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Objectives: Central diabetes insipidus (CDI) is a rare but important disease of varying etiology that poses challenges in diagnosis and follow-up. Identifying diagnostic difficulties in patients with CDI will help ensure an optimal approach to their management and follow-up. This study aimed to characterize the clinical and etiological characteristics of CDI in pediatric patients., Methods: We analyzed the admission and follow-up data of CDI patients aged 0-18 years who were followed in our center between 2010 and 2019., Results: The study included 56 patients with a mean age at diagnosis of 7.92 ± 5.11 years and symptom duration of 8.65 ± 21.3 months. The patients were grouped by etiology into those with organic causes, such as structural anomalies, tumors, and trauma (group 1, n=41) and other causes (group 2, n=15). The prevalence of idiopathic CDI was 16%. At least one pituitary hormone deficiency was detected in 60.7%, the most common being thyroid stimulating hormone deficiency. Patients in group 1 had a higher mean age at diagnosis, shorter symptom duration, and higher frequency of other pituitary hormone deficiencies compared to group 2. Additionally, germinoma was detected 1 year subsequent to normal MRI findings at diagnosis and another patient was diagnosed with Langerhans cell histiocytosis (LCH) 5 years after diagnosis. All patients responded well to replacement therapies, but two patients with germinoma died during follow-up., Conclusions: In the pediatric age group, intracranial organic pathologies are an important etiology of CDI, and despite a short symptomatic period, determining the cause may be challenging and prolonged. Patients presenting at a young age with a long history of symptoms and no other pituitary hormone deficiency are unlikely to have organic CDI. However, organic causes such as LCH should be evaluated at all ages. Patients with idiopathic disease are candidates for further etiological studies, and repeated cranial imaging is important during follow-up., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups., Methods: Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group., Results: After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05)., Conclusions: In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy, in which hyperandrogenism and hyperinsulinism have both occurred. Fetuin-A, a natural inhibitor of tyrosine kinase, leads to insulin resistance. The aim was to evaluate the relationship between fetuin-A and hyperandrogenism and hyperinsulinism and the role of fetuin-A in the pathophysiology of PCOS., Methods: Thirty-eight cases with PCOS and 40 healthy adolescents were included in the study. PCOS and controls were divided into obese/non-obese subgroups. LH, FSH, total and free testosterone (TT, FT), SHBG, androstenedione, DHEAS were measured in patients with PCOS. Fasting glucose, insulin, lipid profile, AST, ALT, HsCRP, and fetuin levels of PCOS patients and healthy controls were also measured., Results: Fetuin-A levels were higher in PCOS patients than in controls. In the obese-PCOS group, when compared to non-obese PCOS patients; the levels of SHBG and HDL were low while cholesterol, LDL, triglyceride, HOMA-IR, FT, FAI, and HSCRP levels were high, but Fetuin-A levels were similar. In the obese-PCOS group, fetuin-A levels were higher than in obese-controls. HOMA-IR and fetuin-A levels were higher in non-obese PCOS patients than in non-obese controls. In the PCOS group, fetuin-A was positively correlated with TT, FT, FAI and androstenedione and negatively correlated with SHBG. Regression analysis demonstrated that FT, SHBG, and androstenedione significantly predicted fetuin-A levels (R2=54%). In non-obese PCOS patients and controls, fetuin-A was positively correlated with insulin and HOMA-IR., Conclusions: These results suggest a relationship between androgen levels and fetuin-A in PCOS cases, independent of insulin resistance, and may shed light on further studies., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Physical activity and sports can be used to reduce stress and anxiety by increasing aerobic capacity and muscle endurance, gain positive behavioral changes and improve their self-discipline, use time well, adopt positive lifestyle such as regular eating and sleeping, which will result in an increase in school success. There are no comprehensive study that examines the academic performance of licensed student athletes and the factors influencing their success rates. The aim of this study was to evaluate the academic performance and related factors in licensed athletes., Methods: One hundred eleven licensed athletes at junior high school level were enrolled. Participants filled out questionnaires specifically designed to assess for factors affecting academic performance, where personal and familial factors as well as school performance was taken into consideration. Their academic success rates were evaluated out of mean grade points before as well as after professional sports activities. Academic fields that were graded were, namely, mathematics, life sciences, language, and grammar studies as well as social sciences. Fifty one of participants lived in Ankara (Group 1) and the other 60 lived in Kahramanmaraş (Group 2). The effects of sport and other factors that may affect school success in all groups and between the groups were evaluated before and after sports., Results: The age of the athletes were 14.1 ± 2.3 years, 49.5% were male. The grades of athletes before they started competing in professional sports were 80.4 ± 10.6 for mathematics, 80.5 ± 12.5 for sciences, 82.7 ± 9.5 for language studies, and 83.6 ± 9.3 for social sciences. Following a mean period of 4.3 ± 3.1 years of professional sports, the grades of athletes were, with the same order for respective discipline were, 81.6 ± 10.9, 82.4 ± 11.9, 84.3 ± 9.4, and 85.5 ± 8.5. Following sports activities, academic performance in life sciences, language, and grammar studies as well as social sciences showed a significant improvement where grades for mathematics did not show any significant change (p=0.054). The most important factor that improves school performance is the financial status of the family. In Group 1 demonstrated grade improvements following sports activities only in social sciences, whereas Group 2 athletes showed such an improvement for all the disciplines (p<0.05)., Conclusions: Licensed athletes' school success during the junior high school period showed a significant increase after sports in this study. The most important factors that affected the academic performance were the socioeconomic status of the family., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Hair is important for individuals due to its cosmetic functions and its anatomical and physiological features. Hair loss in children significantly affects their social and psychological well-being and may lead to significant psychological distress in those not benefiting from medical and/or traditional therapies. Accordingly, the aim of the present study was to evaluate the self-esteem in children and adolescents with alopecia areata., Methods: This comparative study included children and adolescents with the diagnosis of alopecia and age- and sex-matched healthy controls. Self-esteem was evaluated by the Rosenberg Self-Esteem Scale (RSES)., Results: The study included 64 patients with alopecia (M/F, 32/32; mean age, 12.2 ± 3.0 years) and 60 healthy controls (M/F, 30/30; mean age, 12.0 ± 3.0 years). Age (p=0.64) and sex (p=1.0) distributions were similar between the groups. Of the patients, 35 had alopecia areata, 21 had alopecia universalis, and eight had alopecia totalis. The RSES score of patients was significantly higher than that of the controls (median [interquartile range], 1 [0-2] and 1 [0-1], respectively; p=0.008). The distribution of the participants according to the level of self-esteem (low, moderate, and high) based on the RSES scores revealed that, the proportion of patients with low and moderate self-esteem were significantly higher as compared with controls (p=0.001). The diagnostic subtype and sex did not affect the distribution of self-esteem scores in both groups., Conclusions: Hair loss is a significant factor affecting self-esteem of children and adolescents. Deteriorations in self-esteem may progress to psychological comorbidities if not approached, diagnosed, and treated timely and efficiently., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background Some studies have examined the effect of gonadal suppression on insulin-like growth factor-1 (IGF-1) levels and the growth velocity (GV) with conflicting results. Methods Forty-four girls treated with gonadotropin-releasing hormone analogue (GnRHa) for central precocious puberty (CPP) were included in the study. IGF-1 levels were examined at the beginning and after 12 months of treatment. Results IGF-1 and IGF-1 standard deviation score (SDS) according to chronological age (CA-IGF-1 SDS) at diagnosis were positively correlated with chronological age (CA), anthropometric measurements, stage of puberty, bone age (BA), BA-CA, follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, uterus length, endometrium thickness and ovarian volume (OV) at diagnosis (p < 0.05). There was no significant difference in IGF-1 levels after treatment. However, there was a negative correlation between ΔIGF-1 SDS and IGF-1 level, CA-IGF-1 SDS and BA-IGF-1 SDS at diagnosis (p < 0.05). There was no correlation between GV and IGF-1, ΔIGF-1. GV was negatively correlated with basal LH level at diagnosis (p = 0.008, r = -0.397). Peak LH levels of the patients who had GV-SDS < 0 were more suppressive than those of the patients who had GV-SDS > 0 after 12 months of treatment. Conclusions It was determined that the IGF-1 level and CA-IGF-1 SDS at baseline were correlated with more advanced pubertal stage prior to treatment. Initiation of treatment with a relatively high level of IGF-1 increased the risk of a decrease in the IGF-1 level. Likewise, the initiation of treatment with a relatively high LH level may increase the risk of low GV, but low GV was not related to the IGF-1 level. Increased sex steroid suppression may increase the risk of low GV.

