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

To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship.Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses ofA mutation in MODY genes was identified in 12 (29%) of the cases.The results of this study showed that mutations in the

Purpose: We aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH. Methods: This retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by “National Newborn Screening Program” (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET). Results: Of the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34–38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750. Conclusion: According to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

Context There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. Objective This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. Methods Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography–mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. Results A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. Conclusion Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

Hypophosphatemic rickets (HR) is a rare renal phosphate wasting disorder commonly related to X-linked form, caused by PHEX mutations and its treatment and follow-up is challenging due to imperfect treatment options. Here we presented nationwide data on HR with initial and follow-up data on the patients. From 24 centers, 166 patients were included in the study data. Genetic analysis (n:75) showed PHEX mutation in 80% patients. The mean follow-up period of the patients was 6.7± 2.4 years. During first 3 year treatment (n:91), mild increase in phosphate , decrease in ALP and, elevation in PTH levels had been detected. The height SDS were -2.38, -2.77, -2.72, -2.47 at intitial, 1st, 2nd and 3rd year of treatment, respectively (p>0.05). In follow-up: 36% of the patients showed complete or significant improvement in leg deformities, and, these patients had similar phosphate levels at presentation with better levels in 1st and 2nd years of treatment, even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis, the patients showed no difference in biochemical differences in presentation and follow-up, but 3rd year PTH was higher, however, higher treatment dose of phosphate and calcitriol has been detected in nephrocalcinosis group. HR treatment and follow-up is challenging and our results showed higher treatment doses leading nephrocalcinosis without any change in serum levels, suggesting given higher doses lead higher phoshaturia probably through the stimulation FGF23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.

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 II 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 <0.000). 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.