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We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process.Non-obese girls who presented with the complaint of early (2-8 years) and isolated breast development were included in the study. The control group consisted of age-matched healthy prepubertal girls. Auxological measurements were performed in all subjects. Gonadotropin-releasing hormone (GnRH) stimulation test and bone age assessment were conducted in subjects with early breast development. Girls with a bone age/chronologic age ratio1.2 and a peak luteinizing hormone (LH) response to GnRH stimulation5 mIU/L were included in the PT group.The study included 22 non-obese girls with PT and 24 healthy prepubertal controls. Body mass index (BMI), BMI-standard deviation score (SDS) and height SDS were similar between the groups (p0.05). Serum leptin and nesfatin-1 levels were found significantly higher in the PT group compared to controls (p0.05). No correlation was detected between nesfatin-1 and basal LH, basal follicle stimulating hormone (FSH), stimulated peak LH, peak FSH, leptin levels and anthropometric parameters in the PT group (p0.05).Results of the present study showed that serum nesfatin-1 and leptin levels are significantly higher in girls with PT than in prepubertal controls. This finding suggests that similar to leptin, nesfatin-1 may also have a central or peripheral role in the initiation of pubertal process and may be related to PT pathogenesis.

Amac: Literaturde cocuk ve adolesan yas grubunda insulin detemirin etkinligi, gece hipoglisemi sikligindaki azalma ve kilo degisiklikleri hakkinda sinirli sayida calisma olmasi nedeniyle bu prospektif calismayi planladik. Materyal Metod: Kotu metabolik kontrollu ve/veya sabah hiperglisemileri olan 15 diyabetik hasta (10 erkek) calismaya dahil edildi. Hastalarin ortalama yasi 13.41±3.68 yil ve ortalama diyabet suresi 5.03±1.74 yildi. Hemoglobin A1c ve lipid duzeyleri, kan sekeri profilleri ve vucut kitle indeksleri baslangicta ve detemir kulanimindan 32±2.32 ay sonra degerlendirildi. Bulgular: Bazal insulin olarak insulin detemir uygulanmasindan sonra ortalama HbA1c degerleri %9.08’den %8.31’e geriledi. Total ve LDL kolesterol duzeylerinde detemir sonrasi istatiksel olarak anlamli azalma goruldu. Detemire gecildikten sonra ortalama gunluk kan sekeri profillerinde anlamli azalma saptandi. Gece hipoglisemi sikliklarinda detemire gecis sonrasi anlamli azalma saptandi. Hastalarin gunluk insulin dozlari, bolus/bazal oranlari ve BMI SDS degerlerinde anlamli bir degisiklik olmadi. Sonuc: Bu calisma, bazal - bolus rejimde gunde tek doz detemir tedavisinin NPH ile karsilastirildiginda ozellikle dislipidemi riskinin azaltilmasinda ve daha iyi metabolik kontrol saglanmasinda gece hipoglisemi riskini arttirmaksizin, etkin ve iyi tolere edilebilir oldugunu desteklemektedir.

Objective: To evaluate i) the frequency of typical hypothyroidism symptoms in children with subclinical hypothyroidism (SH), ii) to evaluate the association of SH with lipoproteins and iii) to investigate possible improving effects of L-thyroxine (LT4) treatment on these findings. Methods: Twenty-seven children with SH who had elevated thyroid-stimulating hormone (TSH: >4.94 µIU/L) but normal free T4 levels and healthy euthyroid children of similar age and sex were enrolled in the study. Anthropometric and laboratory (lipid profile and thyroid function tests) measurements were performed at diagnosis and six months after euthyroidism was achieved. All children were also subjected to a questionnaire on hypothyroid symptoms at diagnosis. The SH patients were subjected to the questionnaire also following treatment. Pre-treatment data were compared with those of controls and post-treatment measurements. Results: Anthropometric and laboratory parameters of the groups were not statistically different except for higher TSH levels in the SH group. Serum lipoprotein levels and dyslipidemia frequency were similar between the groups. Compared to the controls, hypothyroidism symptom score was significantly higher in the SH group. Six months after euthyroidism was achieved, a significant reduction in the hypothyroid symptom score was obtained in the SH group. Except for significantly higher serum TSH values, no significant differences regarding demographic characteristics, symptom scores and lipid parameters were present between patients with Hashimoto’s thyroiditis and the remaining SH patients. Conclusion: The results of this study showed that in children with SH i) the hypothyroidism symptom score was significantly higher than in euthyroid children, ii) LT4 treatment improved the hypothyroidism symptom score and iii) SH does not seem to be associated with dyslipidemia.

Subclinical hypothyroidism (SH) is defined as a serum thyroid-stimulating hormone (TSH) level above the reference range with normal serum free thyroxin (sT4) and free triiodothyronine (sT3) levels. The prevalence of SH in children and adolescents is reported between 1.7% and 9.5%. Hashimoto's thyroiditis is the most prevalent cause of SH in children. Although it has been suggested that SH is entirely an asymptomatic laboratory diagnosis, typical hypothyroid symptoms as well have been reported in some patients. Results of the adult studies on SH revealed that SH had unfavorable effects on cardiovascular system (atherosclerosis); metabolic parameters (dyslipidemia, insulin resistance, etc.); neuromuscular system; and cognitive functions in the long term. The number of studies investigating the effect of childhood SH on growth, bone maturation, lipid parameters, carbohydrate metabolism, neuromuscular system, and cognitive and cardiac function is limited. Knowledge about the natural history of SH is unclear even though there are numerous studies upon this subject. In children and adults, treatment of SH with L-T-4 is still a matter of debate, and there is no consensus on this issue yet.