Background The management options for Graves' disease in children are limited and there is controversy regarding optimal treatment. Remission rate with anti-thyroid drug (ATD) treatment in children is said to be lower than in adults. Definitive treatments are effective, but they often result in permanent hypothyroidism. The objective of this study was to investigate the outcome of methimazole treatment, identify significant predictors of a remission and evaluate the adverse effects of methimazole in a pediatric population of GD patients. Methods Medical records of the patients who had been diagnosed with Graves' disease were screened retrospectively. Diagnostic criteria included elevated free thyroxine (fT4) and total triiodothyronine (T3), suppressed thyroid-stimulating hormone (TSH) and either positive thyroid-stimulating immunoglobulin (TSI) or thyroid receptor antibodies (TRABs) or clinical signs suggestive of Graves' disease, for example, exophthalmos. Remission was defined as maintenance of euthyroidism for more than 12 months after discontinuing methimazole treatment. Results Of the 48 patients, provisional remission was achieved in 21 patients. Of the 21 patients, 14 experienced a relapse (66.6%). Remission was achieved in seven (24.1%) of 29 patients who received methimazole treatment for more than 2 years. In patients who achieved long-term remission, the male sex ratio and fT4 levels at diagnosis were significantly lower than the relapsed and non-remission groups, whereas the free triiodothyronine (fT3)/fT4 ratio and duration of methimazole treatment were significantly higher than the relapse group. Conclusions Long-term methimazole treatment in pediatric Graves' disease would be appropriate. High fT4 levels at the time of diagnosis and male sex were associated with a risk of relapse.

Background Understanding the role of environmental toxicant exposure on children's development is an important area of inquiry in order to better understand contextual factors that shape development and ultimately school readiness among young children. There is evidence suggesting negative links between exposure to environmental toxicants and negative physical health outcomes (i.e. asthma, allergies) in children. However, research on children's exposure to environmental toxicants and other developmental outcomes (cognitive, socioemotional) is limited. Objectives The goal of the current review was to assess the existing literature on the links between environmental toxicants (excluding heavy metals) and children's cognitive, socioemotional, and behavioral development among young children. Methods This literature review highlights research on environmental toxicants (i.e. pesticide exposure, bisphenol A, polycyclic aromatic hydrocarbons, tobacco smoke, polychlorinated biphenyls, flame retardants, phthalates and gas pollutions) and children's development across multiple domains. Results The results highlight the potential risk of exposure to multiple environmental toxicants for young children's cognitive and socioemotional development. Discussion Discussion will focus on the role of environmental toxicants in the cognitive and socioemotional development of young children, while highlighting gaps in the existing literature.

Background Current literature suggests that diet is involved in either the development of premenstrual syndrome (PMS) or contributes to symptom severity, but to date, there are no studies evaluating eating attitudes of adolescents with PMS. The aim of this study was to evaluate dietary intake and eating attitudes in adolescents with PMS. Methods This study was conducted with 383 adolescents (214 with and 169 without PMS), aged 13-19 years. PMS was diagnosed using the premenstrual syndrome scale (PMSS). The Food Frequency Questionnaire (FFQ) and 24-h dietary recall were used to assess dietary intake. The Eating Attitudes Test-26 (EAT-26) and Three Factor Eating Questionnaire-Revised 18 (TFEQ-R18) were used to evaluate eating attitudes. Anthropometrical measurements and bone mineral content were measured. Results PMS prevalence was 55.9% according to PMSS subscales. Disordered eating attitudes determined by EAT-26 was detected in 23.8% in the PMS group and 11.8% of the control group (p<0.05). In the PMS group, total TFEQ-R18 score, emotional eating behavior and uncontrolled eating behavior scores were significantly higher (p<0.001). Whereas no significant difference in dietary intake, anthropometrical measurements or bone mineral content was observed between the two groups. Conclusions This is the first study documenting that not dietary intake but eating attitudes can be associated with PMS in adolescents. It is important to understand the relationship between disordered eating behaviors and PMS as both conditions may trigger the other.

