 (29.1%), 60 (37.9%), and 52 (33%) events, respectively. We found that honey and fruit juice had similar efficiency in recovering hypoglycemia in 15 minutes with a rate of 95% and 98%, respectively. However, sugar cubes had a significantly lower impact on treatment of hypoglycemia than the others, with a recovery rate of 84.7% at 15 minutes. Conclusions This study showed, for the first time, that honey and fruit juice were more effective in treating hypoglycemia than sugar cubes, and can be preferred in treating hypoglycemic events in children and adolescents with T1DM.

WOS: 000429850300010, Pheochromocytoma is a rare disease that is characterized by the increased production and secretion of catecholamines from the adrenal medulla. The disease is autosomal dominant, and frequently sporadic and unilateral. Pheochromocytoma, which is diagnosed during childhood, mostly arises as a part of cancer susceptibility syndromes. Among these syndromes, von-Hippel Lindau (VHL) syndrome is dominantly inherited, and is frequently identified in childhood pheochromocytoma. VHL syndrome is clinically characterized with hemangioblastomas of the central nervous system and retina, renal cell carcinoma, and pheochromocytoma, and has been demonstrated to have a strong genotype-phenotype correlation. In this case report, we presented an 11-year-old male who was found to have early-onset isolated bilateral pheochromocytoma and V84L mutation in VHL. We aimed to emphasize that this rarely reported mutation is associated with VHL Type 2C that classically manifests with early-onset isolated bilateral pheochromocytoma.

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) >95th 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 (p0.05). 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.

Background. Aromatase deficiency leading to virilization in mother and female fetuses during pregnancy is a rare disease. It is characterized by impaired estrogen production, increased gonadotropins, and ovarian cysts. Case. Herein, we report a clinical phenotype of the virilized female due to a novel compound heterozygous variant in CYP19A1 [IVS10 + 1 G> A; c.344 G> A (p.R115Q)], with normal gonadotropin levels at the time of admission and histologically normal ovarian tissues. Conclusion. Aromatase deficiency should also be considered even if the initial follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels are normal, and ovarian cysts are lacking. © 2020, Turkish National Pediatric Society. All rights reserved.

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.

Objective Studies examining changes in thyroid function in the course of chronic liver disease have mostly been conducted in adults. The aim of this study was to investigate thyroid dysfunction in children with chronic liver diseases. Methods Between 2005 and 2018, patients aged up to 18 years of age, diagnosed with chronic liver disease and had thyroid function test results available were included. Anthropometric characteristics, liver and thyroid function results were collected and analyzed. Results The study included 107 (53 female; 49.5%) patients aged between one month and 18 years-old. Of the 107 patients, 96 (89.7%) had normal thyroid function results, seven (6.5%) had subclinical hypothyroidism (SH) and four (3.7%) had euthyroid sick syndrome. Of the patients with SH, one (14.2%) had glycogen storage diasease, one (14.2%) had biliary atresia, one (14.2%) had undiagnosed cholestatic liver disease, one (14.2%) had Alagille syndrome, one (14.2%) had idiopatic hepatitis, one (14.2%) had progressive familial intra-hepatic cholestasis and one (14.2%) had congenital hepatic fibrosis. Spearman correlation analysis showed a negative correlation between free tri-iodothyronine and direct bilirubin (r=-0.329, p=0.027). Conclusion In conclusion, euthyroid sick syndrome or SH may affect up to 10% of children with chronic liver diseases. It is suggested that thyroid function should be evaluated in cases of pediatric chronic liver disease at diagnosis and during follow-up. Moreover, this study is the first to show a negative correlation between free T3 levels and direct bilirubin, suggesting a possible association between liver disease severity and thyroid function.

AimThe present study aimed to evaluate systolic and diastolic myocardial function in children and adolescents with congenital adrenal hyperplasia.MethodsThe 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 (>10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging.ResultsPatients 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 (pConclusionThis 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.

This study aimed to investigate the relationship between serum irisin level and metabolic and anthropometric parameters in obese children.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.Serum irisin and leptin levels of the obese children were significantly higher than those of the healthy children [median irisin levels, 141.2107.6ng/mL, p=0.024; median leptin levels, 10.92.9pg/mL, P0.001, 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.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.

Intratubular large cell hyalinizing Sertoli cell neoplasia (ITLCHSCN) resulting from Sertoli cells of the testis are mainly reported in young adults and these are rarely seen in childhood. The most common presenting symptoms of the patients diagnosed with ITLCHSCN are gynecomastia, enlargement in the testicles, increase in growth velocity, and advanced bone age. Symptoms are basically resulting from increased aromatase enzyme activity in Sertoli cells. In this case report, an eight-and-a-half-year-old case presenting with complaint of bilateral gynecomastia since two years, showing no endocrine abnormality in laboratory during two years of follow-up, determined to have progression in bilateral gynecomastia, increase in testicular volumes, advanced bone age, increase in growth velocity in the clinical follow-up, and diagnosed with ITLCHSCN after testis biopsy was presented.