The aim of the present study was to investigate the diagnostic role of serum neurokinin B level and its relationship with kisspeptin and leptin, which are known to be involved in the initiation of pubertal process. Girls who presented with breast development (1 and a peak luteinizing hormone response in gonadotropin releasing hormone stimulation test >5 mIU/L were included in the central precocious puberty group, while patients who did not meet these criteria were included in the premature thelarche group. Patients with organic pathologies were excluded. Healthy prepubertal girls with similar age were included as the control group. Leptin, kisspeptin and neurokinin B levels were measured by ELISA method. The study included 20 girls with idiopathic central precocious puberty 22 girls with premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin and neurokinin B levels were significantly higher in central precocious puberty and premature thelarche groups compared to controls, no significant difference was found between central precocious puberty and premature thelarche groups. Increased serum levels of leptin, kisspeptin and neurokinin B in patients with premature thelarche and central precocious puberty suggest that they take part during the initiation of pubertal process, however, these markers are not able to differentiate patients with central precocious puberty from premature thelarche. (C) 2015 Elsevier Inc. All rights reserved.

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

Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise molecular diagnosis is essential because it leads to optimal treatment of the patients and allows early diagnosis for their asymptomatic family members. Mutations in the glucokinase (GCK) (MODY 2) and hepatocyte nuclear factor (HNF)1A/4A (MODY 3 and MODY 1) genes are the most common causes of MODY. GCK mutations cause a mild, asymptomatic, and stable fasting hyperglycemia usually requiring no specific treatment. However, mutations in the HNF1A and HNF4A cause a progressive pancreatic beta-cell dysfunction and hyperglycemia that can result in microvascular complications. Sulfonylureas are effective in these patients by acting on adenosine triphosphate (ATP)-sensitive potassium channels, although insulin therapy may be required later in life. Mutations in the HNF1B (MODY 5) is associated with pancreatic agenesis, renal abnormalities, genital tract malformations, and liver dysfunction. Compared to MODY 1, 2, 3, and 5, the remaining subtypes of MODY have a much lower prevalence. In this review, we summarize the main clinical and laboratory characteristics of the common and rarer causes of MODY.

Neonatal diabetes mellitus is a rare clinical condition, which develops most commonly secondary to mutations in KCNJ11 and ABCC8 genes encoding ATP-sensitive K+ channels. Patients are typically diagnosed with hyperglycemia-related symptoms in the first 6 months of life and rarely with ketoacidosis. In this article, we report an infant who presented with focal clonic convulsion and thereafter was diagnosed with neonatal diabetes mellitus and thrombi in cerebral venous sinus. In this patient, after a molecular analysis of the ABCC8 gene revealed a novel heterozygous missense mutation (p.D424V), a successful transition from insulin to sulfonylurea treatment was made.

© 2015 by De Gruyter.During the first weeks of life, salt-wasting crisis, hyperkalemia, acidosis, hypoglycemia, and shock are the main findings of congenital adrenal hyperplasia (CAH). Pseudohypoaldosteronism type 1 (PHA1) is a rare disease of mineralocorticoid resistance, which is characterized with high aldosterone levels, hyponatremia and hyperkalemia without clinical findings of glucocorticoid deficiency. Patients with PHA1 are often initially diagnosed with CAH; however, it is unusual that a CAH patient is misdiagnosed as PHA1. In this report, we describe two cases with severe salt-losing crisis, hyperkalemia, and mild acidosis, which were initially diagnosed with PHA1, due to the high aldosterone levels along with normal adrenocorticotropic hormone and cortisol levels. However, subsequent investigation and genetic analysis led to the diagnosis of CAH with a homozygous I2 splice mutation in both alleles of the CYP21 gene. With this report, we emphasize that high blood levels of adrenal steroid precursors may cross-react with aldosterone and lead to confusing laboratory results that prevent making the accurate differential diagnosis between CAH and PHA1.

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.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.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.

We describe a boy, 10 years and 5 months old, who developed acute adrenal gland insufficiency which was confirmed by hormonal investigation. Abdominal magnetic resonance imaging showed unilateral enlargement of the right adrenal gland, whereas the other gland seemed normal - no cause was apparent. Three months later the patient presented with thrombosis in the right femoral vein and in the veins of the right leg. Autoantibodies against cardiolipin were strongly positive, while antinuclear antibodies and antibodies against double-stranded deoxyribonucleic acid were absent. There was no evidence of antiphospholipid syndrome associated with drugs, connective tissue disorders, or malignancies, strongly suggesting the diagnosis of primary antiphospholipid syndrome. The development of adrenal insufficiency has been reported in primary antiphospholipid syndrome due to adrenal hemorrhage following vascular occlusion of adrenal vessels or secondary to anticoagulant therapy. It was interesting to note that in our patient adrenal gland insufficiency preceded other clinical evidence of the syndrome by 3 months. The primary antiphospholipid syndrome should be considered a possible cause of Addison's disease when the etiology is not obvious. Copyright (C) 2002 S. Karger AG, Basel.

We investigated the relation of serum leptin, soluble leptin receptor (sLR) and free leptin index (FLI) with metabolic and anthropometric parameters in obese and healthy children. Height, weight, waist circumference (WC), fasting serum glucose, insulin, lipid profile, leptin and sLR levels of 35 obese children and 36 healthy children were measured and FLI was calculated as the ratio of leptin to sLR. In obese children, serum leptin and FLI were found significantly higher, while sLR level was significantly lower than the healthy children. Comparison of obese children regarding the insulin resistance showed significantly higher serum leptin and FLI in the insulin resistant group; however sLR level was not different between the insulin resistant and non-resistant obese children. In obese children, sLR was not correlated with any of the metabolic parameters except total cholesterol, while FLI was significantly and positively correlated with BMI, WC, TC, fasting insulin, and HOMA-IR. However, regression analysis confirmed that the HOMAIR was the only independent variable significantly correlated with FLI in obese children. Findings of this study suggest that in obese children and adolescents (i) serum leptin and FLI were found significantly higher, while sLR level was significantly lower than the healthy children, (ii) increased FLI might be a compensatory mechanism for increasing leptin effect in peripheral tissue, (iii) FLI is a more accurate marker to evaluate leptin resistance than leptin or sLR alone, and (iv) increased FLI may contribute toward the development of hyperinsulinemia and insulin resistance. (C) 2014 Elsevier Inc. All rights reserved.

