High frequency of transient congenital hypothyroidism among infants referred for suspected congenital hypothyroidism from the Turkish National screening program: thyroxine dose may guide the prediction of transients.

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.

THYROID DYSFUNCTION CAUSED BY MATERNAL AUTOIMMUNE THYROIDITIS: TWO DIFFERENT CLINICAL PICTURES IN TWO SIBLINGS.

Objectives: Maternal antibodies in cases of chronic autoimmune thyroiditis may be transferred to the baby via the transplacental route, leading to transient hyperthyroidism or hypothyroidism. The development of hyperthyroidism in one sibling and hypothyroidism in the other, however, is an extremely rare condition. We present two siblings, one with transient neonatal hyperthyroidism and the other with transient neonatal hypothyroidism, born to a euthyroid mother who was being treated for Hashimoto's thyroiditis. Case Presentation: Case 1: A term male baby was evaluated due to tachycardia, high fT4 and low TSH. Following a diagnosis of Neonatal thyrotoxicosis, the patient was started on methimazole and propranolol treatments. The doses were gradually reduced and methimazole was stopped in the 5th month of treatment. Case 2: A male baby was referred with elevated TSH identified in the neonatal screening program, with TSH >100 mIU/L and fT4 7.5 pmol/l (N: 12-22) found in a venous blood sample. The patient was started on 50 µg/day LT4, which was gradually decreased and stopped when the baby was 5.5 months old. Conclusion: It should be kept in mind that antibodies may change character in mothers with autoimmune thyroiditis, and may cause different clinical pictures in babies in different pregnancies.

PUBERTAL VIRILIZATION IN AN ADOLESCENT WITH 46, XY DISORDER OF SEXUAL DEVELOPMENT: A NOVEL MUTATION IN NR5A1 GENE.

Background: NR5A1 [Steroidogenic factor 1 (SF1)] is a nuclear receptor that is essential for the development of gonads and adrenal glands as well as the establishment of steroidogenesis in these organs. The clinical findings of the mutations of NR5A1 gene in 46, XY individuals are variable. Virilization at puberty can be seen in some of the 46, XY children who have a female phenotype and are raised as female.A girl aged 13 years and 10 months old was brought by the family for deepening of her voice. On physical examination, her breast development was Tanner stage 2, axillary hair (+) and pubic hair was Tanner stage 4. She had labioscrotal fusion and 4.4 cm phallus (External Masculinisation Score was 6). Hypergonadotropic hypogonadism, low AMH and high testosterone levels were detected in laboratory tests. Uterus was not visualized in pelvic ultrasonography. Karyotype analysis was reported as 46, XY. Sequence analysis of the NR5A1 gene revealed a novel heterozygote c.1075_1089del (p.Leu359_Leu363del) variant. The patient was raised as a female and oestrogen replacement was started following gonadectomy. Conclusion: It should be kept in mind that virilization may develop at puberty in individuals with 46, XY disorder of sexual development due to NR5A1 mutation.

A novel mutation in steroidogenic factor (SF1/NR5A1) gene in a patient with 46 XY DSD without adrenal insufficiency.

Steroidogenic factor-1 (SF-1), also known as nuclear receptor subfamily 5 group A member 1 (NR5A1), is a member of orphan receptor subfamily and located on chromosome 9 (9q33). In 46, XY individuals with mutation of SF-1 gene, adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus, infertility can occur from severe to mild. We report a case of a 20-day-old male who is admitted to our clinic due to ambiguous genitalia. In this report, we describe a novel heterozygous c.814A > C (p. T272P) NR5A1 mutation in a patient with 46, XY DSD without adrenal insufficiency. We describe a novel missense mutation c.814A > C (p. T272P) in NR5A1 gene which had not previously been reported. Also this report highlights that the potential diagnostic utility of next-generation sequencing is an effective strategy versus Sanger sequencing to identify genetic mosaicism in clinical practice.

Association Between Vitamin D Receptor Polymorphism and Familial Mediterranean Fever Disease in Turkish Children.

Familial Mediterranean fever (FMF) is an autosomal recessive, inherited autoinflammatory disease characterized by recurrent, self-limited attacks of fever, and inflammation of serosal surfaces. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of children with FMF. We investigated VDR FokI (rs10735810), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms in 50 children with FMF and 150 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism. There was no significant difference between patients and controls for VDR FokI, TaqI, BsmI, and ApaI genotypes and alleles (p > 0.05). Results need to be supported by further investigations that define haplotype patterns for VDR gene polymorphisms in a larger group and different ethnic groups of FMF patients.

Serum nesfatin-1 and leptin levels in non-obese girls with premature thelarche.

AIM: We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process. SUBJECTS-METHODS: Non-obese girls who presented with the complaint of early (2-8 years) and isolated breast development were included in the study. The control group consisted of age-matched healthy prepubertal girls. Auxological measurements were performed in all subjects. Gonadotropin-releasing hormone (GnRH) stimulation test and bone age assessment were conducted in subjects with early breast development. Girls with a bone age/chronologic age ratio <1.2 and a peak luteinizing hormone (LH) response to GnRH stimulation <5 mIU/L were included in the PT group. RESULTS: The study included 22 non-obese girls with PT and 24 healthy prepubertal controls. Body mass index (BMI), BMI-standard deviation score (SDS) and height SDS were similar between the groups (p > 0.05). Serum leptin and nesfatin-1 levels were found significantly higher in the PT group compared to controls (p < 0.05). No correlation was detected between nesfatin-1 and basal LH, basal follicle stimulating hormone (FSH), stimulated peak LH, peak FSH, leptin levels and anthropometric parameters in the PT group (p > 0.05). CONCLUSION: Results of the present study showed that serum nesfatin-1 and leptin levels are significantly higher in girls with PT than in prepubertal controls. This finding suggests that similar to leptin, nesfatin-1 may also have a central or peripheral role in the initiation of pubertal process and may be related to PT pathogenesis.