Introduction: Several case reports stress that high-dose biotin causes incorrect laboratory results. However, the extent of this interference in children is not systematically studied. Aim: To assess factors associated with biotin interference on thyroid function tests in subjects with biotinidase deficiency. Method: The study included 44 children who were treated with oral biotin (Group 1, median dose: 10 mg/day [25–75p; 10–10], age: 1.83 years [1.04–2.90]) and 30 healthy subjects (Group 2, age: 1.05 years [0.37–3.37]). Thyroid function tests were performed with two different assays, and streptavidin-coated particles were used in order to remove biotin from serum samples of cases with biotin interference. Results: The measurements were first performed with Beckman Coulter. In Group 1, remarkably high levels of fT3 and fT4 were found in 26 (59.1%) and 25 (56.8%) patients, respectively. Thyroid hormone functions were all normal in Group 2. Significantly higher serum biotin levels were detected in interference-positive children (p < 0.001). The serum biotin levels in Group 1 showed a strong positive correlation with fT3 (r = 0.867, p < 0.001) and fT4 levels (r = 0.905, p < 0.001). A serum biotin level of 80.35 µg/L was found to be the best cut-off value for predicting interference (sensitivity: 96.2% and specificity: 94.4%). When analyzed with Siemens Advia Centaur XP, all thyroid function tests were normal in both groups except in one patient (2.27%) with slightly elevated fT3 level in Group 1. Repeated tests with Beckman Coulter after neutralization of biotin with streptavidin magnetic particles in serum samples of the interference-positive cases revealed normal thyroid hormone levels. Conclusion: Interference is an important problem in thyroid function tests in nearly 60% of all children receiving biotin treatment for biotinidase deficiency. Serum levels of biotin rather than the dosage are the main determinant of interference, which can be eliminated by choosing appropriate laboratory methods.

Objective: The use of alendronate, one of the bisphosphonates that can be used orally in the treatment of osteoporosis, has become widespread in recent years. In this study, we aimed to compare the efficacy of these two different treatment regimens such as weekly and daily oral alendronate in patients with secondary osteoporosis.

Ozet Infantil hemanjiyom erken cocukluk doneminde sik gorulen benign vaskuler bir tumordur. Tipik olarak kucuk bir lezyon olarak baslar, ilk dokuz ayda hizla buyur ve yillar icinde geriler. Infantil hemanjiyom vakalarinin yaklasik %20’si kanama, ulserasyon ve obstruksiyon nedeniyle tedavi gerektirir. Bir beta bloker olan propranolol gunumuzde infantil hemanjiyom tedavisinde ilk secenektir. Buyumeyi engellemek icin olabildigince erken baslanmasi, lezyonun tekrar etme riskini azaltmak icin de en az bir yil sureyle kullanilmasi gerekmektedir. Propranalol, etkin ve guvenilir bir tedavi olmakla birlikte, hipoglisemi ve buna bagli konvulziyon, bradikardi, hipotansiyon, atriyoventrikuler blok ve bronkospazm gibi ciddi yan etkilere neden olabilir. Bu makalede, hemanjiyoma yonelik propranolol tedavisi altinda iken ciddi hipoglisemi gelisen 18 aylik (bir kiz) olgunun klinik ozellikleri sunulmustur. Summary Infantile hemangioma is common benign vascular tumor in early childhood. It typically appears as a small lesion, grows rapidly during the first nine months of life, and resolves over years. Approximately 20% of cases with infantile hemangioma require treatment due to bleeding, ulceration, and obstruction. Propranolol, a beta-blocker, is the first-choice treatment for infantile hemangioma. It must be started as soon as possible to prevent growth and must be used for at least one year to reduce the risk of recurrence of the lesion. Propranolol is an effective and safe treatment, however, it may cause severe side effects such as hypoglycemia and associated convulsion, bradycardia, hypotension, atrioventricular block, and bronchospasm. In this report, we present the clinical features of an 18-month-old female infant with severe hypoglycemia under propranolol therapy for hemangioma.

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes, with autosomal-dominant inheritance, which usually develops before 25 years of age. MODY is classically caused by a heterozygous mutation of genes known to affect insulin production or secretion. Heterozygous inactivating hepatocyte nuclear factor 4A (HNF4A) mutations, one of the rare subtypes of MODY, cause impaired insulin secretion and subsequent glucose intolerance especially in adolescence. Conversely, HNF4A mutations are also known to be associated with macrosomia and hyperinsulinemic hypoglycemia in newborns. Herein, we report a rare cause of diabetes resulting from a novel heterozygous mutation in the HNF4A gene. In conclusion, genetic testing should be considered in order to establish an accurate diagnosis and provide an opinion in determining the appropriate type of treatment.

The aims of the present study are to evaluate the effect of l-dopa on the secretion of cortisol and adrenocorticotropic hormone (ACTH) in short children and compare the performance of this test with the insulin tolerance test (ITT) in a large number of patients. A total of 29 short but otherwise healthy children [mean age 9.5 ± 3.1 years (range 3.7–14.9 years)] who had inadequate growth hormone (GH) responses to ITT, which was performed as the first test, were consecutively enrolled in this study. GH, cortisol, and ACTH levels were measured just before administration of l-dopa and then at 30-min intervals afterward over a total time of 120 min. Peak concentrations of cortisol and ACTH exceeding 18 µg/dL (496 mmol/L) and 46 pg/mL (10.2 pmol/L), respectively, were defined as an adequate response. While the l-dopa test revealed that 26 of the 29 children (89.7%) had peak serum cortisol levels of > 18 µg/dL, the ITT revealed that only 23 children (79.3%) had adequate cortisol responses. The l-dopa test revealed normal ACTH responses (> 46 pg/mL) in 24 (82.8%) patients. Peak cortisol levels were higher in children with normal ACTH responses than in those with subnormal ACTH responses (25.6 ± 6.2 vs. 19.5 ± 6.4 µg/dL, p = 0.054), but the difference observed was statistically insignificant. The results of the current study confirm that the l-dopa test is a reliable test of cortisol secretion. As such, this test may be applicable to assessments of the hypothalamic–pituitary–adrenal axis.

