Hashimoto's thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents in iodine replete areas. To find out the clinical, epidemiological and laboratory characteristics of the disease in childhood, we reviewed files of 162 children and adolescents with HT followed in the Department of Pediatric Endocrinology, Hacettepe University Faculty of Medicine. Female patients constituted 86.4% (n = 140) of all patients with a female:male ratio of 6.4. Mean age at diagnosis was 11.4 +/- 2.97 years (age range 4.4-16.5 years). At the time of diagnosis 43.2% of the patients (n = 70) were euthyroid, 24.1% (n = 39) had subclinical hypothyroidism, 21% (n = 34) had overt hypothyroidism, and 8.6% (n = 14) had overt and 3.1% (n = 5) subclinical hyperthyroidism. Autoimmune thyroiditis is more frequent in females, and increases in frequency over age during childhood and adolescence. At the time of diagnosis, frequency of overt and subclinical hypothyroidism is similar to that of euthyroid goiter.

Background: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey.Design and methods: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed.Results: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3),ABCC8(n=1) and homozygousINS(n=1). In permanent neonatal diabetes (PNDM) patients, homozygousGCK(n=6),EIF2AK3(n=3),PTF1A(n=3), andINS(n=1) and heterozygousKCNJ11(n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distalPTF1Aenhancer. Both patients with aKCNJ11mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>AINSmutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births.Conclusions: Homozygous mutations inGCK,EIF2AK3and the distal enhancer region ofPTF1Awere the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.

Gonadotropin stimulation test is the gold standard to document precocious puberty. However, the test is costly, time-consuming and uncomfortable. The aim of this study was to simplify the intravenous gonadotropin-releasing hormone (GnRH) stimulation test in the diagnosis of precocious puberty and in the assessment of pubertal suppression. Data pertaining to 584 GnRH stimulation tests (314 tests for diagnosis and 270 for assessment of pubertal suppression) were analyzed. Forty-minute post-injection samples had the greatest frequency of "peaking luteinizing hormone (LH)" (p<0.001) in the diagnostic tests when the cut-off value was taken as 5 IU/L for LH, 40th minute sample was found to have 98% sensitivity and 100% specificity in the diagnosis of precocious puberty, while the sensitivity and specificity of the 20th minute sample was 100% in the assessment of pubertal suppression. LH level at the 40th minute post-injection in the diagnosis of central precocious puberty and at the 20th minute post-injection in the assessment of pubertal suppression is highly sensitive and specific. A single sample at these time points can be used in the diagnosis of early puberty and in the assessment of pubertal suppression.

Background Given the rarity of 11β-hydroxylase deficiency (11βOHD), there is a paucity of data about the differences in clinical and biochemical characteristics of classic (C-11βOHD) and nonclassic 11βOHD (NC-11βOHD). Objective To characterize a multicenter pediatric cohort with 11βOHD. Method The clinical and biochemical characteristics were retrospectively retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. Results 102 patients (C-11βOHD, n = 92; NC-11βOHD, n = 10) from 76 families (46,XX; n = 53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female adult height was 152 cm [−1.85 SD score (SDS)] and male 160.4 cm (−2.56 SDS).None of the NC-11βOHD girls had ambiguous genitalia (C-11βOHD 100%), and none of the NC-11βOHD patients were hypertensive (C-11βOHD 50%). Compared to NC-11βOHD, C-11βOHD patients were diagnosed earlier (1.33 vs 6.9 years; P < 0.0001), had higher bone age-to-chronological age (P = 0.04) and lower adult height (−2.46 vs −1.32 SDS; P = 0.05). The concentrations of 11-oxygenated androgens and 21-deoxycortisol were low in all patients. The baseline ACTH and stimulated cortisol were normal in NC-11βOHD. Baseline cortisol; cortisone; 11-deoxycortisol; 11-deoxycorticosterone and corticosterone concentrations; and 11-deoxycortisol/cortisol, 11-deoxycorticosterone/cortisol, and androstenedione/cortisol ratios were higher in C-11βOHD than NC-11βOHD patients (P < 0.05). The 11-deoxycortisol/cortisol ratio >2.2, <1.5, and <0.1 had 100% specificity to segregate C-11βOHD, NC-11βOHD, and control groups. Conclusion NC-11βOHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11βOHD.

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure.

The prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM. The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated. Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001). In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.