BACKGROUND Nesfatin-1, a recently discovered anorexigenic peptide, is expressed in several tissues, including pancreatic islet cells and central nervous system. However, its pathophysiological role in the development of obesity and insulin resistance remains unknown. AIM To investigate the possible involvement of nesfatin-1 in the pathogenesis of childhood obesity, we examined the relationship between fasting and postprandial nesfatin-1 concentrations and metabolic/antropometric parameters in obese children. MATERIAL AND METHODS The study included obese children with a body mass index >95th percentile. Fasting serum glucose, insulin, lipid profile, fasting and postprandial (120th min) nesfatin-1 levels were measured to evaluate the metabolic parameters. Different cutoff values for prepubertal and pubertal stages were used to determine the status of insulin resistance (HOMA-IR) (prepubertal >2.5, pubertal >4). The percentage of body fat was measured using bioelectric impedance analysis. RESULTS Seventy-one obese children were included in this study. There was no statistically significant difference between fasting and postprandial nesfatin-1 levels in obese subjects (0.70 ± 0.15 and 0.69 ± 0.14 ng/mL, p>0.05, respectively). Insulin resistance was observed in 58% (41/71) of the cases. There was no significant difference in either fasting or postprandial serum nesfatin-1 levels between the insulin-resistant and non-resistant groups (p>0.05). There was no correlation between fasting and postprandial serum nesfatin-1 levels and anthropometric and metabolic parameters in insulin-resistant and non-resistant groups. CONCLUSIONS In this study, there was no significant increase in the postprandial level of nesfatin-1. This observation suggested that oral glucose load in obese children may not be sufficient for nesfatin-1 response and that nesfatin-1 may not have an effect as a short-term regulator of food intake.

In this study, the etiological factors, diagnostic approaches, dose, and duration of treatment were compared between cases with transient and permanent congenital hypothyroidism (CH) with respect to prognosis. One hundred and twenty-two patients who received treatments with the diagnosis of CH in the last 10 years were included in the study. The records of the patients were reviewed retrospectively. Serum thyroid- stimulating hormone (TSH) levels at the time of diagnosis were found to be significantly higher, and total thyroxine (TT4) levels were found to be significantly lower in the permanent CH group in comparison to the transient CH group. A statistically significant difference was present between the groups regarding treatment doses, the time needed for TSH decrease to5 mIU/ml and the TSH and free thyroxine (FT4) levels obtained one month after discontinuation of the treatment. The association between age at the time of initiation of treatment and results of Denver Developmental Test was noted to be statistically significant. The high frequency of transient CH in our region leads to the result that some of the patients had to be unnecessarily treated with L-thyroxine for a long time.

This is the first clinical study evaluating the relation of serum omentin 1 levels with anthropometric and metabolic parameters in obese children with a particular interest to identify the possible role of omentin 1 in childhood obesity and related metabolic disturbances.The study included obese children with a body mass index (BMI)95th percentile and healthy children with a BMI85th percentile. The healthy and obese subjects had similar age and gender distribution. Glucose, insulin, lipid profile, and omentin 1 levels were measured to evaluate the metabolic parameters.49 obese children who applied to our department with complaint of weight gain and 30 healthy age and sex matched subjects were enrolled. In obese children BMI, body mass index-standard deviation score (BMI-SDS), systolic blood pressure (SBP), diastolic blood pressure (DBP), mid-arm circumference (MAC), triceps skin fold (TSF), waist circumference (WC), homeostasis model assessment-insulin resistance (HOMA-IR), serum insulin, and triglyceride levels were higher whereas omentin-1 levels were lower than control subjects (p0.05). In the obese group, omentin 1 level was negatively correlated with BMI, insulin, HOMA-IR, and WC, while no significant correlation was observed with other parameters (p0.05). Additionally, although statistically insignificant, patients with IR (n=31) had lower omentin-1 levels compared to obese children without IR (n=18).Our data indicates that serum omentin 1 levels are i) lower in obese children and ii) negatively correlated with BMI, WC, HOMA-IR and insulin levels suggesting that omentin 1 might be a biomarker for metabolic dysfunction also in childhood and adolescence. Lower omentin 1 levels tended to be associated with insulin resistance however this association failed to reach statistical significance. Further studies in larger populations are needed to better-define the relation of omentin 1 and insulin resistance in obese children.

Objective In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH). Context Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease. Design As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families. Patients One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families. Measurements Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out. Results TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N). Conclusions This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases. WellChild Wellcome Trust European Commission European Commission QEHB Foundation Trust UK Research & Innovation (UKRI) Medical Research Council UK (MRC) (G0601811) UK Research & Innovation (UKRI) Medical Research Council UK (MRC) European Commission (G0601811) National Institute for Health Research (NIHR) (NF-SI-0508-10198)

Leptin, leptin receptor, proopiomelanocortin, prohormone convertase 1, melanocortin-4 receptor, melanocortin-3 receptor, brain-derived neurothrophic factor, neurotrophic tyrosine receptor kinase type 2, and single minded 1 genes, which are the genes that have been shown to cause monogenic obesity, are related to the leptin-melanocortin system. Congenital prohormone convertase I deficiency is a very rare syndrome characterized by early-onset obesity, small intestinal dysfunction, impaired glucose homeostasis, and disrupted prohormone processing. Obesity phenotype seen in this syndrome is known to be due to reduced melanocortin signaling in the hypothalamus which arises as a result of impaired processing of proopiomelanocortin. However, prohormone convertase 1 cleaves a number of other neuropeptides involved in feeding behavior and impaired cleavage of these neuropeptides, particularly NUCB2/nesfatin, may be a contributing factor for development of obesity in these cases. Until now, in prohormone convertase 1 deficient patients, low serum nesfatin-1 levels have not been mentioned to be a possible cause of obesity, we suggest that in these patients low levels of anorexigenic peptid nesfatin-1 might be another facilitating factor for development of obesity. (C) 2013 Elsevier Ltd. All rights reserved.