Background The short stature homeobox-containing (SHOX) gene strongly affects height. Therefore, a better understanding of SHOX haploinsufficiency could be advantageous to early diagnosis and treatment. We investigated the rate of SHOX haploinsufficiency in patients of short stature and documented their anthropometric measurements. Methods Between 2010 and 2017, we evaluated 86 patients (70 females, 16 males; age 4.3-18 years) with clinical diagnoses of short stature and Madelung deformity (MD). Clinical abnormalities are presented for patients with MD with and without SHOX haploinsufficiency as determined by fluorescence in situ hybridisation (FISH). Results According to our inclusion criteria, 78 of 86 patients (70 females, 16 males) had short stature (height <-2.5 standard deviation [SD]) and a family history suggestive of short stature. Eight patients had short stature, a family history suggestive of short stature and MD. MD was obvious in eight children in radiographic examinations. Although five of these had no deletion of SHOX, three had deletion of this gene. The deletion detection rate was 37.5% in the individuals with short stature and MD, i.e. Leri-Weill dyschondrosteosis syndrome (LWS), whilst no deletions were detected in the individuals with only short stature. One individual responded well to growth hormone (GH) treatment for the first 2 years but then developed an intolerance with persistently elevated insulin-like growth factor-1 (IGF-1) levels. Conclusions As we likely missed cases due to our methodology, the routine analysis for SHOX screening should be firstly multiplex ligation-dependent probe amplification (MLPA). The incidence of MD may have been higher in the cohort if X-rays were performed in all individuals. GH treatment was not well tolerated in one case due to persistently elevated IGF-1 levels, and long-term evaluations of patients with SHOX deficiency are required.

Background The aim of our study was to evaluate clinical, laboratory and imaging findings and to have an idea about the clinical course of subclinical hypothyroidism in children. Methods Our study included 25 patients who were diagnosed with non-autoimmune subclinical hypothyroidism without goitre, between the ages of 3 and 18 and with body mass index (BMI) below the 85th percentile. Results The mean thyroid-stimulating hormone (TSH) level was 6.92±0.92 μIU/mL at diagnosis, 4.77±1.57 μIU/mL in the third month and 4.51±1.79 μIU/mL in the first year of follow-up. About 73.7% of subclinical hypothyroidism was recovered. There was no statistically significant difference between heart rate, diastolic blood pressure, lipid profile, fasting blood glucose (FBG), fasting insulin level, homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin, white blood cell, platelet, C-reactive protein (CRP) levels and thyroid volume at diagnosis and in the first year of follow-up. In the first year of follow-up, systolic blood pressure and high-sensitivity CRP value were significantly higher than at diagnosis. However, it was observed that these values were similar in the present group with subclinical hypothyroidism. Conclusions We concluded that there was no progression to overt hypothyroidism during 1-year follow-up and that subclinical hypothyroidism had no effect on height standard deviation score (SDS), BMI SDS, blood pressure, glucose and lipid metabolism during follow-up without treatment.

Background: We aimed to evaluate the clinical follow-up data of patients with premature thelarche and determine the rate of development of precocious and early puberty in these patients., Methods: The charts of 158 girls with premature thelarche who were followed-up in our pediatric endocrinology polyclinic were reviewed. The patients were divided into three groups according to the age at onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8 years) (n=106)., Results: At admission, the mean height standard deviation score (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients were obese and 24% of the patients were overweight. The majority of patients who were obese and overweight were in group 3. At the end of the follow-up, thelarche regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic pattern in 16.5% of the patients. Precocious or rapidly progressive puberty developed in 47 of the 158 patients (29.7%). The mean age at progression to early or rapidly progressive puberty was 98.1±17.6 months. A total of 89.3% of the patients who progressed to early or rapidly progressive puberty were in group 3., Conclusions: Precocious or rapidly progressive puberty developed in 29.7% of subjects with premature thelarche. As patients who developed rapidly progressive puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested that the increase in weight could stimulate rapidly progressive puberty in cases with premature thelarche.

Background: The aim of the study was to assess the response to growth hormone (GH) treatment in very young patients with GH deficiency (GHD) through a national, multi-center study. Possible factors affecting growth response were assessed (especially mini-puberty)., Methods: Medical reports of GHD patients in whom treatment was initiated between 0 and 3 years of age were retrospectively evaluated., Results: The cohort numbered 67. The diagnosis age was 12.4±8.6 months, peak GH stimulation test response (at diagnosis) as 1.0±1.4 ng/mL. The first and second years length gain was 15.0±4.3 and 10.4±3.4 cm. Weight gain had the largest effect on first year growth response; whereas weight gain and GH dose were both important factors affecting second year growth response. In the multiple pituitary hormone deficiency (MPHD) group (n=50), first year GH response was significantly greater than in the isolated GH deficiency (IGHD) group (n=17) (p=0.030). In addition first year growth response of infants starting GH between 0 and 12 months of age (n=24) was significantly greater than those who started treatment between 12 and 36 months of age (n=43) (p<0.001). These differences were not seen in the second year. Δ Length/height standard deviation score (SDS), Δ body weight SDS, length/height SDS, weight SDS in MPHD without hypogonadism for the first year of the GH treatment were found as significantly better than MPHD with hypogonadism., Conclusions: Early onsets of GH treatment, good weight gain in the first year of the treatment and good weight gain-GH dose in the second year of the treatment are the factors that have the greatest effect on length gain in early onset GHD. The presence of the sex steroid hormones during minipubertal period influence growth pattern positively under GH treatment (closer to the normal percentage according to age and gender).

