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Purpose: To assess the visual field sensitivity changes and investigate the association between visual field sensitivity and retinal nerve fiber layer thickness in patients with type 1 diabetes mellitus.Materials and methods: In this cross-sectional and observational study, 46 patients (22 males, 24 females) with type 1 diabetes mellitus and no diabetic retinopathy formed the diabetes mellitus group and 50 age-matched healthy subjects (32 males, 18 females) formed the control group. Retinal nerve fiber layer thickness, full-threshold standard automated perimetry, and short-wavelength automated perimetry were performed. Main outcomes were retinal nerve fiber layer thickness, mean deviation, pattern standard deviation, and short fluctuation.Results: Average retinal nerve fiber layer thickness was significantly thinner in the diabetes mellitus group (p < 0.001). The mean values of mean deviation and pattern standard deviation of the full-threshold standard automated perimetry did not differ between the groups (p = 0.179, p = 0.139, respectively). Mean short fluctuation was significantly greater in the diabetes mellitus group (p < 0.001). Both mean deviation and pattern standard deviation of the short-wavelength automated perimetry were significantly greater in the diabetes mellitus group (p < 0.001, p < 0.001, respectively). Pattern standard deviation of short-wavelength automated perimetry equal or higher than 1.57 dB had 91% sensitivity and 90% specificity (area under the curve = 0.969, p < 0.001) and short fluctuations of full-threshold standard automated perimetry equal or higher than 0.80 dB had 80% sensitivity and 76% specificity over detecting early retinal nerve fiber layer loss in patients with type 1 diabetes mellitus (area under the curve = 0.855, p < 0.001).Conclusion: This study showed that thinner retinal nerve fiber layer in patients with type 1 diabetes mellitus may be associated with abnormal retinal sensitivity to short-wavelength stimulations in short-wavelength automated perimetry; however, retinal sensitivity to white stimulus was similar to that in healthy subjects in full-threshold standard automated perimetry.

The aim of this study was to evaluate the rates of vitamin D deficiency in adolescent pregnants and its influence on the obstetric outcomes.

Primary ovarian insufficiency (POI) encompasses a spectrum of premature menopause, including both primary and secondary amenorrhea. For 75% to 90% of individuals with hypergonadotropic hypogonadism presenting as POI, the molecular etiology is unknown. Common etiologies include chromosomal abnormalities, environmental factors, and congenital disorders affecting ovarian development and function, as well as syndromic and nonsyndromic single gene disorders suggesting POI represents a complex trait.

The DUOX2 enzyme generates hydrogen peroxide (H2O2), a crucial electron acceptor for the thyroid peroxidase-catalyzed iodination and coupling reactions mediating thyroid hormone biosynthesis. DUOX2 mutations result in dyshormonogenetic congenital hypothyroidism (CH) that may be phenotypically heterogeneous, leading to the hypothesis that CH severity may be influenced by environmental factors (e.g., dietary iodine) and oligogenic modifiers (e.g., variants in the homologous reduced form of NAD phosphate-oxidase DUOX1). However, loss-of-function mutations in DUOX1 have not hitherto been described, and its role in thyroid biology remains undefined.

If turner syndrome (TS) patients have a Y-containing cell line, they have an increased risk for gonadal tumors. TS patients are therefore screened for Y-chromosome and Y-specific sequences, such as SRY, DYZ1, DYZ3, DYS132, ZFY, TSPY, etc. In addition, since the dysgenetic gonad may include the stroma and granulosa/sertoli cells, which produce androgens, virilization can seen in girls with Y-chromosomal material. Prophylactic gonadectomy may therefore be required for optimal management in such patients. Our aim is to discuss our observations in the follow-up of TS patients.

Context:Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHRunderlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken.Objective:Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD,and TSHR) in CH cases with GIS.Patients, Design, and Setting:We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico.Results:Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG(12), TPO(four), DUOX2(two), and TSHR(one). Ten cases harbored triallelic (digenic) mutations: TGand TPO(one); SLC26A4and TPO(three), and DUOX2and TG(six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases.Conclusions:The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHRor known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TGor TPOmutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (∼41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated.