Amaç: Kistik fibrozis progresif akciğer hasarı, kronik solunum yolu enfeksiyonları, büyüme geriliği ve erken ölüme neden olan sindirim ve solunum disfonksiyonu ile karakterize multistemik, hayatı kısıtlayan, otozomal resesif genetik bir hastalıktır. Kistik fibrozis ekzokrin panreatik yetmezlik, büyüme geriliği, kemik hastalıkları, hipogonodism ve tiroid hastalıklarını kapsayan bazı önemli endokrin anormalliklere neden olabilmektedir. Bu çalışmada amaç, kistik fibrozisli çocuklarda tiroid disfonksiyonu prevelansını araştırmak ve bu hastaların genel karakteristiklerini belirlemektir.Gereç ve Yöntemler: Çalışma, Ocak 2015-Haziran 2015 tarihleri arasında yapılmıştır. Toplam 42 kistik fibrozisli hasta (20 erkek, 22 kız) çalışmaya alınmıştır. Demografik, klinik, laboratuvar ve radyolojik bulgular, ilaç kullanımı, genetik analizler dosya kayıtlarından elde edilmiştir. Serum fT4, fT3 ve TSH düzeyleri kemilüminesans immunoassay yöntemiyle DxI800 autoanalyzer (Beckman Coulter Inc, CA, USA) kullanılarak ölçülmüştür.Bulgular: Çalışma populasyonunda tanı anındaki ortalama yaş 2.9±4.4 (yıl)’di. TSH, fT4 ve fT3 değerleri ölçülen 42 hastanın 8 tanesi (%19) anormal TSH ve Ft4 düzeyine (2 aşikar hipotroidi, 6 subklinik hipotoridi) sahipti. Tiroid disfonksiyonu olan hastaların 5 tanesi (%62.5) tiroid hormon replasman tedavisi almaktaydı.Sonuç: Çalışmamızda ilk defa Türkiye’de kistik fibrozisli hastalar tiroid disfonksiyonu açısından değerlendirilmiştir. Çalışma populasyonumuzda tiroid disfonksiyonu olan 8 (%19) hasta saptadık ve bunların 5 tanesi (% 62.5) L-tiroksin tedavisi almaktaydı. Kistik fibrozisli hastalarda hipotiroidi ile ilişkili problemleri önlemek amacıyla düzenli tiroid fonksiyon testleri değerlendirmesinin bu hastalarda gerekli olduğu kanaatindeyiz., Objective: Cystic fibrosis (CF) is a life-limiting, multisystemic, autosomal recessive genetic disorder that is characterized by digestive and respiratory dysfunction contributing to growth deficit, chronic respiratory infections, progressive lung tissue damage, and premature death. CF patients have several important endocrine abnormalities including exocrine pancreatic insufficiency, poor linear growth, bone diseases, hypogonadism and thyroid dysfunction. In the present study, we aimed to investigate the prevalence of thyroid dysfunction in children with CF and evaluate the general characteristics of these patients in Turkey.Material and Methods: The study was conducted between January 2015 and June 2015. A total of 42 patients (20 male, 22 female) with CF were included in the study. Demographic information; clinical, laboratory and radiological findings; medication use, and genetic analyses were assessed from the medical records. The serum fT4, fT3 and TSH levels were measured by chemiluminescence immunoassay using a DxI800 autoanalyzer (Beckman Coulter Inc., CA, USA). Results: The mean age at the time of diagnosis of CF was 35.5±53.2 months in the study population. Eight of the 42 (19%) patients whose TSH, fT4 and fT3 levels were measured had abnormal TSH and fT4 levels (two overt hypothyroidism and six subclinical hypothyroidism). Five (62.5%) of the subjects with thyroid dysfunction were receiving thyroid hormone replacement therapy. Conclusion: Our study presents the first evaluation of the patients with CF for thyroid dysfunction in Turkey. In our study population, we detected eight (19 %) CF patients with thyroid dysfunction and five (62.5%) of them were receiving L-thyroxine treatment. In our opinion, regular evaluation of thyroid function tests in patients with CF may be necessary to prevent problems associated with hypothyroidism

