Congenital adrenal hyperplasia (CAH) is classified as classical CAH and non-classical CAH (NCCAH). In the classical type, the most severe form comprises both salt-wasting and simple virilizing forms. In the non-classical form, diagnosis can be more confusing because the patient may remain asymptomatic or the condition may be associated with signs of androgen excess in the postnatal period or in the later stages of life. This review paper will include information on clinical findings, symptoms, diagnostic approaches, and treatment modules of NCCAH.

Objective: Thyroid abnormalities are common in obese children. The aim of the present study was to examine the prevalence of subclinical hypothyroidism (SH) and to determine how circulating thyroid hormone concentrations correlate with anthropometrics in Danish lean and obese children and adolescents.
Methods: In this cross-sectional study, we included 3006 children and adolescents, aged 6-18 years, from the Registry of the Danish Childhood Obesity Biobank. The overweight/obese group (n=1796) consisted of study participants with a body mass index (BMI) standard deviation score (SDS) ?1.28. The control group (n=1210) comprised lean children with a BMI SDS <1.28. All participants were characterized by anthropometrics (weight, height, and waist circumference) and fasting serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine (fT4) at baseline.
Results: The prevalence of SH was higher among overweight/obese compared to lean study participants (10.4% vs. 6.4%, p=0.0001). In the overweight/obese group, fasting serum TSH concentrations were associated positively with BMI SDS (p<0.0001) and waist-height ratio (WHtR) (p<0.0001) independent of age, sex, and pubertal developmental stage, whereas fasting serum fT4 concentrations were associated positively only with WHtR. The odds ratio of exhibiting SH was 1.8 when being overweight/obese compared with lean (p=0.0007) and 1.8 when presenting with a WHtR >0.5 (p=0.0003).
Conclusion: The prevalence of SH was higher among overweight/obese study participants. The positive correlations of circulating TSH and fT4 with WHtR suggest that central obesity, independent of the overall degree of obesity, augments the risk of concurrent thyroid abnormalities in children and adolescents with obesity.

Objective: Limited information is available about the use of neck circumference (NC) to assess obesity in preschool children. This study aims to provide NC percentiles and determine the cut-off levels of NC as a measure to assess obesity in preschool children.
Methods: The data were obtained from the Anthropometry of Turkish Children aged 0-6 years (ATCA-06) study database. A total of 21 family health centers were chosen and children aged 2-6 years old from all socioeconomic levels were randomly selected from the lists of district midwives; 1766 children (874 male and 892 female; 88.3% of sample size) were included in the study. The smoothed centile curves of NC were constructed by the LMS method. Receiver operating characteristic (ROC) analysis was performed to calculate cut-off points for NC using body mass index ?95th percentile.
Results: Mean NC was greater in males than females. Cut-off values for obesity were found to be statistically significant in both genders other than 3 years old boys. The NC percentiles of Turkish preschool children were slightly greater than those of other European preschool children in both genders. This difference disappeared around the adiposity rebound period. The 97th percentile values for Turkish preschool children continue to be greater in both genders.
Conclusion: NC may be useful to define obesity in preschool children. Since ethnic and various other factors may have a role in incidence of obesity, local reference data are important in assessment of obesity.

Objective: ADAMTS-1 is a matrix metalloproteinase which cleaves versican in the cumulus oocyte complex under the effect of luteinizing hormone surge in the periovulatory period. Altered levels may have a role in the pathogenesis of polycystic ovary syndrome (PCOS). We aimed to determine the serum versican and ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif-1) levels in PCOS patients and compare the results with healthy controls.
Methods: Thirty-eight patients with PCOS and forty healthy controls aged between 15 and 22 years were included in the study. They were sampled according to their basal hormone, serum versican, and ADAMTS-1 levels. Serum versican and ADAMTS-1 levels were measured by enzyme-linked immunosorbent assay. A multivariate logistic regression model was used to identify the independent risk factors of PCOS.
Results: Serum versican levels were significantly decreased in the PCOS group when compared with the controls. The best versican cut-off value for PCOS was calculated to be 33.65 with 76.74% sensitivity and 52.94% specificity. Serum versican levels, homeostasis model assessment of insulin resistance index, a Ferriman-Gallwey score higher than 8, and oligomenorrhea were the strongest predictors of PCOS. Serum versican levels were significantly decreased in PCOS patients. Besides, serum ADAMTS-1 and versican levels were significantly and positively correlated with each other.
Conclusion: Serum versican levels were significantly decreased in patients with PCOS. This suggests a possible role of versican in ovulatory dysfunction and in the pathogenesis of PCOS.