Purpose To compare the anterior segment parameters of patients with juvenile diabetes mellitus (DM) and healthy children by optical biometry.Methods This prospective controlled clinical trial included 47 patients with juvenile type 1 DM and 50 age- and sex-matched healthy children. Central corneal thickness (CCT), aqueous depth (AD), lens thickness (LT), axial length, pupillary diameter (PD), K1 and K2 keratometry, and white to white distance (WTW) measurements were performed with optical biometry. The glycosylated hemoglobin (HbA1c) levels of the DM cases were obtained. Kolmogorov-Smirnov test, ttest, χ2test, and Pearson correlation test were used for statistical analysis.Results The mean age of the 20 boys and 27 girls with DM was 10.91 ± 3.24 years and the mean age of the 29 healthy boys and 21 girls was 11.61 ± 3.6 years (age p = 0.42; sex p = 0.09). The mean LT was thicker (p = 0.001), the mean AD was lower (p = 0.001), and the mean PD was smaller (p = 0.001) in the DM cases and all were statistically significant. There was no significant difference between the groups for AU, CCT, WTW, or K1 and K2 (p = 0.12; p = 0.83; p = 0.54; p = 0.97; p = 0.21, respectively). We also found a significant negative correlation between HbA1c levels and PD (r= −0.37 p = 0.01).Conclusions Juvenile DM may affect anterior segment parameters and cause thicker LT, smaller PD, and lower AD. These effects may change the refractive status and should be considered during the examination of these children.

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 CASRgene 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 CASRgene. 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.

Aim:The causes of gonadotropin-independent precocious puberty are diverse, and often have overlapping clinical and biochemical features. With the exception of congenital adrenal hyperplasia (CAH), disorders that cause gonadotropin-independent precocious puberty (GIPP) are uncommon. The literature is devoid of any large-scale studies on the etiologic distribution of GIPP. The aim of this study was to determine the frequency of each etiology in a cohort of patients with GIPP (excluding those with CAH), and to evaluate the clinical and laboratory features of these patients.Materials and Methods:This multicenter, nationwide web-based study collected data on patients who presented with non-CAH GIPP in Turkey.Results:Data were collected for 129 patients (102 girls and 27 boys) from 29 centers. Based on the data collected, the estimated prevalence of non-CAH GIPP in the studied population was 14 in 1 000 000 children. Functional ovarian cyst was the most common etiology, accounting for 37% of all cases, followed by McCune-Albright syndrome (MAS) (26%). Among the patients with MAS, 11.7% had fibrous dysplasia, 32.3% had café-au-lait spots, and 52.9% had both. Human chorionic gonadotrophin-secreting tumors included choriocarcinoma of the liver, hepatoblastoma, and germ cell tumors of the sellar-suprasellar region and mediastinum. Patients with adrenocortical tumors presented at an earlier age than those with other etiologies. Ovarian tumors included mature cystic teratoma, dysgerminoma, juvenile granulosa tumor, and steroid cell tumor. Despite overlapping features, it was possible to identify some unique clinical and laboratory features associated with each etiology.Conclusion:This largest cohort of patients with non-CAH GIPP to date yielded an estimation of the frequency of non-CAH GIPP in the general pediatric population and showed that girls were affected at a rate 4-fold greater than that of boys owing to functional ovarian cysts and MAS, which were the two most common etiologies. The data collected also provided some unique characteristics associated with each etiology.

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 MODYgenes in Turkish children by using targeted next generation sequencing.

Context:Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management.Objective:The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology.Design:A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded.Setting:The study was conducted in 19 tertiary pediatric endocrinology clinics.Patients:Ninety-five children (48 females, aged 0–18 y, eight familial) with PAI of unknown etiology participated in the study.Results:A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R(n = 25), NR0B1(n = 12), STAR(n = 11), CYP11A1(n = 9), MRAP(n = 9), NNT(n = 7), ABCD1(n = 2), NR5A1(n = 1), and AAAS(n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds+1delG in MRAP. Several important clinical and molecular insights emerged.Conclusion:This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future.