Background/aim: Galanin is a neuropeptide that is shown to be involved in the regulation of food intake and glucose homeostasis. The objective of this study was to evaluate the relation of serum galanin levels with anthropometric and metabolic parameters in obese and healthy children. Material and methods: The cross-sectional study consisted of 38 obese children (mean age: 11.9 ± 3.0 years) and 30 healthy children (mean age: 11.4 ± 2.0 years). Clinical and biochemical parameters [glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), lipids, galanin, and leptin levels] were assessed. Results: Serum galanin and leptin levels were significantly higher in obese children. In obese children, galanin levels were positively correlated with fasting glucose (r = 0.398, p = 0.013), insulin (r = 0.383, p = 0.018), HOMA-IR (r = 0.375, p = 0.020), and triglycerides (r = 0.391, p=0.015). Multivariate backward regression analysis revealed that galanin levels were significantly associated with fasting glucose, insulin, HOMA-IR, and triglyceride, which explained 42.0% of the variance (r2 = 0.483, P < 0.001). Conclusions: Serum galanin levels were significantly higher in obese children than healthy controls and positively correlated with insulin resistance and triglycerides in obese children. This study suggests that galanin is associated with glucose homeostasis and lipid metabolism in childhood obesity.

Objective: Androgen insensitivity syndrome is the most common cause of 46,XY disorders of sex development (DSD). This condition is inherited from an X-linked recessive pattern, and the most common causes are inactivating mutations in the androgen receptor (AR) gene. The current study reports a novel AR gene mutation in an adolescent patient presenting with primary amenorrhea. Methods: A 16-year-old patient was admitted to our department with complaints of primary amenorrhea and a request for genetic counseling. The patient's medical history revealed that she underwent a bilateral inguinal hernia operation when she was 4 months old. The physical examination revealed that the external genitalia structure was totally consistent with a female phenotype; and according to the Tanner stages, breast and pubic hair development were stages 5 and 1, respectively. Karyotype analysis was reported to be 46,XY. Therefore, the diagnosis of complete androgen insensitivity syndrome (CAIS) was suspected, and the AR gene was sequenced. Results: AR gene mutation analysis revealed a novel hemizygous frameshift mutation (c.1629_1630insA; p.R544KfsX8) as the cause of the phenotype in this patient. Conclusion: This case report emphasizes that: (1) 46,XY DSD should be considered in the differential diagnosis of patients with a female phenotype presenting with bilateral inguinal hernia during the early infancy period, and (2) CAIS should be considered in the differential diagnosis of patients with female phenotype and breast development presenting with primary amenorrhea. Abbreviations: AIS = androgen insensitivity syndrome AMH = anti-Mullerian hormone AR = androgen receptor 17-β HSD = 17-β-hydroxysteroid dehydrogenase CAIS = complete androgen insensitivity syndrome DSD = disorders of sex development E2 = estradiol N = normal SRD5A2 = 5-alpha-reductase type 2

Copyright © 2015 by the Endocrine Society.Context: Hypergonadotropic hypogonadism presents in females with delayed or arrested puberty, primary or secondary amenorrhea due to gonadal dysfunction, and is further characterized by elevated gonadotropins and low sex steroids. Chromosomal aberrations and various specific gene defects can lead to hypergonadotropic hypogonadism. Responsible genes include those with roles in gonadal development or maintenance, sex steroid synthesis, or end-organ resistance to gonadotropins. Identification of novel causative genes in this disorder will contribute to our understanding of the regulation of human reproductive function. Objectives: The aim of this study was to identify and report the gene responsible for autosomal-recessive hypergonadotropic hypogonadism in two unrelated families. Design and Participants: Clinical evaluation and whole-exome sequencing were performed in two pairs of sisters with nonsyndromic hypergonadotropic hypogonadism from two unrelated families. Results: Exome sequencing analysis revealed two different truncating mutations in the same gene: SOHLH1 c.705delT (p.Pro235fs∗4) and SOHLH1 c.27C>G (p.Tyr9stop). Both mutations were unique to the families and segregation was consistent with Mendelian expectations for an autosomal-recessive mode of inheritance. Conclusions: Sohlh1 was known from previous mouse studies to be a transcriptional regulator that functions in the maintenance and survival of primordial ovarian follicles, but loss-of-function mutations in human females have not been reported. Our results provide evidence that homozygous-truncating mutations in SOHLH1 cause female nonsyndromic hypergonadotropic hypogonadism.

Aim: In this study, it was aimed to evaluate the clinical, antropometric and laboratory findings of female patients diagnosed with central precocious puberty and to determine the laboratory value with the best diagnostic accuracy in the diagnosis of central precocious puberty. Material and Methods: Female patients whose breast development began before the age of 8 years were included in the study. The data of the patients were obtained by retrospectively examining file records. The chronogical age, age at the time of onset of the complaint, antropometric variables, bone age and hormonal tests were recorded. The patients whose bone age/chronological age ratio was >1 and in whom pubertal response was obtained to gonodotropin releasing hormone stimulation test were considered central precocious puberty and the patients who did not meet these criteria were considered premature thelarche. Receiver operating charecteristic curve (ROC) analysis was performed to determine the diagnostic accuracy of the laboratory variables. Results: Fifty one patients with idiopathic central precocious puberty and 36 patients with premature thelarche were included in the study. In the patients with central precocious puberty, the height standard deviation score, bone age and bone age/chronological age ratio were found to be significantly higher compared to the patients with premature thelarche. The basal luteinizing hormone, basal follicle stimulating hormone, basal luteinizing hormone/follicle stimulating hormone, peak luteinizing hormone, peak follicle stimulating hormone and peak luteinizing hormone/follicle stimulating hormone values were found to be significantly higher in the patients with central precocious puberty. When the cut-off value for the peak luteinizing hormone/follicle stimulating hormone ratio was taken as >0.24, the sensitivity was found to be 100% and specificity was found to be 84%. When the cut-off value for the basal follicle stimulating hormone was taken as >1.9 IU/L, the sensitivity was found to be 71% and specificity was found to be 68%. When the cut-off value for the basal luteinizing hormone was taken as >0.1 IU/L, the sensitivity was found to be 71% and specificity was found to be 64%. Conclusions: In female children, a peak luteinizing hormone/follicle stimulating hormone ratio of >0.24 can be used in the diagnosis of central precocious puberty. However, the findings should be assessed in association with the clinical and antropometric variables.

