Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures.

Objective: Premature thelarche (PT) is defined as isolated breast development without secondary sex characteristics in girls below the age of eight. We aimed to determine whether the level of kisspeptin, which plays a role in the release of gonadotropins, is associated with PT.
Methods: The patient group included children with PT aged 3-8 years (n=20) and the control group included healthy children in the same age range (n=20). Height standard deviation scores (HSDSs), bone maturation and growth velocity were evaluated in the two groups. Basal follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), and sex hormone-binding globulin (SHBG) levels were also measured in the two groups by immunochemiluminometric assay (ICMA). A gonadotropin-releasing hormone (GnRH) test was also conducted in the patient group and the peak levels of FSH and LH were determined. Kisspeptin levels were measured using enzyme immunoassay (EIA).
Results: No differences were found between the groups in terms of age, HSDS, annual growth rate and bone age. While the plasma basal FSH, LH and E2 levels in the patient and control groups did not show statistically significant differences, PRL levels were higher in the patient group (p<0.05). Peak LH response to GnRH test was at the prepubertal level (<5 ng/mL) in patients with PT. In the patient group, kisspeptin levels were significantly higher compared to the levels in the control group (2.96±1.21 ng/dL vs. 1.19±0.41 ng/dL; p<0.05), and kisspeptin levels showed a significant correlation with PRL, FSH, LH, and E2 levels (p<0.05).
Conclusions: In this study, plasma kisspeptin levels were found to be higher in patients with PT and to show a positive correlation with increased PRL levels. Kisspeptin is one of the neuropeptides that plays a role in the onset of puberty. Our results support the hypothesis that PT may result from the temporary activation of central stimulants.

Objective: To investigate the role of interleukin-6 (IL-6) and C-reactive protein (CRP) in non-thyroidal illness (NTI) in premature infants.
Methods: Serum levels of IL-6 and CRP, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), total triiodothyronine (T3), and free T3 (fT3) were determined at the 1st, 2nd and 4th weeks of postnatal life in 148 premature infants born before 33 weeks of gestation.
Results: At the 1st week, serum T3 was negatively correlated with IL-6 (r= -0.33, p= 0.001) and CRP (r= -0.17, p= 0.03). Serum T3 was negatively and more strongly correlated with IL-6 (r= -0.49, p= 0.001) and CRP (r=- 0.33, p= 0.03) at the 2nd week, at which time sepsis frequency and low T3 rates were the highest. At the 4th week, mortality rate was higher among infants with lower T3 levels.
Conclusions: High IL-6 and CRP values related to neonatal sepsis might have a significant role in the pathogenesis of NTI in premature infants.

Objective: Developmental defects of the thyroid gland are the most frequent causes of permanent congenital hypothyroidism. This study aimed to investigate the epidemiological features of patients with thyroid dysgenesis (TD).
Methods: Medical records of 234 patients with TD followed between the years 2008 and 2010 were evaluated retrospectively. Diagnosis was made by ultrasonography.
Results: Of 234 patients, 120 (51.3%) were male and 114 (48.7%) were female. Male to female ratio was 1.08 and there were no significant differences in epidemiologic and clinical findings between girls and boys. One hundred eighty-three patients (78.2%) were diagnosed as hypoplasia, 35 (14.9%) as thyroid agenesis, 4 as ectopic thyroid gland and 12 as hemiagenesis. The mean maternal age of the group was 28.9±0.4 years (range 18 to 45 years), which is significantly higher than the recently reported mean maternal ages for Turkish women.
Conclusions: Advanced maternal age was more prevalent in patients with TD. Our clinical and epidemiologic findings suggested no evidence of sexual dimorphism.