Background: There are different opinions about the effects of growth hormone replacement therapy (GHRT) on thyroid function and volume. This study aimed to assess the effects of GHRT on thyroid volume and function in the children and adolescents with growth hormone (GH) deficiency., Methods: A total of 29 patients diagnosed with GH deficiency were enrolled in the study. The control group consisted of 29 cases matched for age, gender and pubertal period with the patients. Thyroid function tests and insulin-like growth factor levels were measured, simultaneously thyroid volumes were assessed by ultrasonography at the initiation period and at the end of GHRT., Results: Thyroid volumes of the patient group was -0.55±1.1 standard deviations (SDs) initially; whereas at the end of 1 year it was found to be -0.29±1.29 SDs and both SDs of thyroid volumes did not differ significantly. The SDs of thyroid volume of the control group was -0.85±1.03 SDs initially and -0.72±0.85 SDs at the end of 1 year; and they did not differ significantly. On the other hand, after GHRT of 1 year, thyroid stimulating hormone (TSH) and free thyroxine (T4) levels decreased., Conclusions: It was observed that SDs of thyroid gland volumes did not change in GH deficient children and adolescents after GHRT.

Background: Rhizomelic chondrodysplasia punctata (RCDP) is a rare peroxisomal disease characterised by punctate calcifications of non-ossified cartilage epiphyseal centres. The main biochemical marker of all RCDP types is a decrease in the levels of plasmalogens. Additionally, the accumulation of phytanic acid can be used as a differential marker between types of RDCP. Due to the biochemical overlap between types 1 and 5 RCDP, a genetic analysis of these genes should be performed in patients to identify the type., Case Presentation: A 2-month-19-day-old male child presented with symptoms of limited movement and discomfort with movement in the extremities. His sister, who had similar clinical findings, was diagnosed with tetralogy of Fallot and died at 6 months of age. A physical examination revealed an atypical facial appearance, bilateral cataracts, sensitivity to touch in the extremities, shortness in the proximal segments of the long bones, limited movement in both knees and elbows and axial hypotonicity. Laboratory analyses revealed normal ammonia, lactate, plasma and urine amino acids, long chain fatty acids and phytanic acid levels. Rhizomelia, significant metaphyseal expansion, irregularities in the cortex, loss of ossification, fragmented appearance and punctate calcifications in both elbows, both knees and in the femoral epiphysis were seen on the skeletal survey. A homozygote p.L70W (c.209T>G) mutation was found in the PEX7 gene., Conclusions: Plasma phytanic acid levels can be normal in a patient with type 1 RCDP that develops as a result of a PEX7 gene mutation, as in our case. A molecular genetic analysis and/or fibroblast culture must be conducted in clinically suspicious cases. While no cardiac pathology was found in our case, tetralogy of Fallot was present in his sister with similar clinical findings. The presence of different cardiological phenotypes in the sibling suggested that the genotype-phenotype correlation may not be complete in this disorder.

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.

Background: Anti-Müllerian hormone (AMH) is produced by granulosa cells surrounding follicles that have undergone recruitment from the primordial follicle pool but have not been selected for dominance (preantral and early antral follicles). In healthy girls, serum levels of AMH vary considerably between individuals. We aimed to evaluate the AMH level in girls with premature thelarche (PT) and central precocious puberty (CPP)., Methods: Girls with CPP (n=21), PT (n=24) and a control prepubertal group (n=22) were included in the study., Results: AMH levels were significantly higher in the PT group than the prepubertal control group and similar to the CPP group. AMH levels in the CPP group were similar to the prepubertal control group. AMH levels showed a significant negative correlation with luteinizing hormone (LH), free testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in the PT group. AMH levels were negatively correlated with height standard deviation score (HSDS), body mass index (BMI) SDS values and positively correlated with sex hormone binding globulin (SHBG) levels in the CPP group. These levels were positively correlated with SHBG levels in the control prepubertal group., Conclusions: Serum AMH levels in girls with PT was found to be higher than in prepubertal girls. AMH levels in the CPP group were not different compared with the PT and control groups.

The calcium sensing receptor (CASR) is expressed most abundantly in the parathyroid glands and the kidney. CASR regulates calcium homeostasis through its ability to modulate parathormone secretion and renal calcium reabsorption. Inactivating mutations in the CASR gene may result in disorders of calcium homeostasis manifesting as familial benign hypocalciuric hypercalcemia (FBHH) and neonatal severe hyperparathyroidsm (NSHPT). Two cases were referred with severe hypercalcemia in the neonatal period. Laboratory evaluation revealed severe hypercalcemia and elevated PTH. The parents also had mild hypercalcemia. The serum calcium level did not normalize with conventional hypercalcemia treatment and there was also no response to cinacalcet in case 1. Total parathyroidectomy was performed when the patient was 70 days old. Genetic analysis revealed a novel homozygous p.Arg544* mutation in the CASR gene. Case 2 underwent total parathyroidectomy and autoimplantation when she was 97 days old, but the parathyroid gland implanted into the forearm was removed 27 days later because the hypercalcemia continued. Genetic evaluation revealed a novel homozygous p.Pro682Leu mutation with normal anthropometric measurements. The neurological development is consistent with age in both cases while case 2 has mild mental retardation. No bone deformity or fracture is present in either case and normocalcemia is ensured with calcitriol in both cases.

Background: Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing., Methods: A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ-ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing., Results: We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A, one has HNF4A, one has HNF1B, two have NEUROD1, one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations., Conclusions: This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.

The aim of the present study was to analyse the effects of combined treatment with calcitriol and phosphate, to find out the incidence of the nephrocalcinosis, and to elucidate the risk factor of nephrocalcinosis in patients with hypophosphatemic rickets. We followed six patients. The median age at diagnosis was 3.25 (0.75-10.5) years. The median follow-up duration was 8.25 (3.5-12.5) years. The mean dose of calcitriol and phosphate treatments was 39.1±8 ng/kg/day, 90.5±57.1 mg/kg/day, respectively. Nephrocalcinosis was detected in three patients (50%). The mean dose of phosphate taken by the patients found to have nephrocalcinosis was detected to be high with a statistically significant difference (p=0.041). No significant relationship was found the mean dose of calcitriol. We found no relationship between the development of nephrocalcinosis and the incidence of hypercalciuria or hypercalcemia episodes. We found the increased phosphate dose administered for treatment to play a role in nephrocalcinosis development.