Rabson-Mendenhall syndrome (RMS) is an autosomal recessive disorder due to mutations in the insulin receptor gene (INSR) which is mapped to 19p13.2. RMS is characterized by acanthosis nigricans, generalized lanugo, tooth and nail dysplasia, high nasal bridge, and growth retardation. A 5-year-old female patient was referred due to acanthosis nigricans and generalized lanugo. On her physical examination, severe acanthosis nigricans of the neck, axillae, the external genitalia and antecubital regions, generalized lanugo, mildly decreased subcutaneous fat, dysmorphic facial features, and polydactyly on her left hand were noted. Insulin resistance and impaired glucose tolerance were found. Sequence analysis of the INSR in the patient revealed c. 3529+ 5G > A mutation in homozygous state. RMS should be suspected in a patient with characteristic physical features and insulin resistance.

Anaphylaxis is an acute, potentially life-threatening allergic multisystemic hypersensitivity reaction. Although the anaphylaxis incidence is not clearly known, serious reactions are seen at a rate of approximately 1-3 per 10,000. Drugs are among the most common causes of anaphylactic reactions. Triptorelin acetate treatment aims to alleviate the clinical symptoms of early pubertal development, the psychological consequences and the effects on growth. Triptorelin acetate is major long-acting gonadotropin releasing hormone (GnRH) analogue. Our case diagnosed with central precocious puberty was being followed up by the pediatric endocrinology department when anaphylaxis occurred following an injection at the 18th month of treatment. Anaphylaxis with Triptorelin acetate has been reported in only two cases in the literature. Although the risk of anaphylaxis with this drug is low, the possibility should be considered and appropriate measures taken.

Background: Similar autoimmune processes (defective T-cell function) take place during the pathogenesis of aplastic anemia (AA) and Graves’ disease (GD). Antithyroid drugs used for the management of GD may induce AA and GD may occur following treatment of severe aplastic anemia (SAA). Case presentation: Clinical and laboratory investigations were performed for an 11-year-and-2-month-old girl who was referred for bilateral exophthalmus and abnormal thyroid function tests. She had been diagnosed as having severe acquired AA at the age of 8 years and had been treated with allogenic hematopoietic stem cell transplantation from her healthy human leukocyte antigen-matched sibling donor. Clinical examination revealed a weight of 32.6 kg (−0.88 standard deviation [SD] score); height, 145.7 cm (−0.14 SD score); body mass index 15.5 kg/m2 (−1.01 SD score); heart rate, 110/min; blood pressure, 128/74 mmHg; bilateral exophthalmos and an enlarged thyroid gland. The laboratory workup showed hemoglobin of 11.1 g/dL; white blood cells, 7500/mL; platelets, 172,000/mL; free thyroxine (FT4), 4.80 ng/dL (normal, 0.5–1.51); free triiodothyronine (FT3), 17.7 pg/mL (normal, 2.5–3.9); thyrotropin (TSH), 0.015 mIU/mL (normal, 0.38–5.3); antithyroglobulin peroxidase (TPO) antibody, 61.7 IU/mL (normal, 0–9); antithyroglobulin (TG) antibody, Conclusions: The association of hyperthyroidism and AA in the pediatric age group is rare. The long-term use of antithyroid drugs and radioactive iodine should be avoided due to their hematologic toxic side effects.

Galectin-1, a recently identified peptide, is primarily released from the adipose tissue. Although galectin-1 was shown to have an anti-inflammatory effect, its specific function is not clearly understood. We aimed to evaluate the relationship of serum galectin-1 levels with clinical and laboratory parameters in childhood obesity. A total of 45 obese children (mean age: 12.1 +/- 3.1 years) and 35 normal-weight children (mean age: 11.8 +/- 2.2 years) were enrolled. Clinical [body mass index (BMI), waist circumference (WC), percentage of body fat and blood pressure] and biochemical [glucose, insulin, lipids, galectin-1, high-sensitive C-reactive protein (hsCRP) and leptin levels] parameters were assessed. Serum galectin-1, hsCRP and leptin levels were significantly higher in obese children than those in normal-weight children (12.4 vs 10.2 ng/mL, p < 0.001; 3.28 vs 0.63 mg/L, p < 0.001; 8.3 vs 1.2 ng/mL, p < 0.001, respectively). In obese children, galectin-1 levels correlated negatively with fasting glucose (r = 0.346, p = 0.020) and positively with fat mass (r = 0.326, p = 0.026) and WC standard deviation score (SDS) (r = 0.451, p = 0.002). The multivariate regression analysis demonstrated that serum galectin-1 levels were significantly associated with fasting glucose and WC SDS. This study showed that obese children had significantly higher galectin-1 levels in proportion to fat mass in obese cases than those in healthy children, which may be interpreted as a compensatory increase in an attempt to improve glucose metabolism.