Endocrine cancer syndromes: an update.

Endocrine neoplasms comprise a variety of benign and malign tumors that arise from the endocrine glands or neuroendocrine tissues. Although most endocrine neoplasms are sporadic, others are secondary to mutations of many known tumor-predisposing genes. Endocrine cancer syndromes, including Multiple Endocrine Neoplasia type 1 (MEN1), Multiple Endocrine Neoplasia type 2 (MEN2A and MEN2B), Multiple Endocrine Neoplasia type 4 (MEN4) syndromes, and inherited syndromes with different endocrine neoplasms (von Hippel-Lindau disease, Carney complex, Neurofibromatosis type 1, others) are heterogeneous group of cancer susceptibility syndromes that affect one or more of the endocrine glands or neuroendocrine tissues. Genetic studies and researches as well as technological possibilities allowed for detection of new endocrine cancer syndromes and genes leading to tumor susceptibility. In addition, early detection of children at risk for endocrine cancer syndromes using molecular analysis methods provided opportunity to regular monitoring of potential malignancies and timely intervention for these cases (e.g. early prophylactic thyroidectomy in MEN2). This review will describe the clinical, genetic, diagnostic and therapeutic options for endocrine cancer syndromes based on the current literature data.

Low omentin-1 levels are related with clinical and metabolic parameters in obese children.

This is the first clinical study evaluating the relation of serum omentin 1 levels with anthropometric and metabolic parameters in obese children with a particular interest to identify the possible role of omentin 1 in childhood obesity and related metabolic disturbances.The study included obese children with a body mass index (BMI)>95th percentile and healthy children with a BMI<85th percentile. The healthy and obese subjects had similar age and gender distribution. Glucose, insulin, lipid profile, and omentin 1 levels were measured to evaluate the metabolic parameters.49 obese children who applied to our department with complaint of weight gain and 30 healthy age and sex matched subjects were enrolled. In obese children BMI, body mass index-standard deviation score (BMI-SDS), systolic blood pressure (SBP), diastolic blood pressure (DBP), mid-arm circumference (MAC), triceps skin fold (TSF), waist circumference (WC), homeostasis model assessment-insulin resistance (HOMA-IR), serum insulin, and triglyceride levels were higher whereas omentin-1 levels were lower than control subjects (p<0.05). In the obese group, omentin 1 level was negatively correlated with BMI, insulin, HOMA-IR, and WC, while no significant correlation was observed with other parameters (p>0.05). Additionally, although statistically insignificant, patients with IR (n=31) had lower omentin-1 levels compared to obese children without IR (n=18).Our data indicates that serum omentin 1 levels are i) lower in obese children and ii) negatively correlated with BMI, WC, HOMA-IR and insulin levels suggesting that omentin 1 might be a biomarker for metabolic dysfunction also in childhood and adolescence. Lower omentin 1 levels tended to be associated with insulin resistance however this association failed to reach statistical significance. Further studies in larger populations are needed to better-define the relation of omentin 1 and insulin resistance in obese children.

Transición parasitaria a Blastocystis hominis en niños de la zona centro del estado de Guerrero, México / Parasitic transition to Blastocystis hominis in children from center zone of Guerrero state, Mexico

Blastocystis hominis es un organismo emergente cuya prevalencia se ha incrementado en los últimos años. La frecuencia en México va de 4,0 por ciento a 62 por ciento, sin reportes previos en el estado de Guerrero. La población estudiada fueron tres localidades del estado de Guerrero: Chilpancingo, Petaquilla y Tixtla en un total de 1.138 niños preescolares y escolares, de ambos sexos. Mediante tres técnicas coproparasitóscopicas (CPS): examen directo, concentración por flotación de Faust y cultivo de Barret, se detectaron un total de 38 por ciento de niños parasitados y B. hominis ocupó el primer lugar con el 61 por ciento de los CPS positivos. El 90 por ciento de los casos fueron parasitosis única. El 58 por ciento de los niños aparentemente sanos y con B. hominis declararon tener algún síntoma gastrointestinal. La asociación de B. hominis con dolor abdominal y beber agua de la llave tuvo diferencia significativa. Proponemos una transición parasitaria a B. hominis como principal parásito del hombre, como resultado de las medidas de control para las parasitosis intestinales.

Blastocystis hominis is an enteric emergen organism found in human it's prevalence has been increasing in the lasts years. The frequency in Mexico is from 4.0 percent to 62 percent, without reports in the Guerrero state. The aim of this study was to inform the parasitic transition to B. hominis in the Central Zone of Guerrero state. The population in this study were three communities of Guerrero state: Chilpancingo, Petaquilla and Tixtla in a total of 1,138 preschools and schools children of both sexs. Three parasitological tests were used for detection of the parasite in stool specimens: micrscopy of direct smears, concentration and flotation technique and serum-solution saline culture. Global prevalence of parasites was of 38 percent and B. hominis was the principal parasite with 61 percent on the positive tests. The 90 percent were only B. hominis and 10 percent with others parasites. A total of 58 percent of the children healthy with B. hominis declarated have gastrointestinal symptoms. The association ofB. hominis with abdominal pain and drinking taste water had significant difference. We propuse a parasitic transition to B. hominis as principal human parasite, this can be the result of man-made intervention in the intestinal parasitosis control.