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 ARgene mutations in 46,XY DSD patients with normal testosterone secretion, either normal or high testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2gene analysis, collectively, suggestive of androgen insensitivity syndrome (AIS).

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.

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).

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.

To investigate the specific mutations in PROP1, POU1F1, LHX3,and HESX1genes in patients with combined pituitary hormone deficiency (CPHD) in Turkey. Seventy-six patients with CPHD were included in this study. Based on clinical, hormonal, and neuro-radiological data, relevant transcription factor genes were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Total frequency of mutations was 30.9 % in patients with CPHD. Frequency was significantly higher in familial patients (p= 0.001). Three different types of mutations in PROP1gene (complete gene deletion, c.301-302delAG, a novel mutation; IVS1+2T>G) were found in 12 unrelated patients (21.8 %). Mutations in PROP1gene were markedly higher in familial than in sporadic cases (58.8 vs. 5.3 %, p< 0.001). Homozygous complete gene deletion was the most common mutation in PROP1gene (8/12) and was identified in six familial patients. Four different homozygous mutations [p.Q4X, novel mutations; exons 1–2 deletion, p.V153F, p.I244S] were detected in POU1F1gene. Central precocious puberty was firstly observed in a sporadic-male patient with homozygous POU1F1(p.I244S) mutation. A homozygous mutation in HESX1gene (p.R160H) was detected in one patient. This study is the first to investigate specific mutations in CPHD patients in Turkey. Complete deletion in PROP1gene was the most common mutation encountered in patients with CPHD. We believe that the results of this study will contribute to the establishment of genetic screening strategies in Turkey, as well as to the studies on phenotype–genotype correlations and early diagnosis of CPHD patients.

Purpose To evaluate the optic disc topography parameters of children with congenital isolated growth hormone deficiency (GHD) using the Heidelberg retina tomograph (HRT) in a controlled study.Methods This prospective study included 32 eyes of 32 patients with congenital isolated GHD and 36 eyes of 36 healthy subjects. The topographic optic disc parameters (mean cup volume, rim volume, cup area, disc area, rim area, mean cup-to-disc ratio and cup depth, retinal nerve fiber layer thickness [RNFL]) were imaged in all subjects with HRT-III (software 3.01 a-M). Pearson correlation analysis was used to investigate the correlation between right and left eyes regarding the optic disc parameters. Differences between the 2 groups were evaluated by independent t test, Mann-Whitney U test, and chi-square test.Results The mean RNFL thickness in children with congenital isolated GHD was found to be statistically significantly thinner than in healthy subjects (p<0.05). However, no statistically significant differences were found between the mean cup volume, rim volume, cup area, disc area, rim area, mean cup-to-disc ratio and cup depth, and mean sectorial RNFL thickness (p>0.05).Conclusions The results suggest that congenital GHD may lead to thinner RNFL thickness when compared with healthy subjects. This indicates that GH has an important role in the development of the neural retina.

AbstractCongenital 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 TSHRlocus, 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.

AbstractObjective:To evaluate heart rate variability by Holter monitoring in type 1 diabetic children compared with a healthy control group and determine the factors modifying heart rate variability. Methods:This was designed as a prospective study comparing 28 patients, diagnosed with type 1 diabetes and under follow-up, with 27 healthy control group subjects. Results:The patients were aged 9.9 ± 4.2 years in the diabetic group, including 13 (46.5%) girls and 15 (53.5%) boys. The healthy control group comprised 20 (74%) girls and seven boys (26%) with an average age of 8.6 ± 3.7 years. The search for factors modifying heart rate variability yielded the following correlations: for the time-dependent variables, negative between age and both average and maximal heart rate (r = −0.263 and −0.460, respectively), negative between haemoglobin A1c and percentage of differences between adjacent RR intervals >50 ms, positive between diabetes duration and square root of the mean of the sum of squares of differences between adjacent NN intervals. The average heart rate and percentage of differences between adjacent RR intervals >50 ms was significantly higher in the girls than the boys in all groups. With regard to the frequency-dependent factors affecting heart rate variability, correlations were found between haemoglobin A1c level and both total power and very low frequency (r = −0.751 and −0.644) and between very low frequency and diabetes duration. Conclusion:A reduction in heart rate variability parameters was observed in type 1 diabetes mellitus patients who had a long disease duration or were poorly controlled, as compared with healthy controls.