Objective: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism.
Methods: 40 pubertal adolescents (20 females, 20 males; age range: 9-17 years) with exogenous obesity and 20 age- and sex-matched healthy adolescents (10 females, 10 males) were enrolled in the study. Oral glucose tolerance test (OGTT) was performed in the obese group. Serum glucose, insulin and visfatin levels were analyzed in the fasting state in the controls and at 0, 60 and 120 minutes during the OGTT in the obese group.
Results: The obese group had higher serum visfatin levels than the control group [11.6 (3.3-26) ng/mL vs. 7.5 (3.3-10.5) ng/mL, p<0.001]. Visfatin levels were correlated positively with body mass index, waist/hip ratio, insulin, and homeostasis model assessment for insulin resistance and negatively with glucose/insulin ratio in the combined group (obese subjects plus controls). Visfatin levels were essentially similar in obese subjects with and without insulin resistance (p>0.05). Serum visfatin levels did not change at 60 and 120 minutes of the OGTT compared to the baseline levels (p>0.05).
Conclusions: Serum visfatin levels are elevated in obese adolescents and do not change with acute changes in glucose metabolism. Visfatin levels are related with adiposity and glucose metabolism parameters. However, the role and contribution of adiposity and glucose metabolism to the circulating visfatin levels in obese patients remain to be explored.

Objective: This study aims to determine the relationship between the duration of persistent poor glycemic control in type 1 diabetes mellitus (T1DM) children and the likelihood of subsequent improvement.
Met­hods: A retrospective cohort study was conducted on T1DM patients aged 6-18 years, followed for at least six visits at Children’s National Medical Center (Washington, DC) with at least one hemoglobin A1c (HbA1c) ?10% after the first year since the initial visit (n=151). Medical records of patients with subsequently improved glycemic control were reviewed (n=39).
Re­sults: Patients aged 12-18 years, females, and Medicaid patients were twice as likely to be in persistently poor control as patients aged 6-11 years, males, and privately insured patients, respectively. Each additional visit with HbA1c ?10% and one percentage point increase in the mean HbA1c reduced the likelihood of subsequent improvement by 20% and 50%, respectively. Of the 39 patients with improved control, only 5 (13%) sustained their improvement for ?2 years. Multiple contributing factors for improved control were identified, but no one factor explained improved control in >25% of patients.
Conc­lu­si­on: This study suggests that the longer the duration of poor control, the more difficult it is to reverse the underlying factors of poor diabetes management. Strategies to improve regular clinic attendance along with reinforcement of changes which resulted in improved control are critical. Adolescents, females, and Medicaid patients in particular should be targeted for sustained intervention.

Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form of hypophosphatemia with hyperphosphaturia, hypercalciuria, and hypercalcemia. In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter. Our objective was to define the clinical course of these cases in a family with HHRH and to screen for SLC34A3 gene in order to determine whether these mutations are responsible for HHRH.
Methods: After clinical and biochemical evaluations, the entire SLC34A3 gene was screened using PCR amplification followed by direct sequencing technique. In this paper, we describe a new kindred with HHRH and a case of progressive and complicated HHRH presenting at age 27 years.
Results: We found 101-bp deletion in intron 9 of the SLC34A3 gene. The index patient was homozygous for this mutation which has been previously reported in a Caucasian population. This is the first report for presence of SLC34A3 intron 9 deletion in an Iranian population.
Conclusions: These data showed that HHRH can be easily missed or underdiagnosed. Genetic evaluation of patients with familial hypercalciuria, hypophosphatemia and nephrolithiasis is needed for further information on the prevalence and management of this rare disorder.

Objective: Early diagnosis and treatment of testicular adrenal rest tumors (TART) is important for gonadal functions and fertility protection in boys with congenital adrenal hyperplasia (CAH). In this descriptive study, we investigated the prevalence of TART in boys with 21-hydroxylase deficient (21OHD) CAH followed in our pediatric endocrine clinic.
Methods: The study group consisted of 14 male patients with a mean age of 9.6±5.1 (range: 0.8-18.3) years. Six (42.9%) of the 14 patients were diagnosed as having salt-wasting type (SW) and eight (57.1%) patients - as having the simple virilizing (SV) form of 21OHD. Mean age at diagnosis was 2.9±2.7 (range: 0.03-6.3) years. Two different radiologists performed scrotal ultrasonography. Chronological age, bone age, and anthropometric measurements were evaluated. Serum adrenocorticotropic hormone (ACTH), 17-alpha-hydroxyprogesterone (17OHP) and androstenedione levels were also evaluated in all patients during the follow-up period.
Results: Scrotal ultrasonography revealed bilateral TART in two patients (14.3%) and testicular microlithiasis (TM) in four patients (28.6%). One patient had both TART and TM bilaterally. During the follow-up period, the mean serum adrenocorticotropic hormone, 17OHP and androstenedione levels in the total group of patients were 130.0±179.1 pg/mL (21.7-726.5), 5.8±3.3 ng/mL (0.8-11.4) and 4.3±4.1 (0.2-11.0) ng/mL, respectively.
Conclusions: Microlithiasis or TART may be frequently encountered during the follow-up of patients with CAH. In order to prevent late complications including infertility, we suggest that ultrasonographic evaluations be performed yearly in all male CAH patients.