Aim: The aim of this study was to determine the frequency and clinical characteristics of diabetic ketoacidosis (DKA) among children diagnosed with Type I diabetes mellitus (T1DM). Materials and Methods: This study included 282 pediatric cases diagnosed with T1DM between January 1999 and June 2014. Patients were divided into three groups according to age at onset (0.5 to 5.99 years, 6.0 to 10.99 years, and 11.0 to 18.0 years) and date of onset (January 1999-December 2003, January 2004-December 2008, and January 2009-June 2014). Date and age of diagnosis, seasons of diagnosis, gender, symptoms at admission, and laboratory findings were analyzed and compared in these groups. Results: Of all the patients diagnosed with T1DM, 122 (43.2%) presented with DKA. In terms of the severity of DKA, 45.1% were mild, 32.8% moderate, and 22.1% severe. The frequency of DKA was found to increase over the years (36.4% between January 1999-December 2003, 41.7% between January 2004-December 2008, 46.5% between January 2009-June 2014). The symptom duration was significantly lower and DKA frequency was higher in ≤5 year-old patients (p

Background The clinical, laboratory, genetic properties and final height of a large cohort of patients with nonclassical 21-hydroxylase deficiency (NC21OHD) in Turkey were analyzed. Methods This multicenter, nationwide web-based study collected data. Results The mean age was 9.79±4.35 years (229 girls, 29 boys). The most common symptoms were premature pubarche (54.6%) and hirsutism (28.6%). The peak cortisol was found below 18 μg/dL in three (15.45%) patients. A mutation was detected in the CYP21A2 gene of 182 (87.5%) patients. The most common mutation was V281L. Final height in female patients who were diagnosed and treated before attaining final height or near final height was found to be shorter than the final height in female patients who were diagnosed after attaining final height or near final height. Conclusions The final height of the patients who were treated during childhood was found to be shorter than the final height of patients during the adolescent period.

Aim To evaluate the relationship between 24-h blood pressure (BP) measurements and diastolic heart function evaluated by Doppler tissue imaging and B-type natriuretic peptide (BNP) levels in children with type 1 diabetes mellitus (DM). Patients and methods A total of 32 diabetic and 18 healthy children were enrolled. Spectral Doppler analysis and tissue Doppler measurements were performed by conventional echocardiography. The 24-h ambulatory BP and serum BNP levels were measured. Results Analysis of ambulatory blood pressure monitoring (ABPM) recordings showed that median daytime diastolic BP load were significantly higher in diabetic patients compared to controls [12.35 (4.23–27.23) vs. 2.5 (0–8.7), p = 0.007]. Patients with elevated daytime systolic and diastolic BP loads had significantly higher BNP values compared to patients with normal BP load (31.4 ± 24.36 vs. 11.84 ± 11.25 pg/mL, p = 0.03 and 23.21 ± 15.12 vs. 12.12 ± 14.65 pg/mL, p = 0.03, respectively). Isovolemic contraction time (47.43 ± 7.84 vs. 42.27 ± 7.47, p = 0.045), isovolemic relaxation time (68.84 ± 10.43 vs. 58.77 ± 10.02, p = 0.02), and myocardial performance index (0.45 ± 0.10 vs. 0.37 ± 0.09, p = 0.02) as determined by tissue Doppler echocardiography were significantly high in diabetic patients compared to that of control cases. Ratio of mitral peak early diastolic flow velocity (E) to peak early diastolic myocardial velocities by tissue Doppler echocardiography (E′) was also higher in patients with elevated daytime systolic BP load (E/E′, 6.71 ± 1.97 vs. 4.91 ± 1.02, p = 0.04). Conclusion Elevated BP loads detected by 24-h ambulatory BP measurements in children with type 1 diabetes are associated with increased BNP levels and abnormal tissue Doppler echocardiography indices, indicating early stage cardiac dysfunction.

The aim of the presented study was to evaluate the prevalence of isolated hyperthyrotropinemia (IH) in obese children and the relation between anthropometric and metabolic parameters.Hospital records of the children, who presented to the Pediatric Endocrinology outpatient clinic of our institution with obesity, and age and gender-matched healthy children, who had undergone thyroid function test for any reason were retrospectively reviewed.The prevalence of IH was significantly higher in the obese group than in the controls (9.2 and 3.8 %, respectively). Body mass index-standard deviation score (BMI-SDS), thyroid-stimulating hormone (TSH), lipid parameters were significantly different in the obese group than in the control group. A positive correlation between TSH and BMI-SDS and negative correlation between TSH and free T4 (fT4) levels were found in obese subjects. Stepwise multiple linear regression analysis confirmed that BMI-SDS, fT4 and triglyceride levels were the strongest independent variables correlated with TSH level in obese subjects (r (2) = 0.046, p = 0.001).IH prevalence is higher in obese children as compared to healthy children and the increase in TSH level correlates negatively with serum fT4 and positively with BMI-SDS and triglyceride levels in obese children.