Aim: Androgen receptor (AR) gene mutations are the leading cause of 46,XY disorders of sex development (DSD) and are associated with varying degrees of androgen insensitivity. The aim of this study is to investigate AR gene mutations in 46,XY DSD patients with normal testosterone secretion, either normal or high testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2 gene analysis, collectively, suggestive of androgen insensitivity syndrome (AIS)., Methods: We direct sequenced all eight exons of the AR gene in 21 index patients with varying degrees of undervirilization., Results: We detected AR gene alterations in five patients. In patients with complete AIS we found p.Val30Met in exon 1 and p.Gly689* in exon 4. One patient with partial AIS had p.Gln712Glu in exon 4. In two patients with partial phenotype, we found common p.Glu213Glu (c.639G>A) SNP, and an additional p.Ile817Ile (c.2451T>C) mutation was found in one of these two patients., Discussion: Despite the fact that T/DHT ratio is frequently used in diagnosis of AIS, lack of precisely determined cutoffs compromises correct diagnosis. Hence, depending on clinical and biochemical findings solely may delay correct diagnosis. Direct sequence analysis of the AR is essential for precise diagnosis of AIS.

Introduction and Purpose: This study aims to investigate the effect of Gonadotropin-releasing hormone analogues (GnRHa) treatment on anterior pituitary hormones in female children with central precocious puberty (CPP)., Subjects and Method: There were 62 female children who had been diagnosed with CPP and received GnRHa (Leuprolide acetate, 3.75 mg intramuscular/subcutaneous/28 days) included in the study. All subjects were clinically evaluated prior to treatment and every 3 months during treatment with serum LH, FSH, ACTH, TSH, PRL as pituitary hormones, and the end hormones such as plasma E2, cortisol, fT3, fT4 levels were measured. IGF-1 and IGFBP-3 levels were measured, and SDS was evaluated according to age and gender., Results: Prolactin levels were higher during GnRHa treatment compared to pre-treatment values although the increase was statistically significant only at month 3. In addition, while 2 (3.2%) of the patients had hyperprolactinemia before treatment, 11 (17.7%) patients developed hyperprolactinemia at different time points during treatment., Conclusion: This study concluded that GnRHa treatment resulted in hyperprolactinemia and had no significant effect other pituitary hormones.

Objective: In the present study, it was aimed to investigate the concomitance of additional cardiac problems, mainly mitral valve prolapse, in adolescents and pediatric patients with Hashimoto's thyroiditis, by screening autoimmune markers., Materials and Methods: Fifty-seven euthyroid patients, who applied to the Pediatric Endocrinology clinic at our institution with marked symptoms of hypothyroidism at the time of diagnosis, and were diagnosed and treated for Hashimoto's thyroiditis, were included in the present study. All patients were evaluated by performing non-organ specific autoantibodies which could be tested at our institution, thyroid ultrasonography, two-dimensional echocardiography, and 24-h holter monitorization., Results: Of the 57 cases with Hashimoto's thyroiditis, 48 (84.2%) were female, and nine (15.8%) were male. In the echocardiographic evaluation, mitral valve problems were detected in 10 (17.5%) of all cases; mitral valve prolapse was diagnosed in eight (seven females and one male) cases, and mitral insufficiency was diagnosed in two female cases. First-degree atrioventricular block was observed in only two patients during 24-h holter monitorization. Different non-organ specific autoantibody positivity was distributed as antinuclear antibody in 15 (26.3%) cases, anticardiolipin IgG in two cases, anticardiolipin IgM in three cases, tissue transglutaminase IgA in one, glutamic acid decarboxylase in one, anti-insulin antibody in four cases, antiphospholipid IgG in one, and antiphospholipid IgM in one case., Conclusion: It should be underlined that patients with Hashimoto's thyroiditis should to be followed up closely for mitral valve prolapse and accompanying autoimmune diseases.

17α-Hydroxylase/17-20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. Genetic defects causing combined 17OHD lead to the impaired production of cortisol and sex steroids, accumulation of mineralocorticoids, and compensatory overproduction of pituitary adrenocorticotropic hormone. Consequently, individuals with this enzymatic defect present with both adrenal cortical hyperplasia and variable degrees of hypertension, hypokalemia, and sexual immaturity. The patient was aged 15 years and 3 months and she was diagnosed with 17OHD while she was being evaluated for complaints of delayed puberty. In the present case, p.Y27*(c.81C>A) mutation was revealed in the sequence analysis of the CYP17A1 gene. The same mutation was reported in a 20-year-old Turkish girl in Germany, who was investigated for delayed puberty in 2005. The previous case was reported to be normotensive and normokalemic. The presence and differences in the severity of hypertension in cases with the same mutation and total enzymatic deficiency may indicate that genes predisposed to hypertension, obesity due to genetic and environmental factors, and some other factors may play a role in the clinical presentation of hypertension.

17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is present almost exclusively in the testes, and converts androstenedione (A) to testosterone (T). 17βHSD-3 deficiency is rare. The diagnosis can be missed in early childhood as the clinical presentation may be subtle. The most frequent presentation of 17 HSD-3 deficiency is a 46,XY individual with female external genitalia, labial fusion and a blind ending vagina, with or without clitoromegaly. A low testosterone/androstenedion (T/A) ratio is suggestive of 17βHSD-3 deficiency, and such diagnosis can be confirmed with molecular genetic studies. A 12-day newborn was referred to our hospital because of palpable gonads in the labia majora. On physical examination, the baby had female external genitalia and palpable gonads in the labia majora. T/A ratio was 0.26 and the diagnosis was 17βHSD-3 deficiency, which was confirmed by the evidence of compound heterozygousity novel frameshift mutations in exon 9 and 10 of HSD17B3 gene.

Vitamin D intoxication in infancy has serious consequences attributable to acute hypercalcemia and subsequent hypercalcuria or nephrocalcinosis. Traditonal treatment methods is inadequate in some patients with severe hypercalcemia due to vitamin D intoxication. Our experience suggests that bisphosphonates may be an effective and reliable drug in the treatment of severe and persistant hypercalcemia.