Von Hippel-Lindau syndrome is an autosomal dominant disorder that includes susceptibility to hemangioblastomas of the eyes and central nervous system, renal clear cell carcinoma, multiple pancreatic cysts, serous cystadenomas and pancreatic neuroendocrine tumors, pheochromocytoma, endolymphatic sac tumors, and cystadenomas of the epididymis and broad ligament. We present a 16-year-old male who had been followed for having bilateral adrenal, and in addition, extraadrenal multifocal pheochromocytoma for six years. At the age of 16, he presented with bilateral retinal hemangioblastomas, which led to the diagnosis of von Hippel-Lindau disease type 2A confirmed by genetic analysis. The patient's mother also had bilateral adrenal pheochromocytoma with no other von Hippel Lindau-associated tumor. In children, pheochromocytoma may be the only and/or initial manifestation of the disease with delayed manifestations of the syndrome in other organs. Von Hippel-Lindau disease is a complex multidisciplinary disorder that requires well-coordinated medical care. Surveillance of these patients and asymptomatic relatives may prevent morbidity and mortality and improve long- term prognosis. Molecular analysis of the von Hippel-Lindau gene is useful for early diagnosis of the disease in individuals who do not yet fulfill the clinical diagnostic criteria and is instrumental in the management and follow-up of the affected family.

3-M syndrome is an underdiagnosed autosomal recessive disorder characterized by severe pre- and postnatal growth retardation with minimal dysmorphic features and distinguishing radiological findings. We report a patient who was first admitted at 7.5 years of age. He was born to consanguineous parents with a birth weight of 2250 g. Physical examination revealed a severe short stature (height, 95 cm; SD score -5.64) and minimal dysmorphic features. Biochemistry, endocrine work-up, and karyotype were normal. Reevaluation at 16.5 years of age revealed a height of 128.5 cm (SD score -5.27), prominent forehead, anteverted nasal openings, fleshy nasal tip, full lips, malar hypoplasia, hyperlordosis, prominent heels, testicular volumes 8-10 mL, and pubic hair consistent with Tanner stage II. Growth hormone trial for a year resulted in inadequate height gain (3 cm). The diagnosis of 3-M syndrome was made upon typical findings (thin long bones with diaphyseal narrowing and tall lumbar vertebrae) in a recent skeletal survey. Genetic analysis disclosed a homozygote frame shift mutation in exon 2: c.457_458delinsT resulting in p.Gly153fs.

Pituitary adenoma is the most common cause of hyperprolactinemia, which is a rare endocrine disorder encountered in pediatric patient care. Epidemiological and clinical information about hyperprolactinemia in childhood and adolescence is limited. Clinical signs of hyperprolactinemia are very heterogeneous. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, headache, visual disturbances, delayed pubertal development and hypogonadism are often present. Owing to the ease of ordering a serum prolactin measurement, an evidence-based, cost-effective approach to the management of this endocrine disorder is required. Before a diagnosis of hyperprolactinemia is made, drug use, renal insufficiency, hypothyroidism, and parasellar tumors should be excluded. The main objectives of treatment are normalization of prolactin level, adenoma shrinkage, and recovery from clinical signs related to hyperprolactinemia. In patients with microadenoma, invasive or non-invasive macroadenoma, and even in patients with visual field defects, dopamine agonists are the first-line treatment. Surgical treatment is indicated in patients who are unresponsive or intolerant to medical treatment or who have persistent neurological signs. Radio therapy should be considered as a supportive treatment for patients in whom surgery fails or medical response is not achieved.

Vitamin D intoxication usually occurs as a result of inappropriate use of vitamin D preparations and can lead to life-threatening hypercalcemia. It is also known that there are a number of physicians who prescribe vitamin D supplements for various clinical conditions, such as poor appetite and failure to thrive. While inappropriate use of vitamin D supplements may lead to vitamin D intoxication, there are no reports of cases of vitamin D toxicity due to manufacturing errors of vitamin D preparations. Here, we present cases of hypervitaminosis D which developed following the use of a standard dose of a multivitamin preparation. All three cases presented with hypercalcemia symptoms and had characteristic laboratory findings such as hypercalcemia, hypercalciuria, low levels of parathyroid hormone. The very high serum 25(OH) vitamin D levels in these patients indicated vitamin D excess. The vitamin D level of the prescribed multivitamin preparation in the market was studied and was found to contain a very low level of vitamin D (10 IU/5 mL). Although the stated vitamin D content of the preparations ingested by these patients was not high, unproven but possible manufacturing errors were considered to be a possible cause of the hypervitaminosis D diagnosed in these three patients. Conflict of interest:None declared.

Background Nesfatin-1, a recently discovered anorexigenic neuropeptide, is expressed in several tissues including pancreatic islet cells and central nervous system. This peptide seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis. Objective We aimed to investigate the relation of serum nesfatin-1 level with metabolic and anthropometric parameters in obese children. Methods The study included obese children with a body mass index (BMI) above the 95th percentile and healthy children with a BMI below the 85th percentile. The healthy and obese subjects had similar age and gender distribution. Fasting serum glucose, insulin, lipid profile, and nesfatin-1 levels were measured to evaluate metabolic parameters. Results Obese group (n = 37) had significantly higher BMI, BMI-SDS (standard deviation score of BMI), triglyceride, insulin, and insulin resistance index by the homeostasis model assessment, systolic and diastolic blood pressure values compared with the control group (n = 31) (p

Neonatal diabetes mellitus (DM) is a rare condition that can be either transient or permanent. In this case report, we describe a novel mutation (p.L30Q) in the INS gene resulting in permanent DM in a four-month-old female who presented with polyphagia, polyuria, irritability, and hyperglycemia with glucosuria and ketonuria without acidosis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