Objective: To investigate the relationship between zonulin levels and clinical and laboratory parameters of childhood obesity.
Methods: The study included obese children with a body mass index (BMI) >95th percentile and healthy children who were of similar age and gender distribution. Clinical (BMI, waist circumferences, mid-arm circumference, triceps skinfold, percentage of body fat, systolic blood pressure, diastolic blood pressure) and biochemical (glucose, insulin, lipid levels, thyroid function tests, cortisol, zonulin and leptin levels) parameters were measured.
Results: A total of 43 obese subjects (23 males, mean age: 11.1±3.1 years) and 37 healthy subjects (18 males, mean age: 11.5±3.5 years) were included in this study. Obese children had significantly higher insulin, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), zonulin and leptin levels than healthy children (p<0.05), while glucose levels were not different (p>0.05). Comparison of the obese children with and without insulin resistance showed no statistically significant differences for zonulin levels (p>0.05). Zonulin levels were found to negatively correlate with HDL-C and positively correlate with leptin levels, after adjusting for age and BMI.
Conclusion: To the best of our knowledge, this is the first study investigating the relationship between circulating zonulin level (as a marker of intestinal permeability) and insulin resistance and leptin (as markers of metabolic disturbances associated with obesity) in childhood obesity. The results showed that zonulin was significantly higher in obese children when compared to healthy children, a finding indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances.

Objective: To compare updated weight and height percentiles of 6-17-year-old children from all socio-economic levels in Kayseri with previous local references and other national/international data.
Methods: The second study “Determination of Anthropometric Measurements of Turkish Children and Adolescents study (DAMTCA II)” was conducted in Kayseri, between October 2007 and April 2008. Weight and height measurements from 4321 (1926 boys, 2395 girls) school children aged between 6 to 17 years were included in this cross-sectional study. Using these data, weight and height percentile curves were produced with generalized additive models for location, scale and shape (GAMLSS) and compared with the most recent references.
Results: Smoothed percentile curves including the 3rd, 5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, 95th, and 97th percentiles were obtained for boys and girls. These results were compared with DAMTCA I study and with two national (Ýstanbul and Ankara) and international data from Asia and from Europe.
Conclusion: This study provides updated weight and height references for Turkish school children aged between 6 and 17 years residing in Kayseri.

Objective: Otitis media with effusion (OME) is a condition in which fluid is retained in the middle ear cavity. The association between endocrine disorders and OME has not yet been determined. This study aimed to investigate the presence of OME in children diagnosed with an endocrine disease and the relationship between these two conditions.
Methods: The study was conducted on 918 pediatric patients (440 boys, 478 girls; mean age: 8.40, range 3-15 years) and 158 healthy controls (76 boys, 79 girls; mean age: 8.31, range 3-15 years). All children underwent an ear examination and a tympanometry performed by an otorhinolaryngologist. Tympanometry results were used to diagnose OME.
Results: OME was detected in 205 (22.3%) of 918 patients and in 19 (12.0%) of 158 subjects in the control group. The difference in frequency of OME between the two groups was statistically significant (p=0.003).
Conclusion: The results of the study reveal that there may be a tendency towards the occurrence of OME in pediatric endocrinology patients.

Objective: To investigate the clinical and molecular features of congenital generalized lipodystrophy (CGL) in three Chinese patients with various typical manifestations.
Methods: Data on clinical symptoms, results of laboratory analyses, and previous treatments in three Chinese patients were collected by a retrospective review of medical records. All coding regions and adjacent exon–intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced.
Results: Generalized lipodystrophy, acanthosis nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly were features in all three patients. Patient 1 developed diabetes mellitus at the early age of 2 months and he was the youngest CGL patient reported with overt diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months. All of the patients were found to have mutations in the BSCL2 gene, but none of these was a novel mutation. We did not find any AGPAT2 mutation in our patients.
Conclusion: All of our patients exhibited characteristic features of CGL due to mutations in the BSCL2 gene.