Congenital hypothyroidism (CH), one of the most important preventable causes of mental retardation, is a clinical condition characterized by thyroid hormone deficiency in newborns. CH is most often caused by defects in thyroid development leading to thyroid dysgenesis. The thyroid-stimulating hormone receptor (TSHR) is the main known gene causing thyroid dysgenesis in consanguineous families with CH. In this study, we aim to determine the genetic alteration in a case with congenital hypothyroidism and heart defects coming from a consanguineous family. We utilized genetic linkage analysis and direct sequencing to achieve our aim. Our results revealed that the family showed linkage to the TSHR locus, and we detected a homozygous nonsense mutation (R609X) in the case. Apart from other cases with the same mutation, our case had accompanying cardiac malformations. Although cardiac malformations are not uncommon in sporadic congenital hypothyroidism, here, they are reported for the first time with R609X mutation in a familial case.

Background: Childhood obesity is a cardiovascular risk factor., Objective: Epicardial adipose tissue (EAT) thickness, carotid intima-media thickness (IMT) and cardiac functions of obese children and their correlations were evaluated., Subjects: Five hundred obese children and 150 age- and sex-matched healthy controls., Methods: Anthropometric, laboratory data and echocardiographic measurements of IMT, EAT and cardiac functions were determined., Results: Increased M-mode echocardiographic measurements, E/e' ratios, Tei index values and decreased E/A and e'/a' ratios (where E and A are early and late mitral/tricuspid diastolic velocities, respectively, and e' and a' are peak early diastolic and peak atrial systolic myocardial velocities, respectively), were determined in the obese group. Also, carotid artery IMT and EAT thickness were significantly higher in obese children. Carotid artery IMT, EAT thickness and left ventricular mass (LVM) were found to be strongly associated with Tei index values., Conclusion: Obesity is a major risk factor for cardiovascular diseases. In our study, we showed that obese children have early subclinical systolic and diastolic dysfunctions. Also, these cardiac impairments are correlated with the increase in IMT, EAT thickness and LVM.

Introduction: Extrathyroidal abnormality incidence and especially the incidence of congenital cardiac disease are increased with congenital hypothyroidism. In this present study, it is aimed to evaluate patients who were being followed up for congenital hypothyroidism for accompanying diseases, and to compare impacts of accompanying diseases on prognosis under the light of published articles in the literature., Material and Methods: A total of 400 cases which were diagnosed with, treated and followed up for congenital hypothyroidism in our clinic were retrospectively evaluated. Cases with complaining symptoms and without any complaints, but were diagnosed with hypothyroidism as the result of screening tests were enrolled in the study., Results: Of 400 subjects included due to congenital hypothyroidism, 186 (46.5%) were girls and 214 (53.5%) were boys. Accompanying diseases were diagnosed in 113 cases (28.2%). Accompanying diseases according to the frequency order were congenital cardiac disease (n=32, 8.0%), Down syndrome (n=25, 6.3%), inguinal hernia (n=21, 5.30%), undescended testicles (n=8, 2.0%), GH deficiency (n=4, 1.0%), and some other systemic diseases (n=23, 5.8%). In cases accompanied by congenital cardiac diseases, ventricular septal defect (n=10), atrial septal defect (n=9), pulmonary stenosis (n=7), patent ductus arteriosis (n=7), and aortic coarctation (n=3) were detected., Conclusion: In this present study, it was defined that approximately one third of patients with congenital hypothyroidism had an accompanying disease, and cardiac diseases were the most common problem. It is concluded that evaluation of congenital hypothyroidism cases for accompanying diseases, detailed cardiological examination being in the first order, is important for prognosis.

Mutations in DUOX2 have been reported to cause congenital hypothyroidism (CH), and our aim in this study was to determine the genetic basis of CH in two affected individuals coming from a consanguineous family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus using microsatellite markers and then screened for mutations in linked genes by Sanger sequencing. The family showed potential linkage to DUOX2 locus and we detected a nonsense mutation (R434X) in both cases and the mutation segregated with disease status in the family. This study highlights the importance of molecular genetic studies in the definitive diagnosis and classification of CH, and it also suggests a new clinical testing strategy using next-generation sequencing in all primary CH cases.

The most common congenital endocrine disorder is congenital hypothyroidism (CH), which can lead to mental retardation if untreated. Majority of the patients have been found to have defects in thyroid development and migration disorders (dysgenesis), and the remaining ones have thyroid hormone synthesis defects (dyshormonogenesis). One of the most common mechanisms to cause dyshormonogenesis is a defect in the thyroid peroxidase (TPO) enzyme. In familial cases, mutations in the TPO gene are fairly prevalent. To date, more than 80 mutations have been identified, which result in variably decreasing TPO bioactivities. Clinical manifestations of TPO defects are typically permanent CH and with or without goiter. In this report, we presented two children with CH who were born to consanguineous parents and were homozygous carriers of a missense (G319R) TPO mutation, the mutation segregated with the disease status in the families confirming its pathogenicity. G319R mutation seemed to be a common cause of CH in Turkish population, which could originate from a common founder ancestor. Moreover, our results also confirmed the phenotypic variability associated with different TPO mutations.

Background: Factors such as vascular/neurological mechanisms, poor glycemic control, abnormalities in vitamin D/calcium, secondary hyperparathyroidism, and hypercalciuria have been blamed for the unfavorable effects of type 1 diabetes mellitus (type 1 DM) on bone health. In this present study, we aimed to evaluate the frequency of low bone mineral density (BMD) in children with type 1 DM., Method: Among 100 type 1 DM patients, a 25-hydroxy vitamin D level of <10 ng/mL was accepted as vitamin D deficiency and the level of 10-20 ng/dL was accepted as vitamin D insufficiency. BMD was measured, and Z-scores were evaluated according to adjusted Turkish standards. Participants with a Z-score of ≤-2 were defined as having low BMD; BMD between -2 and -1 were defined as being in the low range of normality; and values ≥-1 were accepted as normal., Results: The vitamin D deficiency and insufficiency ratios were 28% and 43%, respectively. Low BMD and BMD in the low range of normality were diagnosed in 10% and 25% of patients, respectively. There was no difference in vitamin D, parathormone, and metabolic control levels between three groups: with normal BMD, low BMD, and BMD in the low range of normality. BMD Z-scores were not different between the pubertal and prepubertal groups., Conclusion: Detailed evaluation should be performed for BMD in the follow-up of DM to prevent complications by decreasing related risks.