The main factor influencing sex determination of an embryo is the sex-determining region Y (SRY), a master regulatory gene located on the Y chromosome. The presence of SRY causes the bipotential gonad to differentiate into a testis. However, some individuals carry a Y chromosome but are phenotypically female (46,XY females) or have a female karyotype but are phenotypically male (46,XX males). 46, XX male is rare (1:20 000 in newborn males), and SRY positivity is responsible for this condition in approximately 90% of these subjects. External genitalia of 46,XX SRY-positive males appear as normal male external genitalia, and such cases are diagnosed when they present with small testes and/or infertility after puberty. Herein, we report an adolescent who presented with low testicular volume and who was diagnosed as a 46,XX male. SRY positivity was demonstrated in the patient by fluorescence in situ hybridization method. Key words: Disorder of sexual development, XX male, SRY gene

Permanent neonatal diabetes mellitus is a rare condition mostly due to heterozygous mutations in the KCNJ11, ABCC8 and INS genes. Neonatal diabetes due to pancreatic agenesis is extremely rare. Mutations in PDX1, PTF1A, HNF1B, EIF2AK3, RFX6 and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia. This report describes a 40-day-old male infant diagnosed with permanent neonatal diabetes associated with atrial septal defect, pulmonary stenosis, patent ductus arteriosus and a novel de novo heterozygous missense mutation (p.N466S) in the GATA6 gene with no evidence of exocrine pancreas insufficiency. In addition to permanent neonatal diabetes, the patient had transient idiopathic neonatal cholestasis and hypoglycaemic episodes unrelated to insulin treatment, features that are rarely described in children with permanent neonatal diabetes. (C) 2013 Elsevier Masson SAS. All rights reserved.

Rickets is a group of diseases characterized by reduced mineralization of bone matrix in growing children. Although the most common cause is nutritional vitamin D deficiency, it may also appear as the result of hereditary diseases. Vitamin D-dependent rickets type I arises due to an autosomal recessive disturbance in renal 1 a-hydroxylase enzyme which converts 25(OH)D to 1,25(OH)2D. This condition is also called as pseudovitamin D deficiency. 25(OH)D level is normal but 1,25(OH) 2D level low. In this study, clinical and laboratory features of two cases aged 15 months and 2 years who were brought to Pediatric Endocrinology Clinic with different complaints and diagnosed with vitamin D-dependent rickets type I are presented and discussed.

Objective Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare disorder that mimics both common obesity and genetic obesity syndromes along with several endocrine disorders during early childhood. We aim to present the clinical features, laboratory and imaging results, and treatment outcomes of a patient with ROHHAD syndrome. Methods In this case report, we describe a 26-month-old boy who was admitted to our emergency department with dyspnea and cyanosis and was suspected to have ROHHAD syndrome due to his rapid-onset obesity and alveolar hypoventilation. Results A thoracal and abdominal magnetic resonance imaging was performed to demonstrate a possible accompanying neural crest tumor and it provided a yet asymptomatic retroperitoneal ganglioneuroblastoma. Based on these findings, the patient was diagnosed as ROHHADNET syndrome. Conclusion Because of the high prevalence of cardiorespiratory arrest and probability of accompanying tumors, early recognition of ROHHAD syndrome is important. To prevent presumptive mortality and morbidity, ROHHAD syndrome should be considered in all cases of rapid and early-onset obesity associated with hypothalamic-pituitary endocrine dysfunctions. (Endocr Pract. 2013;19:e13-e16)

Aarskog-Scott syndrome, also termed as faciogenital dysplasia, is an X-linked disorder consisting of short stature, craniofacial dysmorphism, shawl scrotum, cryptorchidism, and interdigital webbing. Cardiac and central nervous system abnormalities and behavioral disorders can also be detected. The gene responsible for the syndrome is called FGD1, located at Xp11.21. A 7-year-old boy was admitted to our hospital due to short stature. He was born to non-consanguineous parents after an uneventful term pregnancy. Orchiopexy for bilateral cryptorchidism was performed when he was 2 years old. At physical examination, his height was under 3 percentile, and he had broad nasal bridge, hypertelorism, wide philtrum, brachydactyly, and interdigital webbing. Cranial magnetic resonance imaging and echocardiography revealed normal findings. An eye examination showed amblyopia and astigmatism. The mother had short stature and interdigital webbing as well. Mutational analyses revealed a novel mutation ( c.308-2G), hemizygous in the boy and heterozygous in the mother. Aarskog syndrome ( faciogenital dysplasia) should be kept in mind in children with short stature and interdigital webbing.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.

AIMS The aims of this study were to determine neutrophil gelatinase-associated lipocalin (NGAL) levels in normoalbuminuric and normotensive adolescents with type 1 diabetes and to assess the relationship between NGAL and clinical and laboratory variables. METHODS Forty-six adolescents with type 1 diabetes [male/ female (M/F) ratio, 24/22; median age, 14.5 years; range, 12.2-16 years; diabetes duration, 4.8 years; range, 2.6-6.7 years; hemoglobin A1c (HbA1c), 7.9%; range, 7.2%-9.2%] and 21 healthy controls (M/F, 7/14; median age, 14.8 years; range, 13.6-15.5 years) were compared regarding clinical, laboratory, and ambulatory blood pressure monitoring variables. RESULTS Median blood and urine glucose, HbA1c, urine NGAL/creatinine ratio [13.2 (range, 8.3-43.1) vs. 4.8 (range, 2.9-20.2), p = 0.015], and daytime systolic and diastolic blood pressure (BP) standard deviation score and BP loads were found higher in diabetic adolescents. Urine NGAL levels were found to be correlated with albumin/creatinine ratio (r = 0.452, p = 0.002), whereas plasma NGAL levels were correlated with nighttime systolic BP load (r = 0.309, p = 0.037). Patients with high-normal albuminuria (n=6) had higher urine NGAL levels [48.7 ng/mL (range, 27.9-149.1 ng/mL) vs. 14.3 ng/mL (range, 3.5-41 ng/mL), p = 0.014] and urine NGAL/creatinine ratio [39.3 ng/mg (range, 21.1-126.3 ng/mg) vs. 11.8 ng/mg (range, 6.3-40.9 ng/mg), p = 0.03] compared with those of controls and higher urine NGAL levels compared with that of diabetic adolescents with low-normal albuminuria [n=40, 11.2 ng/mL (range, 6-23.4 ng/mL), p = 0.004]. CONCLUSIONS Normoalbuminuric and normotensive adolescents with type 1 diabetes have elevated urinary NGAL values, which might indicate kidney injury.

Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2 +/- 1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

AIM The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). METHODS Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. RESULTS The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). CONCLUSIONS Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Noonan syndrome is an autosomal dominant disorder characterized by short stature, typical craniofacial features, and congenital heart defects. The underlying genetic defects were not clear until 2001. This report is the first to describe a molecular analysis and associated clinical features of a Turkish mother and son, who were clinically diagnosed as Noonan syndrome when the boy was referred to our department due to short stature. The analysis revealed an A --G transition at position 923 in exon 8 of the PTPN11 gene, indicating an Asn308Ser substitution.

Objective: To assess the role of fine-needle aspiration biopsy (FNAB) in the management of pediatric thyroid nodules. Methods: Results of 30 FNABs performed in our clinic were retrospectively reviewed. Clinical and surgical follow-up data were obtained from the patient files, and clinical correlation and accuracy of FNAB were evaluated. Results: The results of 30 FNABs were reported as benign in 24 (80%), insufficient in 4 (13.3%) patients, malignant in 1 (3.3%), and suspicious in 1 (3.3%) patient. One patient with a FNAB result of malignancy underwent surgery and the histological diagnosis was papillary carcinoma. FNAB was repeated in two of the insufficient biopsies, and reported as benign; in one of these patients, the thyroid nodule disappeared and in one, remained stable at clinical follow-up. Four of the patients with benign FNAB results underwent surgery at clinical follow-up because of an increase in the size of the nodules and one patient was found to have papillary carcinoma. The remaining patients were clinically followed. In this study, the malignancy prevalence was 6.6% in patients with thyroid nodules. There was only one falsenegative case. Conclusion: FNAB is a reliable diagnostic tool in the management of pediatric thyroid nodules. © Journal of Clinical Research in Pediatric Endocrinology.

Objective To study the case of a 2 10/12-year-old boy who had growth failure and delayed bone maturation. Methods We reviewed the history, which revealed that he had had polyuria, polydipsia, lack of weight gain, and frequent vomiting since the age of 5 months. On physical examination, his height was 86 cm (-1.93 standard deviation [SD]), his weight was 10.5 kg (-2.67 SD), and he had motor and mental retardation. His maternal greatgrandfather also had polyuria and polydipsia (but not diabetes mellitus), suggesting X-linked nephrogenic diabetes insipidus as the underlying cause. The patient underwent a water deprivation-desmopressin test. The coding region of the AVPR2 gene was amplified by polymerase chain reaction and submitted to direct sequence analysis. Results The water deprivation test confirmed the diagnosis of diabetes insipidus, and administration of desmopressin did not diminish his water secretion. Direct sequencing of the AVPR2 gene revealed a novel deletion of adenine at position 222 (222delA) in exon 2. This mutation is predicted to lead to a frameshift beginning at amino acid 75 and a premature stop codon at position 115 (FS75 > 115X). His height and weight, as well as his motor skills, improved after initiation of therapy with hydrochlorothiazide and amiloride. Conclusion Growth delay can be associated with diabetes insipidus. The X-linked nephrogenic diabetes insipidus in this boy is caused by a novel mutation in the AVPR2 gene that is predicted to truncate the receptor protein. (Endocr Pract. 2010;16:231-236)

Aim To compare the long-term outcomes of continuous subcutaneous insulin infusion (CSII) pump therapy with the clinical and metabolic parameters recorded during multiple daily insulin (MDI) therapy. Patients and methods CSII pump was used by volunteer adolescents, who had a duration of diabetes mellitus (DM) longer than one year, regularly attended periodic examinations for the last year, measured and recorded blood glucose levels on average 3 to 4 times a day, and did not achieve the preferred metabolic control even though the use of MDI therapy. Carbohydrate counting and flexible MDI therapy was taught to these patients before CSII pump implantation. The metabolic and clinical parameters of the patients for the post-CSII pump period were compared with the data of flexible and non-flexible MDI periods. Results The mean CSII pump implantation age of the 17 adolescents enrolled in the study was 15.53 +/- 1.8 years, duration of DM 6.77 +/- 4.05 years, flexible MDI injection duration 0.70 +/- 0.20 years, and duration of CSII pump use 2.07 +/- 1.12 years. A decrease was detected in HbA(1c) levels of the patients with transition to CSII pump compared to flexible and non-flexible MDI injection periods; however, this decrease was not statistically significant (7.71%, 8.21%, and 8.71%, respectively, p = 0.105). No statistically significant difference was detected in frequency of hypoglycemia, lipid profiles, total daily insulin requirement, and BMI SDS values of the patients when data of the post-CSII pump state were compared with that of flexible and non-flexible MDI therapy groups. Conclusion In adolescents, it was found that CSII pump therapy is efficient and safe without any increased risk for weight gain and hypoglycemia compared to flexible and non-flexible MDI injection periods. The present study also demonstrated that flexible MDI injection therapy might be efficiently and safely used in patients who cannot receive CSII pump therapy due to social and/or financial factors.

