Objective: Prevalence of congenital hypothyroidism (CH) in Turkey at birth was reported to be as high as 1:650 in 2008-2010. Incidence rates of permanent and transient CH separately are unknown due to lack of follow-up data. We aimed to evaluate the impact of transient hypothyroidism on increasing incidence of CH and to determine the natural course and the clinical, biochemical, and imaging characteristics of transient CH.Methods: Baseline and follow-up data of the infants with CH detected at screening in six provinces in the Black Sea Region were analyzed retrospectively during a time period covering the years 2008-2010.Results: Among 138 cases (48% female), 16 (12%) showed transient hyperthyrotropinemia which resolved without intervention. Of the treated 122 cases, 63 (52%) had transient CH. While its frequency was 35% in 2008, it increased to 56% in 2009-2010, following a lowering of the thyroid stimulating hormone cutoff value. The frequency was higher in inland provinces than in coast (67% vs. 43%; p=0.01).Clinical characteristics of permanent and transient cases were similar except female-to-male sex ratios (1.5:1 vs. 0.6:1; p=0.02). L-thyroxine was discontinued in 70% of transient cases before 3 years of age at a median age of 19 (2-36) months. The only indication for early discontinuation of treatment was a low L-thyroxine dose, which was 1.25±0.27 µg/kg/day at withdrawal time.Conclusion: Our regional follow-up data showed that more than half of newborns with primary CH had transient thyroid dysfunction. In the majority of cases, discrimination between transient and permanent CH can be made before age 3 years, as indicated by cessation of L-thyroxine treatment.

Context The clinical effects of classical 3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency are insufficiently defined due to a limited number of published cases. Objective To evaluate an integrated steroid metabolome and the short- and long-term clinical features of 3βHSD2 deficiency. Design Multicenter, cross-sectional study. Setting Nine tertiary pediatric endocrinology clinics across Turkey. Patients Children with clinical diagnosis of 3βHSD2 deficiency. Main Outcome Measures Clinical manifestations, genotype-phenotype-metabolomic relations. A structured questionnaire was used to evaluate the data of patients with clinical 3βHSD2 deficiency. Genetic analysis of HSD3B2 was performed using Sanger sequencing. Novel HSD3B2 mutations were studied in vitro. Nineteen plasma adrenal steroids were measured using LC-MS/MS. Results Eleven homozygous HSD3B2 mutations (6 novel) were identified in 31 children (19 male/12 female; mean age: 6.6 ± 5.1 yrs). The patients with homozygous pathogenic HSD3B2 missense variants of > 5% of wild type 3βHSD2 activity in vitro had a non-salt–losing clinical phenotype. Ambiguous genitalia was an invariable feature of all genetic males, whereas only 1 of 12 female patients presented with virilized genitalia. Premature pubarche was observed in 78% of patients. In adolescence, menstrual irregularities and polycystic ovaries in females and adrenal rest tumors and gonadal failure in males were observed. Conclusions Genetically-documented 3βHSD2 deficiency includes salt-losing and non-salt–losing clinical phenotypes. Spared mineralocorticoid function and unvirilized genitalia in females may lead to misdiagnosis and underestimation of the frequency of 3βHSD2 deficiency. High baseline 17OHPreg to cortisol ratio and low 11-oxyandrogen concentrations by LC-MS/MS unequivocally identifies patients with 3βHSD2 deficiency.

The VTQ and VTIQ values reveal high-grade histopathologic fibrosis and have high success rates when distinguishing high- from low-grade fibrosis. However, they have limited success rates when differentiating low-grade fibrosis from normal liver tissue.

Background Although the relationship between circadian rhythm parameters and obesity in children and adolescents is recognized, there are few studies on this topic. The concept of sleep-corrected social jetlag (SJLsc) has been formulated recently, but its relationship with childhood obesity has not yet been established. Therefore, we thought that SJL might play an important role in the etiology of obesity. Accordingly, we aimed to compare circadian rhythm parameters between obese and normal-weight children and adolescents. Methods Seventy-nine obese and eighty-two normal-weight children and adolescents aged between 8 and 17 years participated in this case-control study, which took place in the Mardin province of Turkey. Data were collected with a sociodemographic information form, the Childhood Chronotype Questionnaire, and anthropometric measurements. Results The average ages of the obese participants and controls were 12.3 ± 2.3 and 12.4 ± 2.2 years, respectively. Obese young people had greater evening preference, longer sleep debt duration, SJL duration and SJLsc duration, and higher Morningness–Eveningness Scale (MeScale) scores; and shorter mean sleep duration (p<0.005). In regression analyses, BMI z scores were significantly correlated with all circadian rhythm parameters, except SJLsc duration, while WC z scores were significantly correlated with all circadian rhythm parameters, except mean sleep duration. After adjustment, the high MeScale scores (OR: 1.142, p<0.05) and the presence of psychiatric disorder in the mother (OR: 15.075, p<0.05) were associated with obesity. Conclusions Circadian rhythm parameters can play an important role in the etiology of obesity. Future studies with larger samples and fewer confounding factors are needed to clarify the etiological factors.

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (r s =0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis.

Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the mono-fluoromethyl unit and the C(sp3)–O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC–C→σ*C–F and σC–H→σ*C–O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.

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.