Rett syndrome is an X-linked dominant disorder frequently caused by the mutations in the methyl-CpG-binding protein 2 gene (MECP2). Its prevalence in the population is 1/15,000-20,000. Patients with Rett syndrome present apparently normal psychomotor developments during the first 6-18 months of life. Subsequently, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. Precocious puberty is characterized by premature breast and pubic hair development, and advanced bone age development at 8 years of age. We present a case of Rett syndrome and precocious puberty in a 6-year-old girl. At the age of 6, the first signs of precocious puberty appeared (Tanner stage 3). Laboratory measurements were detected as follows: luteinizing hormone (LH), 0.2 mIU/mL; follicle-stimulating hormone (FSH), 1.1 mIU/mL; estradiol, 36 pg/mL; bone age, 9 years. The response to luteinizing hormone releasing hormone (gonadotropin-releasing hormone stimulation test) was characteristic for true precocious puberty (LH, 32 mIU/mL; FSH, 26 mIU/mL). This is the first reported case of precocious puberty related to Rett syndrome.

There are different opinions concerning changes in glucose metabolism in patients with Laron syndrome. In this paper we discuss the treatment results of our patient with Laron syndrome who developed diabetes during late adolescence. A 19-year-old boy with Laron syndrome was referred to our clinic for follow-up. He had been diagnosed with Laron syndrome (LS) at 4 years old and rIGF-1 therapy was initiated. After 4 months the treatment was discontinued. At the age of 17, rIGF-1 therapy was restarted. A height gain of 8.8 cm. was observed during the 2-year treatment period. He was admitted to our hospital at the age of 19 years following discontinuation of the therapy. At that time, his height was 142 cm, and weight for height was 136%. His blood glucose was 85 mg/dL (4.72 mmol/L), insulin was 26.39 pmol/L, and HbA1c was 5.4%. At the age of 20, when he has not been receiving IGF-1 therapy for 1 year, his weight for height was 143 cm. Laboratory evaluation revealed that fasting blood glucose was 176 mg/dL (9.77 mmol/L), fasting insulin was 29.86 pmol/L, and HbA1c was 7.5%. Primary insulin therapy was then initiated. His parents both had a diagnosis of type 2 diabetes. Insulin therapy was switched to oral antidiabetic (OAD) therapy at the end of the second year because of a normal C-peptide level of 0.8 nmol/L under insulin therapy. After 6 months of OAD, HbA1c was 5.7%. The treatment was then switched to IGF-1 therapy, but his blood glucose profile was impaired and OAD therapy was restarted. In conclusion, we observed that genetic susceptibility and abdominal obesity caused type 2 diabetes in this patient. We believe that oral antidiabetic agents and life-style changes may be the appropriate approach when diabetes is developed in LS patients.

There are few reports of an association between Turner syndrome (TS) and 21-hydroxylase deficiency. However, this association is more frequent in some populations. The aim of this study was to evaluate the incidence of 21-hydroxylase deficiency in patients with TS in our population. 21-hydroxylase deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis, Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP), dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated. Patients with increased 17OHP responses in the stimulation test also underwent 21-hydroxylase gene analysis. The mean age was 14.6 +/- 4 (2.6-22.4); 37 patients were on growth hormone (GH) treatment. Nine patients were at prepubertal stage, whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP, and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic analysis. In other cases, peak 17OHP levels were < or = 6 ng/mL. The mean peak 17OHP was 2.62 +/- 1.48 (1.19-7.5) ng/mL, the cortisol level was 37.6 +/- 8.43 (23.9-56.2) microg/dL and the DHEAS was 135.2+/- 87.3 (15-413) microg/dL. The increased mean basal and peak cortisol levels (20.5 +/- 10.2 and 37.6 +/- 8.4 microg/dL) were remarkable findings. Whereas basal cortisol was above 20 microg/dL in 38.7% of patients, exaggerated results up to 56.2 microg/dL were obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were not correlated with the presence of puberty, chromosome structure, gonadal steroid use, obesity or growth hormone use. This trial suggested that 21-hydroxylase deficiency was not common among patients with TS in our population. Adrenal function should be assessed, at least in the presence of clitoral enlargement in patients with TS, particularly if their karyotype does not contain a Y chromosome.

The most common reason for refractory hypoglycemia in newborns is congenital hyperinsulinism. We report a girl with congenital hyperinsulinism due to novel homozygous mutation (c.2041-25 G>A; aberrant splicing mutation) in the ABCC8 gene encoding SUR1 and during somatostatin analog (octreotide) discontinuation developed by nonhypoglycemic seizures. The newborn (birth weight of 3,750 g) was referred to our clinic because of hypoglycemic seizures at 4 h postnatal. On admission, blood glucose was 24 mg/dL and intravenous glucose infusion was started. The patient's insulin level was 27 mIU/mL during the hypoglycemic period. Phenobarbital (5 mg/ kg/day) was added because of short-acting generalized clonic seizures. Although the patient received high doses of diazoxide, esidrex, and octreotide approximately for 2 months, hypoglycemic episodes continued. Then the patient had near-total pancreatectomy, and pathology confirmed a diffuse form of congenital hyperinsulinism. There was homozygous mutation in the ABCC8 gene encoding SUR1, which confirmed the diagnosis of autosomal recessive congenital hyperinsulinism. During octreotide discontinuation, the patient developed non-hypoglycemic seizures, which were controlled by restarting the previous doses. In the light of in vitro and in vivo studies on antiepileptic effects of somatostatin, we believe that seizures in our case have developed secondary octreotide discontinuity.

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.