Growth hormone (GH) deficiency is the most common pituitary hormone deficiency after traumatic brain injury. Patients with GH deficiency have a reduced sweating capacity which increases the risk of developing hyperthermia. To the best of our knowledge, central fever that developed due to GH deficiency and improved with GH treatment has not yet been reported. In this article, we present a case of dramatic improvement of central fever with recombinant human GH therapy in a patient with posttraumatic GH deficiency.

Objectives To determine the frequency of vitamin D deficiency in children with familial Mediterranean fever (FMF) and to investigate the factors associated with low vitamin D status. Design and methods Forty-four patients with FMF and 39 age- and sex-matched healthy controls were enrolled in this study. Demographic data, FMF symptoms, disease duration, time to delay for diagnosis, duration of follow-up, disease severity score, MEFV gene mutation, cumulative colchicine dose, compliance to treatment and serum C-reactive protein levels were recorded for each patient. Serum 25-hydroxyvitamin D levels were measured by an original commercial kit based on chemiluminescent microparticle immunoassay (CMIA). Results The serum 25-hydroxyvitamin D levels were significantly lower in FMF patients than the healthy controls (12.9 ± 3.6 and 16.3 ± 5.5 ng/mL, respectively, P = 0.001). Vitamin D levels were similar in patients homozygous for M694V and other genotypes (11.8 ± 3.7 and 13.2 ± 3.6 ng/mL, respectively, P = 0.21). Stepwise multiple linear regression analysis confirmed that the cumulative colchicine dose was the strongest independent variable correlating with vitamin D levels (r2 = 0.194, P = 0.001). Conclusion Our results suggest that serum 25-hydroxyvitamin D levels are decreased in children with FMF. Cumulative colchicine dose appears to negatively affect vitamin D levels. The role of colchicine on vitamin D metabolism needs to be elicited.

Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. Case Report and Results: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. Conclusion: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.

Graves rsquo; disease is an autoimmune disorder presenting with hyperthyroidism and the disease is rare in childhood Two year old female patient was admitted to our clinic for her evident orbital puffiness Physical examination revealed propitosis tachycardia and a hyperpigmented spot with a diameter of 6x4 cm on the skin of the left hemithorax Evaluation of thyroid function tests showed the following values: fT4: 4 00 ng dl N: 0 8 1 9 fT3: 7 7 pg ml N: 1 57 4 71 TSH: 0 004 uIU ml N: 0 4 5 anti thyroglobulin: lt;20 IU mL N: 0 50 anti thyroid peroxidase: 45 7 IU mL N: 0 50 To distinguish Graves rsquo; disease and Mc Cune Albright syndrome TSH receptor antibody TRAb level and bone survey X ray were evaluated The TRAb level was 57 IU L N: 0 9 and there was no finding consistent with fibrous dysplasia on bone X rays Propylthiouracil was started with the diagnosis of Graves rsquo; disease In her clinical follow up propylthiouracil was switched to methimazole because of a potential risk of hepatotoxicity TRAb titers remained high and propitosis persisted There was no evidence of ophthalmopathy on orbital magnetic resonance imaging MRI In this report we described a case with Graves rsquo; disease who presented with propitosis because the disease and its ocular manifestations occur rarer in children compared to adults Mc Cune Albright syndrome was also discussed as a differential diagnosis Turk Arch Ped 2013; 48: 332 5

Objective: Studies on the clinical course of children with hyperthyrotropinemia are scarce. We aimed to evaluate the role of presentation findings in such infants to predict eventual outcome. Methods: Files of infants diagnosed as suspicious congenital hypothyroidism (CH) in the neonatal or early infancy period in the past ten years were analyzed retrospectively, and 37 patients (M/F: 20/17) with hyperthyrotropinemia diagnosed at a median age of 3.2 months were included in the study. Criteria for inclusion were: normal free thyroxine (fT4) levels and thyrotropin (TSH) levels between 10-20 μIU/mL during the initial neonatal screening (or TSH

Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders) and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%), with 8 of them (21%) having multiple problems. Six (16%) of the survivors were obese and 8 (21%) of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21%) subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21%) patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least one adverse event occurred in most of our cases. Conflict of interest:None declared.

Genetic, hormonal, and anatomical factors are believed to be involved in the etiology of undescended testes. Due to increased risk of infertility, testicular cancer, torsion and/or accompanying inguinal hernia (>90%) as well as cosmetic concerns, all these patients require treatment. In this review paper, we aimed to evaluate the success rates of treatment modalities used in undescended testes, beginning from 1930 to the present, and to draw attention to the possible risks and benefits and also the efficacy of hormonal therapy in the management of the disorder, which is still a controversial issue. Hormonal therapy may lead to penile growth, painful erection, and behavioral changes while on treatment. In recent years, it has been reported that human chorionic gonadotropin (hCG) treatment was associated with interstitial edema due to increased vascular permeability, inflammation-like changes, and several adverse effects on germ cells by increasing pressure and apoptotic process. It has also been reported that LHRH analogues have positive effects on germ cells by increasing fertility in patients undergoing unilateral or bilateral orchiopexy. In some studies, the success rate of hCG treatment was reported to be higher following buserelin. In some other studies, hCG treatment was recommended before orchiopexy to reduce the risk for surgical ischemia. There are a limited number of randomized controlled studies, so evidence showing the efficacy of hormonal therapy is insufficient. According to the 2007 Consensus Report of Nordic countries, it is recommended that surgery is the first-line treatment modality in undescended testes and that it should be performed by pediatric surgeons and urologists at the age of 6-12 months. Conflict of interest:None declared.