Background: Juvenile breast hypertrophy is uncommon and is characterized by excessive breast enlargement in the peripubertal period. The clinical entity is thought to result from increased sensitivity of mammary tissue to normal levels of circulating hormones. Case: Here, we report a female patient, aged 12 years and 6 months, suffering from juvenile breast hypertrophy, who presented at the third month of symptoms and benefited from tamoxifen treatment. Comments: In experienced clinics, use of tamoxifen in the treatment of juvenile breast hypertrophy during the brisk growth period may become a medical alternative to reconstructive surgery. © 2010 North American Society for Pediatric and Adolescent Gynecology.

Few studies have been performed to investigate autoimmune diseases associated with organ non-specific rheumatological disorders in children, such as juvenile idiopathic arthritis (IA). The objective in this study was to determine the frequency of autoimmune diseases of the thyroid gland in children with JIA. Eighty patients with JIA and 81 healthy sex- and age-matched controls were enrolled in the study. Serum free T3, free T4, thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies, and anti-peroxidase antibodies were evaluated. The mean age was 11.5 +/- 5.5 years in the patient group and 10.5 +/- 4.9 years in the control group. Twenty-seven of the cases were classified as oligoarticular, 26 as polyarticular, 17 as enthesitis-related, 6 as systemic, and 4 as psoriatic arthritis. Autoimmune thyroid disease was found in 4 patients in the JIA group (5%). There were no significant differences between the study and control groups regarding the existence of anti-thyroid antibodies (p = 0.17). Girls were more likely to develop autoimmune thyroiditis (3 girls, 1 boy). Autoimmune thyroiditis was more frequent in patients who had a family history of thyroid disease (p = 0.02). There was no statistical correlation between rheumatoid factor (RF) and antinuclear antibody (ANA) positivity and autoimmune thyroiditis (p0.05). We conclude that there is no need for routine screening of serum thyroid function tests and thyroid antibody levels in patients with JIA in the absence of clinical symptoms.

Pubertal delay may be due to underlying chronic diseases and primary endocrine diseases. Celiac disease, one of the common malabsorption disorders of childhood, may progress silently in some cases, and the cases diagnosed late present with growth failure or disturbance of pubertal development. Currently, due to the changing face of celiac disease, patients are being diagnosed in adolescence with atypical symptoms and findings. This study describes 2 patients aged 13 and 16 years who presented with pubertal delay and who were diagnosed with celiac disease, concluding that routine screening of celiac disease in the differential diagnosis of delayed puberty should be recommended.

Untimely bilateral testicular enlargement greater than 3 ml is suggestive of precocious puberty, in which an underlying organic disease is more common in boys than in girls. We describe a 71/2 year-old boy presenting with testicular enlargement due to testicular microlithiasis. Following hormonal tests, diagnosis was based on ultrasonographic findings. Three years follow-up of the patient revealed normal pubertal progress and,,no., malignant evolution. Testicular microlithiasis.-is a rare cause. of testicular enlargement and pediatricians should take this disease into account in the differential diagnosis of suspected precocious puberty.

Aim: To establish the frequency and causes of vitamin D insufficiency in healthy female adolescents in Izmir, Turkey. Methods: 64 adolescents from a low- (Ikinci Inonu) and a high- (Ilica) socio-economic settlement were included. Parents' monthly income was classified as low, middle and high. The blood samples were drawn at the end of the summer and winter periods. Results: Vitamin D insufficiency percentages for the end-of-winter period were 59.4% in Ikinci Inonu and 15.6% in Ilica, and for the end of summer 25% and 15.6%, respectively. Calcidiol levels of cases from Ikinci Inonu were found to be lower compared with the levels of cases from Ilica (34 ± 15 vs 59 ± 24 nmol/l for end of winter, p =0.000; 51 ± 22 vs 65 ± nmol/l for end of summer, p =0.03). Calcidiol levels of cases whose parental monthly income was low and whose mothers were illiterate were significantly lower than the others (48 ± 18 vs 65 ± 29 nmol/l for end of summer, p=0.01; 33 ± 16 vs 56 ± 23 nmol/l for end of winter, p = 0.000; 45 ± 13 vs 64 ± 29 nmol/l for end of summer, p=0.007; 36 ± 17 vs 51 ± 25 1 for end of winter, p =0.02; respectively). Conclusion: Vitamin D insufficiency was frequent, especially in the end-of-winter period. Basic risk factors were low socio-economic status, illiteracy of mothers and low calcium intake.

Caudal dysgenesis syndrome is a rare cause of female pseudohermaphroditism. This syndrome consists of absent perineal and anal openings in association with ambiguous genitalia, urogenital, colonic, and lumbosacral anomalies. We report a case of caudal dysgenesis syndrome in an infant who had non-palpable testes, bifid scrotum, a phallus-like structure and urethral atresia. Radiological evaluation revealed bilateral hydronephrosis, bifid uterus, cervix and vagina. Caudal dysgenesis syndrome should be considered in any female infant presenting with bilateral streak ovaries, and Müllerian and genito-urinary anomalies.

The aim of this study is to determine the frequency of changes in biochemical markers of bone metabolism in children who are receiving valproic acid, carbamazepine, and oxcarbazepine. Thirty healthy children and 68 children with idiopathic epilepsy treated with either carbamazepine (n = 23), valproic acid (n = 31), or oxcarbazepine (n = 14) for more than 1 year were enrolled into the study. Blood samples were obtained in order to determine biochemical parameters (calcium, phosphorus, alkaline phosphates, parathormone, and 25-hydroxyvitamin D). Bone mineral density was measured with the dual-energy x-ray absorptiometry method. There were no significant differences in the serum concentrations of calcium, phosphorus, aspartate aminotransferase, alanine aminotransferase, and albumin levels between the four groups. However, serum alkaline phosphatase concentrations were higher in the patient group as compared with the control subjects. In patients receiving antiepileptic drugs, bone mineral density values were significantly lower than the healthy control group. In conclusion, long-term antiepileptic drug treatment either with valproic acid, carbamazepine, or with oxcarbazepine which has unknown effects on skeletal mineralization, induces a state of decreased bone mineral density. (c) 2006 by Elsevier Inc. All rights reserved.