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disordercharacterized by early-onset diabetes, spondyloepiphyseal dysplasia,tendency to skeletal fractures secondary to osteopenia, and growthretardation. Mutations in the eukaryotic translation initiation factor 2?kinase (EIF2AK3)gene are responsible for this disorder. Here, wedescribe a boy with neonatal diabetes, diagnosed at 2 months of age,who developed severe growth retardation and a skeletal fracture duringthe follow-up period. The patient’s skeletal X-ray revealed findings ofskeletal dysplasia. A clinical diagnosis of WRS was confirmed by theidentification of a novel homozygous nonsense mutation (R491X) in exon9 of the EIF2AK3 gene. The aim of this report is to raise the awarenessfor Wolcott-Rallison syndrome in cases presenting with isolatedneonatal diabetes. This patient demonstrates that the other findings ofthis syndrome might be obscured by a diagnosis of isolated neonataldiabetes.

Maturity-onset diabetes of the young type 3 (MODY3) is caused by heterozygous mutation in the HNF1A gene. Liver adenomatosis has been reported in MODY3 patients. The patient reported in this paper is a Japanese girl who first developed hepatomegaly, fatty liver, and hepatic dysfunction at age 5 years. Liver biopsy demonstrated steatosis and degeneration of hepatocytes. At that time, blood glucose and HbA1c levels were within normal ranges. Elevated HbA1c was noticed 4 years later, but islet cell and glutamic acid decarboxylase antibodies were not detected in the serum. Therefore, MODY3 was suspected and subsequent analysis of the HNF1A gene identified a heterozygous germline splice donor-site mutation in intron 9. MODY3 patients should be screened by non-invasive liver imaging, and careful follow-up of liver disease should be performed.

Permanent neonatal diabetes mellitus (PNDM) is a rare condition presenting before six months of age. Mutations in the genes encoding the ATP-sensitive potassium (KATP) channel are the most common causes. Sulfonylurea (SU) therapy leads to dramatic improvement in diabetes control and quality of life in most patients who carry these mutations. Here, we report the long-term follow-up results of two siblings with PNDM who were treated with insulin until ABCC8 gene mutation was identified, and were successfully transferred to oral SU therapy. After 3.5 years of follow-up on SU, one patient had a very good response, while the other one had a poor response. Bad compliance to diet was thought to be the most probable reason for poor glycemic control in this patient. In conclusion, molecular genetic diagnosis in all patients with PNDM is recommended. Compliance to treatment should be an important aspect of the follow-up of these patients.

Radioactive iodine (RAI) is used effectively in the treatment of hyperthyroidism and thyroid cancer, but it is contraindicated during pregnancy. RAI treatment during pregnancy can lead to fetal hypothyroidism, mental retardation and increased malignancy risk in the infant. Pregnancy tests must be performed before treatment in all women of reproductive age. However, at times, RAI is being used before ruling out pregnancy.
We herein present a male newborn infant with congenital hypothyroidism whose mother was given a three-week course of methimazole therapy for her multiple hyperactive nodules and subsequently received 20 mCi RAI during the 12th week of her pregnancy. The patient was referred to our neonatology unit at age two weeks when his thyrotropin (TSH) level was reported to be high in the neonatal screening test. Physical examination was normal. Laboratory investigations revealed hypothyroidism (free triiodothyronine 1.55 pg/mL, free thyroxine 2.9 pg/mL, TSH 452 mU/L, thyroglobulin 20.1 ng/mL). The thyroid gland could not be visualized by ultrasonography. L-thyroxine treatment was initiated.