Objective: The aim of the present study was to document ovarian cyst frequency and characteristics as well as distribution of these parameters with respect to age in children and adolescents.
Methods: We retrospectively analyzed the medical records of 1009 girls between the ages of 5-18 years who presented to our pediatric emergency department (PED) with pelvic pain and therefore underwent pelvic ultrasound examination between June 2011 and May 2014.
Results: In total, 132 of 1009 girls (13.1%) were identified as having ovarian cysts ?1 cm in diameter. The frequency of ovarian cysts was found to be 1.8% (6/337) in children aged 5-9 years and 18.8% (126/672) in those aged 10-18 years. All the cysts detected in children aged 5-9 years were small (<3 cm) and simple with age-specific frequencies ranging between 1.5-2.7%. With the onset of adolescence, ovarian cyst frequency started to increase with age and ranged between 3.8-31.3% throughout adolescence. Age of peak ovarian cyst frequency was 15 years with a rate of 31.3%. Large ovarian cysts (>5 cm) were identified in 19 adolescents (15.1%) with most occurring during middle adolescence. Of the 19 adolescents, five were found to have cyst-related significant ovarian pathologies including cystadenoma (n=3) and ovarian torsion (n=2).
Conclusion: In children aged 5-9 years, ovarian cysts were infrequent and small (<3 cm). Peak ovarian cyst frequency was detected at the age of 15 years. All patients diagnosed with cyst-related significant ovarian pathologies were adolescents having a cyst >5 cm in diameter with a complex appearance in most.

Objective: Stosstherapy has been used since early 19th century for treating nutritional rickets. However, there are no clear cut guidelines for the biochemical monitoring of this treatment. Repeated blood tests at short intervals increase the cost of therapy and noncompliance.
Methods: A prospective study was conducted on 191 cases of nutritional rickets below 10 years of age to evaluate the effectivity of stosstherapy. All cases were treated with a single intramuscular injection of vitamin D (600.000 IU) along with oral calcium (50 mg/kg) and vitamin D (400 IU per day) until radiological resolution. Dietary modifications and adequate sunlight exposure were also recommended.
Results: The mean age of presentation was 2 years 9 months. Mean sunlight exposure was 17 minutes/week with 90% having low sunlight exposure (<30 minutes/week). Prolonged breast feeding (>6 months) was found in 93.7% of the cases. With treatment, the clinical features started resolving by 1 month with complete resolution of most of the features over a period of 1 year. By 6 months, all the study subjects had complete radiological resolution. Serum levels of calcium and alkaline phosphatase (ALP) were restored by 6 months in most cases while phosphate and vitamin D levels normalized by 6 weeks.
Conclusion: Stosstherapy is a safe, cheap and effective method of treating nutritional rickets. Biochemical tests at initial presentation followed by vitamin D assay at 6 weeks and calcium, phosphate and ALP assays at 6 months is recommended in the monitoring of these patients. For regular monitoring, only ALP assay is recommended, provided one abstains from repeat injection of vitamin D based on high ALP levels.

Steroid 3-beta hydroxysteroid dehydrogenase type II (3ß-HSD2) deficiency is a rare autosomal recessive form of congenital adrenal hyperplasia (CAH). We report the genetic basis of 3ß-HSD2 deficiency arising from uniparental isodisomy (UPD) of chromosome 1. We describe a term undervirilized male whose newborn screen indicated borderline CAH. The patient presented on the 7th day of life in salt-wasting adrenal crisis. Steroid hormone testing revealed a complex pattern suggestive of 3ß-HSD deficiency. Chromosomal microarray and single nucleotide polymorphism analysis revealed complete UPD of chromosome 1. Sanger sequencing of HSD3B2 revealed a previously described missense mutation, c.424G>A (p.E142K) in homozygous state, thus confirming the diagnosis of 3ß-HSD2 deficiency. We provide evidence of the existence of an uncommon mechanism for HSD3B2 gene-related CAH arising from UPD of chromosome 1.

Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by multihormone resistance and an Albright hereditary osteodystrophy (AHO) phenotype. It is caused by heterozygous mutations in GNAS gene. Clinical and biochemical findings of a female PHP-Ia patient were evaluated from age of diagnosis (6.5 years) to 14.5 years of age. The patient had short stature, brachydactyly, and subcutaneous heterotopic ossifications. Serum calcium and phosphorus levels were normal, but parathyroid hormone levels were high. Based on the typical clinical findings of AHO phenotype and biochemical findings, she was diagnosed as having PHP-Ia. A novel heterozygous mutation (c.128T>C) was found in the GNAS gene. Follow-up examinations revealed resistance to thyroid-stimulating hormone and a bioinactive growth hormone. Clinicians should take into consideration PHP-Ia in patients referred with short stature, and patients with an AHO phenotype must be further evaluated for hormone resistance, GNAS gene mutation, Gs? activity. To our knowledge, this is the first case report describing bioinactive growth hormone in PHP-Ia.

Wolfram syndrome (WS) is an autosomal recessive disorder caused by mutations in WFS1 gene. The clinical features include diabetes insipidus, diabetes mellitus (DM), optic atrophy, deafness, and other variable clinical manifestations. In this paper, we present the clinical and genetic characteristics of 3 WS patients from 3 unrelated Turkish families. Clinical characteristics of the patients and the age of onset of symptoms were quite different in each pedigree. The first two cases developed all symptoms of the disease in their first decade of life. The heterozygous father of case 2 was symptomatic with bilateral deafness. The first ocular finding of one patient (patient 3) was bilateral cataract which was accompanying DM as a first feature of the syndrome. In this patient’s family, there were two members with features suggestive of WS. Previously known homozygous mutations, c.460+1G>A in intron 4 and c.1885C>T in exon 8, were identified in these cases. A novel homozygous c.2534T>A mutation was also detected in the exon 8 of WFS1 gene. Because of the rarity and heterogeneity of WS, detection of specific and nonspecific clinical signs including ocular findings and family history in non-autoimmune, insulinopenic diabetes cases should lead to a tentative diagnosis of WS. Genetic testing is required to confirm the diagnosis.

Testicular adrenal rest tumors (TART) occur frequently in adolescents and adults with 21-hydroxylase deficiency. There have been no reports of TART in children with 3ß-hydroxysteroid dehydrogenase deficiency (HSD3ß). Biopsy proven TART was diagnosed in a 31/12-year-old male patient and also in his 22-month-old sibling. Hormonal and anthropometric measurements were performed during glucocorticoid and fludrocortisone treatment. The mutational analysis was performed by direct DNA sequencing of the complete coding region of the HSD3ß2 gene. Initially, both siblings were treated with high doses of hydrocortisone and fludrocortisone. TART regressed with dexamethasone treatment in both patients. However, growth velocity decreased and weight gain increased in both patients. Dexamethasone was changed to high-dose hydrocortisone (>20 mg/m2/d). Sequencing analyses revealed a novel homozygous p.W355R (c.763 T>C) mutation at exon 4 of the HSD3ß2 gene in both siblings. These two patients are, to our knowledge, the first known cases of TARTs with a novel mutation in the HSD3ß2 gene detected during childhood. High-dose hydrocortisone treatment is more reliable for TART in children.

The Miller-McKusick-Malvaux (3M) syndrome is a rare autosomal disorder that can lead to short stature, dysmorphic features, and skeletal abnormalities with normal intelligence. A 16-month-old female patient had been referred to our clinic due to short stature. Case history revealed a birth weight of 1740 grams on the 39th week of gestation, with a birth length of 42 cm and no prior hereditary conditions of clinical significance in her family. On physical examination, her length was 67 cm [-3.6 standard deviation (SD) score], weight 7.2 kg (-2.9 SD score), and head circumference 42 cm (below 3rd percentile). She also had numerous characteristic physical features such as a triangular face, fleshy nose tip, a long philtrum, prominent mouth and lips, pointed chin, lumbar lordosis, and prominent heels. As her growth retardation had a prenatal onset and the physical examination results were suggestive of a characteristic profile, the diagnosis of 3M syndrome was strongly considered. Genetic assessment of the patient revealed a novel homozygous p.T425Nfs*40 mutation in the OBSL1 gene. It is recommended that physicians pay further attention to this condition in the differential diagnosis of children with severe short stature.