Summary Steroidogenic factor-1 (SF-1), also known as nuclear receptor subfamily 5 group A member 1 (NR5A1), is a member of orphan receptor subfamily and located on chromosome 9 (9q33). In 46, XY individuals with mutation of SF-1 gene, adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus, infertility can occur from severe to mild. We report a case of a 20-day-old male who is admitted to our clinic due to ambiguous genitalia. In this report, we describe a novel heterozygous c.814A > C (p. T272P) NR5A1 mutation in a patient with 46, XY DSD without adrenal insufficiency. We describe a novel missense mutation c.814A > C (p. T272P) in NR5A1 gene which had not previously been reported. Also this report highlights that the potential diagnostic utility of next-generation sequencing is an effective strategy versus Sanger sequencing to identify genetic mosaicism in clinical practice.

WOS: 000418562600010, PubMed ID: 29278518, Genital anomalies, ranging from female genitalia to milder degrees of undervirilization, are rarely reported in Klinefelter syndrome, in which a male is classically expected to be born with male external genitalia. Though androgen insensitivity syndrome (AIS) is one of the possible pathogenic mechanisms also in Klinefelter syndrome with genital anomalies, to date the AR gene has not been analyzed in any of the published cases of Klinefelter syndrome of the milder phenotype, except for those patients presenting with a severe phenotype, such as female external genitalia. Lack of interest in considering androgen insensitivity in Klinefelter syndrome with a milder phenotype of genital anomalies may impede its identification through an accurate diagnosis. We present a 14-month-old boy with penoscrotal hypospadias, micropenis, and a ventral penile chordee abnormality who was observed to have both a 47, XXY karyotype and a known missense mutation in the AR gene that was inherited from his mother. Although it is recommended that Klinefelter syndrome be considered in the differential diagnosis of penoscrotal abnormalities, mutations in specific genes involved in androgen synthesis or responsiveness should also be investigated.

The current study aimed to investigate the relationship between serum betatrophin levels and metabolic and anthropometric parameters in obese children.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".Serum betatrophin levels of the obese subjects were significantly lower than that of non-obese subjects (p0.05). Insulin resistant subjects had significantly lower betatrophin concentrations than those of non-insulin resistant subjects (p0.05). Betatrophin levels were negatively correlated with the fasting serum insulin and, accordingly insulin resistance index.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.

Background/Aim: The exon 3-deleted/full-length (d3/fl) growth hormone (GH) receptor (GHR) polymorphism has been associated with responsiveness to GH therapy in some diagnostic groups. However, there are still controversies on this issue. To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2 years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner’s syndrome (TS) and the distribution of GHR exon 3 isoforms. Materials and Methods: 218 patients with GHD (125 males/93 females) and 43 patients with TS were included in the study. The control group included 477 healthy adults aged from 18 to 57 years (54 females/423 males). Anthropometric parameters and insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually. GHR isoforms were studied using simple multiplex PCR. Height and body mass index were expressed as standard deviation score (SDS). Results: There were no differences among TS, GHD and healthy adults regarding the distribution of GHR exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in height SDS in both diagnostic groups on GH therapy; however, there were neither differences in height SDS and Δheight velocity between fl/fl, fl/d3 and d3/d3 groups nor a correlation between the distribution of GHR exon 3 isoforms and change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the diagnostic groups. There was also no gender difference in GHR isoforms in healthy adults. Conclusion: The results suggest that responsiveness to GH therapy does not depend on the exon 3 GHR genotypes in GHD and TS patients.

Deficiency of 17 beta-hydroxysteroid dehydrogenase type3 (17 beta-HSD3) isoenzyme which catalyzes the synthesis of testosterone from Delta 4-androstenedione, is the cause of 46, XY disorders of sex development (DSD). 17 beta-HSD3 deficiency is a rare autosomal recessive disorder, which is caused by mutations in the HSD17B gene found on chromosome 9q22. Up to now, almost 33 mutations in the HSD17B3 gene have been reported. Here, we report a patient with a novel mutation in HSD17B3 gene leading to 17 beta-HSD3 deficiency. The patient was admitted because of primary amenorrhea and signs of virilization at puberty. The chromosome analysis showed a 46, XY karyotype. Hormonal evaluation revealed a high Delta 4-androstenedione level with a low serum testosterone/androstenedione (T/A) ratio. Sequence analysis of HSD17B3 gene revealed the presence of a homozygous missense mutation in exon 11 resulting in a premature stop codon (p.Y287). Gonadectomy was performed after the molecular diagnosis and estrogen replacement therapy was initiated. With this report, we emphasize that 17 beta-HSD3 deficiency should be considered in virilized female patients at puberty if the T/A ratio is less than 0.8, and the molecular analysis should be performed for the precise diagnosis and genetic counseling. (C) 2014 Elsevier B.V. All rights reserved.