Objective: The aims of this study were to analyze the role of fine-needle aspiration biopsy (FNAB) in the management of pediatric thyroid nodules and to analyze the malignancy risk of thyroid nodules by studying the association between autoimmune thyroiditis and thyroid cancer., Methods: We conducted a retrospective study on 111 patients with thyroid nodules diagnosed in childhood or adolescence. FNAB was performed in 46 participants with thyroid nodules after ultrasonography (US). Cytology diagnoses were categorized as insufficient, benign, suspicious, and malignant. Clinical and surgical follow-up data were obtained from medical records. The clinical correlation and accuracy of FNABs were evaluated., Results: The family history was positive in four patients. Forty-six patients had positive antithyroid antibodies and an inhomogeneous hypoechogenic US pattern. One patient had previous neck irradiation history. Eighty-six patients (%77.5) were euthyroid. All patients underwent US examination. The FNAB results of the 46 patients were 29 (63%) benign cases, 7 (15%) insufficient, and 10 (22%) suspicious patients. Malignancy was not reported at all. A repetition of FNAB in two benign cases, which were diagnosed with papillary carcinoma during followup, reported these cases as suspicious. Ten patients with suspicious FNAB results underwent surgery because of increases in the size of the nodules; two patients were diagnosed with papillary carcinoma. In this study, the prevalence of malignancy was 4.5% in patients with thyroid nodules., Conclusion: In this study, the importance of FNAB in the diagnosis and follow-up of thyroid nodules in childhood has been observed, and risk factors, such as history of familial thyroid carcinoma, radiotherapy to the neck at younger ages, suspicious cytological findings, and increased nodular sizes during follow-up in cases with Hashimoto thyroiditis have been correlated with increased thyroid carcinoma malignancy risk.

Objective: The aim of this study was to perform audiological evaluation of children with type 1 diabetes mellitus (DM)., Methods: One hundred DM patients (200 ears) were included in the study. Pure-tone audiometry at frequencies of 0.25, 0.5, 1, 2, 4, and 8 kHz; immittance measures including tympanometry and acoustic reflex testing; transient evoked otoacoustic emission (TEOAE); and auditory brainstem response (ABR) testing were performed in the patients. The results were statistically compared with metabolic control of DM, positive and negative autoantibodies, duration of DM, and present concomitant Hashimoto and celiac diseases., Results: The proportion with a result of 'fail' for the TEOAE test in the DM patients was not statistically significant among all groups (p > 0.05). The autoantibodies, blood glucose level, and present concomitant Hashimoto and celiac diseases were not associated with prolonged ABR latencies. However, ABR peripheral transmission time (wave I) was significantly delayed with the increasing duration of DM (p < 0.05)., Conclusion: Pediatric patients with type 1 DM do not frequently present with cochleovestibular symptoms, but show higher audiometric thresholds and the absence of or reduction in TEOAE amplitudes. In ABR testing, the increase in the peripheral transmission time (wave I) is more suggestive of retrocochlear alterations in pediatric cases of type 1 DM compared with conventional audiometric tests (e.g., pure-tone audiometry and OAEs), which may indicate possible initial auditory neuropathy. Further longitudinal investigations on a wide range of control and pediatric subjects with DM will be necessary to confirm the present data and to detect initial auditory neuropathy.

Congenital hypothyroidism (CH) is the most commonly encountered endocrinological birth defect, with an incidence of approximately 1 in 3000-4000 live births. It could be sporadic or familial as well as goitrous or non-goitrous. Inactivating mutations of TSHR , which is one of the genes responsible for non-goitrogenic congenital hypothyroidism, are mostly inherited autosomal recessively and result in a wide clinical spectrum owing to the extent of receptor function loss. Here, we report detailed clinical features of two CH cases with TSHR mutations. The first case was diagnosed before the initiation of the national screening program and had a severe clinical phenotype associated with a homozygous inactivating TSHR mutation (P556R), whereas the second case was diagnosed after the introduction of the national screening program and showed a mild clinical presentation and carried another homozygous missense mutation (P162A) in the TSHR gene. We compared the clinical features of our cases with those of previously reported patients with TSHR mutations to enhance the genotype/phenotype correlations between these mutations and corresponding clinical phenotypes.

Conn syndrome, which is rarely encountered in children, is characterized by increased aldosterone, low renin level, and arterial hypertension. Severe complications, such as impaired vascular smooth muscle function secondary to increased aldosterone, endothelial dysfunction, deterioration of left ventricular functions, acute effects on the cardiovascular system, and proteinuria, may be observed. We present a case of primary aldosteronism in a patient who has been followed up for approximately 2 years. A 15-year-old girl complained of headache lasting for approximately 1.5 years, which was diagnosed as severe hypertension. All of her systemic examinations were normal other than the hypertension. Primary aldosteronism was diagnosed on the basis of hypokalemia and alkalosis accompanied by plasma renin activity of 3.9 ng/mL/h and an aldosterone level of 1007 pg/mL (normal: 40-480). Left adrenalectomy was performed because a 10x12x12 mm adenoma was detected on abdominal magnetic resonance imaging. Although aldosterone levels returned to normal values after the surgery, antihypertensive treatment was continued because of the persistent hypertension. As the 24-h ambulatory blood pressure values of the patient were normal at 10 months after the operation, the treatment was stopped, and she was followed up for 15 months without any treatment. Since then, she has been normotensive.

Background: Oxidative stress has a critical role in inflammatory responce against tobacco smoke (TS). Testing exhaled breath condensate (EBC) samples is one of the methods used for assessment of airway inflammation caused by TS. We aimed to investigate oxidative stress in the lungs associated with TS and to evaluate the effect of this stress with pulmonary function tests (PFTs)., Methods: We included 69 subjects as three groups into the study (Group I; 26 smokers, Group II; 21 passive smokers, Group III; 22 non-smokers without TS exposure). Levels of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), nitrite/nitrate [index of nitric oxide (NO) production], vitamin C, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were measured in EBC samples collected using a condenser and PFTs were performed., Results: The levels of MDA, 8-OHdG, SOD and GSH-Px were higher in smokers. NO levels gradually increased from Group I to Group III. MDA levels were lower in Group III than Group II. The levels of vitamin C were similar in all groups. We determined negative correlation between 8-OHdG levels and forced expiratory volume in one second (FEV₁), and maximum mean expiratory flow (MMEF), and a positive correlation between SOD levels and FEV₁., Conclusions: TS exposure affected the balance between oxidative stress and antioxidant capacity of lungs. Preventing environmental TS exposure might decrease oxidative damage. Increased levels of 8-OHdG and SOD levels could be assessed as an early sign of airway damage.