The incidence studies on hypoglycemia in Type 1 Diabetes have revealed that the younger the child the more frequent and severe are the hypoglycemic episodes. The brain does not store glycogen and perform gluconeogenesis, it relies on a continuous supply of glucose from blood. There are several studies demonstrating the brain's ability to use lactate, alanine and ketone as alternative fuels yet there is no evidence showing that this mechanism works in diabetic individuals. During hypoglycemia, cerebral blood flow increases very little in children. It is unlikely that this mechanism alone explains the maintenance of glucose utilization. Up regulation of GLUT transporters may be an additional or alternative protective mechanism. Severe hypoglycemic episodes experienced particularly in early childhood can cause deterioration in neurocognitive functions. There are significant individual differences in terms of vulnerability to hypoglycemia. Adaptive responses to hypoglycemia might vary according to both the degree and frequency of prior hypoglycemia and the presence of structural brain changes induced by chronic hyperglycemia.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive renal tubular disorder characterized by renal magnesium wasting, hypercalciuria, advanced nephrocalcinosis and progressive renal failure. Mutations in the paracellin-1 (CLDN16) gene have been defined as the underlying genetic defect. The tubular disorders and progression in renal failure are usually resistant to magnesium substitution and hydrochlorothiazide therapy, but hypomagnesemia may improve with advanced renal insufficiency. We present a patient with a homozygous truncating CLDN16 gene mutation (W237X) who had early onset of renal insufficiency despite early diagnosis at 2 months. He also had additional abnormalities including horseshoe kidney, neonatal teeth, atypical face, cardiac abnormalities including coarctation of the aorta associated with atrial and ventricular septal defects, umbilical hernia and hypertrichosis. To the best of our knowledge, this is the youngest case diagnosed as familial hypomagnesemia with hypercalciuria and nephrocalcinosis and the first case having such additional congenital abnormalities independent of the disease itself.

Aim: Since there is limited number of studies in medical literature regarding the efficiency of in-sulin detemir, decrease in number of night hypoglycemia, weight changes and the improvement the lipid profile in pediatric and adolescent age group, we planned a prospective study to analyze abovementioned issues.Material and Method: 15 diabetic patients (10 male) with insufficient metabolic control and/ or morning hyperglisemia were included in to the study. The average age of the patients was 13.41±3.68 years and the average duration of diabetes was 5.03±1.74 years. Hemoglobin A1c levels, lipid levels and home glucose monitoring profiles were measured before and 32±2.32 months after substitution with insulin detemir.Results: After insulin detemir administration as basal insulin, the mean HbA1c values decreased from 9.08 % to 8.31 %. Total and LDL cholesterol values decreased significantly after detemir. The mean four point blood glucose profiles showed a significant decrease after the substitution with detemir. There was a decrease in the nocturnal hypoglycemia frequency and the rates were statis-tically significant differ before and after detemir. Daily insulin doses, bolus/basal rates and body mass index SDS of patients were not changed significantly before and after detemir.Conclusion: In pediatric diabetic patients, insulin detemir as basal insulin is safe and significantly lowers glucose levels compared with NPH insulin. This pilot study showed that the substitution of NPH with detemir provides a better glycemic control without increased hypoglisemic events.

Three clinical phenomena have been defined in the last decade in patients with diabetes mellitus as a dangerous iatrogenic sequel of hypoglycemia. These are hypoglycemia unawareness, defective glucose counterregulation and a lowered hypoglycemic threshold for hypoglycemic symptoms. Former mild hypoglycemia episodes cause a decrease and a delay in the protective hormonal counterregulatory response and warning symptoms in subsequent episodes, and in the absence of these, risk of severe hypoglycemia increases considerably. It has been demonstrated that when protection is provided against hypoglycemia with strict monitoring programs designed to avoid even mild hypoglycemia episodes, blunted autonomic symptoms and counterregulatory hormonal responses are rectified. Therefore, the best course of action in the treatment of pediatric diabetes mellitus is frequent blood sugar measurements, flexible multiple dose insulin regimens facilitating insulin dose adjustments as required, and a diet. In order to implement this, it is essential to organize an intensive training program with the patient and family, and to provide psychological support and close coordination with the diabetes treatment team. © Freund Publishing House Ltd.

BACKGROUND It has been reported that there is a relationship between circulating leptin and sex steroid hormones and leptin is able to stimulate estrogen secretion by increasing aromatase activity in adipose stromal cells and breast tissue. Leptin receptors have been also shown in mammary epithelial cells and it has been suggested that leptin is involved in the control of the proliferation of both normal and malignant breast cells. AIM To investigate circulating leptin levels in boys with pubertal gynecomastia. METHODS Twenty boys with pubertal gynecomastia who were in early puberty and had no obesity, and 20 healthy individuals matched for age, pubertal stage and body mass index (BMI) with the study group, were enrolled in the study. Body weight, height and left midarm circumference (MAC) and left arm triceps skinfold thickness (TSF) were measured and BMI was calculated. A fasting blood sample was collected and routine hormonal parameters including prolactin, beta-human chorionic gonadotropin (betaHCG), total and free testosterone, estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, androstenedione (AS) and dehydroepiandrosterone sulfate (DHEAS) levels were studied. Serum leptin levels were analyzed using radioimmunoassay. RESULTS The mean ages of the study and control group were not different (13.9 +/- 0.89 and 14.2 +/- 0.66, respectively). No significant difference was found for BMI, MAC and TSF values between the two groups. There was no significant difference for hormonal parameters including FSH, LH, total and free testosterone, estradiol, AS, DHEAS and estradiol/total testosterone ratio between boys with pubertal gynecomastia and the controls. Serum leptin levels were found significantly higher in the study group compared with the healthy controls (5.58 +/- 0.81 and 2.39 +/- 0.29 ng/ml, respectively; p