Purpose To evaluate central corneal thickness (CCT) values in patients with Turner syndrome (TS) and compare these values with healthy subjects.Methods A total of 31 subjects with TS and 67 age- and sex-matched healthy subjects made up the study and control group, respectively. The CCT values were measured by an ultrasound pachymeter in this cross-sectional prospective study. The ocular findings were recorded. We also evaluated to effect of karyotype analysis, recombinant growth hormone therapy (GHT), and mean duration of treatment on the CCT parameter in patients with TS.Results The mean CCT values were 582.0 ± 40.8 μm (490-648) in the TS and 549.1 ± 34.6 μm (494-601) in the healthy group. The mean intraocular pressure (IOP) by Goldmann applanation tonometry was 16.3 ± 3.1 mm Hg (9-22) in the TS and 15.2 ± 2.5 mm Hg (10-21) in the healthy group. The mean CCT value was significantly higher in the TS group (p<0.05) but there was no statistically significant difference between the 2 groups for IOP (p>0.05). There was also no significant difference for CCT regarding the karyotype, GHT use, and mean duration of treatment in patients with TS (p>0.05).Conclusions Central corneal thickness values should be considered during measurement of IOP in individuals with TS as these values may be higher than in healthy subjects.

AbstractIntroduction: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.

AbstractMutations in DUOX2have 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 DUOX2locus 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.

AbstractThe 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.

AbstractBackground: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.

Obesity is a worldwide epidemic. In recent years, increasing attention has been focused on thyroid function in obesity.To establish the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents, and identify the relationship between TSH levels and other metabolic and hormonal variables before and after weight reduction.We evaluated 150 obese subjects (aged 3–17 years) for anthropometric, biochemical, metabolic and hormonal variables. Measurements were taken at baseline and, in a subgroup of children with hyperthyrotropinemia, after a 6-month intervention program based on exercise, behavior therapy, and nutrition education.At baseline, 23 participants (15.3 %) had hyperthyrotropinemia, and 21 of these patients completed the weight reduction intervention. Among these 21 patients, 14 had substantial weight loss and a significant decrease in TSH and free T3 levels.We conclude that TSH and T3 levels are significantly increased in childhood obesity; in most cases, however, these increases cannot be elucidated by thyroid autoimmunity or iodine deficiency. If thyroid disorders are excluded beforehand, an elevated TSH with normal thyroid hormone levels in obese children seems rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated TSH levels. In this context, thyroid hormone alterations in obesity suggest an adaptation process.

AbstractCongenital 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 TSHRmutations. The first case was diagnosed before the initiation of the national screening program and had a severe clinical phenotype associated with a homozygous inactivating TSHRmutation (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 TSHRgene. We compared the clinical features of our cases with those of previously reported patients with TSHRmutations to enhance the genotype/phenotype correlations between these mutations and corresponding clinical phenotypes.

AbstractObjective: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 follow-up, 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.

Abstract: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 ≤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) μg/dL and the DHEAS was 135.2±87.3 (15–413) μg/dL. The increased mean basal and peak cortisol levels (20.5±10.2 and 37.6±8.4 μg/dL) were remarkable findings. Whereas basal cortisol was above 20 μg/dL in 38.7% of patients, exaggerated results up to 56.2 μg/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.

AbstractObjective: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 tympano\xadmetry 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.

AbstractCongenital 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 multicase 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 TSHRmutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHRmutations and a PAX8mutation but no mutations in TSHBand NKX2-5. None of the biallelic TSHRmutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHRmutations and resulting clinical presentations. Here we conclude that TSHRmutations 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.

AbstractConn 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 ~2 years. A 15-year-old girl complained of headache lasting for ~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 10×12×12 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.