Intracranial tumors are the second most frequent malignancies in children and posterior fossa is a common location for these neoplasias during childhood. Recent advances in surgical techniques, radiotherapy and chemotherapy resulted in dramatic increase in the survival rates of these children, however they are still source of a significant morbidity and mortality. Endocrinological complications and late sequelae of childhood posterior fossa tumours are common among the survivors of these tumours and include growth retardation, hypothyroidism, pubertal disorders, gonadal dysfunction and osteopenia. These complications have significant impact on the quality of life of the survivors of childhood posterior fossa tumours. In this paper, the frequency, etiology, and management of these complications will be reviewed.

Objective: No evidence-based guideline has been published about optimal referral criteria and diagnostic work-up for tall stature in children. The aim of our study was to describe auxological and clinical characteristics of a cohort of children referred for tall stature, to identify potential candidates for adult height reduction, and to use these observations for developing a simple algorithm for diagnostic work-up and follow-up in clinical practice.
Methods: Data regarding family and medical history, auxological measurements, bone age development, physical examination, additional diagnostic work-up, and final diagnosis were collected from all children referred for tall stature, irrespective of their actual height standard deviation score (HSDS). Predicted adult height (PAH) was calculated in children above 10 years. Characteristics of patients with an indication for adult height reduction were determined.
Results: Hundred thirty-two children (43 boys) with a mean ± SD age of 10.9±3.2 (range 0.5-16.9) years were included in the study. Fifty percent of the referred children had an HSDS ?2.0 (n=66). Two pathological cases (1.5%) were found (HSDS 2.3 and 0.9). Tall children without pathology were diagnosed as idiopathic tall, further classified as familial tall stature (80%), constitutional advancement of growth (5%), or unexplained non-familial tall stature (15%). Of the 74 children in whom PAH was calculated, epiphysiodesis was considered in six (8%) and performed in four (5%) patients.
Conclusion: The incidence of pathology was very low in children referred for tall stature, and few children were potential candidates for adult height reduction. We propose a simple diagnostic algorithm for clinical practice.

Objective: To investigate the relationship between low-grade inflammation (LI) and increased arterial stiffness in Chinese youth and adolescents with newly-diagnosed type 2 diabetes mellitus (T2DM).
Methods: Ninety-eight subjects aged 10 to 24 years with newly-diagnosed T2DM were investigated for findings of general inflammation. Anthropometric measurements were taken. Data related to arterial stiffness [brachial artery distensibility (Branch D), augmentation index (AIx), carotid-femoral pulse wave velocity (CF-PWV)] were collected. The subjects were divided into a non-LI group (NLI, n=42) and a LI group (n=56) according to their high-sensitivity C-reactive protein (Hs-CRP) levels.
Results: There were no significant differences in age and gender between the LI group and the NLI group. CF-PWV and AIx values of the LI group were higher than those of the NLI group (p<0.01), while Branch D values were lower in the LI group (p<0.01). Branch D, CF-PWV, and AIx values correlated significantly with Hs-CRP overall (r=-0.32, 0.34, 0.33, all p<0.01). Multivariate models revealed that in either group (LI or NLI), Hs-CRP, as a continuous variable, was an independent determinant of arterial stiffness parameters even after adjusting for other risk factors.
Conclusion: Newly-diagnosed T2DM youth and adolescents with LI present a more adverse cardiovascular disease risk profile and stiffer arteries. Hs-CRP levels correlated with arterial stiffness parameters and constituted an independent determinant of arterial stiffness.

Objective: There is some evidence indicating that histopathological changes in type 1 diabetes mellitus (T1DM) emerge before onset of microalbuminuria. The aim of our study was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) levels can be considered as an early sign of diabetic kidney injury.
Methods: Urine NGAL (uNGAL) levels and urinary NGAL/creatinine ratio (uNGAL/Cr) were assessed in 76 patients with T1DM and compared with the findings of 35 healthy individuals. The relationship of uNGAL levels with diabetes duration, body mass index (BMI), serum lipids, HbA1c, and microalbuminuria was also evaluated.
Results: Mean uNGAL (100.16±108.28 ng/mL) and uNGAL/Cr (118.93-117.97 ng/mg) levels in both microalbuminuric and non-microalbuminuric diabetic patients were found to be higher than those in the control group (uNGAL: 21.46±18.59 ng/mL and uNGAL/Cr: 32.1±51.48 ng/mg) (p=0.0001).
Conclusion: Urine NGAL level increases in the very early phase of T1DM before microalbuminuria develops. The patients with T1DM should be considered to have diabetic kidney injury from the time of diagnosis on and preventive interventions need to be initiated at an early stage to preclude the progression to end-stage renal disease.

Objective: This study aimed to integrate the existing updated reference standards for the growth of Turkish infants and children and to compare these values with World Health Organization (WHO) reference data, data from some European countries, and also with previous local data. Weight, height, and head circumference measurements were obtained on 2,391 boys and 2,102 girls who were regular attenders of a well child clinic and on 1,100 boys and 1,020 girls attending schools in relatively well-off districts in Ýstanbul. Mean number of measurements per child was 8.2±3.6 in the age group 0-5 years and 5.5±3.3 in the age group 6-18 years. All children were from well-to-do families and all were healthy. All measurements with the exception of measurements at birth, which were based on reported values, were done by trained personnel.
Methods: The LMS method was used in the analyses and in the construction of the percentile charts. There is an increase in weight for age and body mass index values for age starting in prepubertal ages, indicating an increasing trend for obesity.
Results: Compared to WHO reference data, weight and height values in Turkish children were slightly higher in infants and in children younger than 5 years, while they showed similarity to those reported for children from Norway and Belgium. Head circumference values, which were slightly higher than the WHO references in the first 5 years, were comparable to the data on Belgian and Norwegian children in the first 9 years of life. At older ages, Turkish children showed higher values for head circumference.
Conclusion: The relatively larger head circumference values were interpreted to reflect a genetic characteristic.

Objective: The aim of this study was to examine the vitamin D status of children and to determine the factors influencing serum 25-hydroxyvitamin D [25(OH)D] concentration in Turkish infants living in Ýzmir.
Methods: In this study, we examined the serum 25(OH)D levels of 100 infants aged 1 to 24 months and of 22 mothers from Ýzmir, Turkey. The study also included a questionnaire given to the mothers to acquire data on the demographic characteristics of the infants and their mothers as well as information on vitamin D supplementation, clothing habits, and sunlight exposure.
Results: Vitamin D deficiency was present in 31% of infants and 81.8% of mothers. Twenty-four male (42.9%) and 7 female (15.9%) infants were found to be vitamin D deficient (<20 mg/dL); 9 male (16.1%) and 17 female (38.6%) infants to be vitamin D insufficient (20-30 mg/dL); and 23 male (41.1%) and 20 female (45.5%) infants were vitamin D sufficient (>30 mg/dL). Only 63% of the infants were receiving vitamin D supplementation and 52% were said to be having regular exposure to sunlight. Mean serum vitamin D levels were lower in infants whose mothers were dressed according to the culture of traditional covered clothing (44%) compared to those infants whose mothers’ dressing style provided more exposure to sunlight.
Conclusion: We conclude that low exposure to sunlight, inadequate use of vitamin D supplementation, and large family size are factors influencing the vitamin D status of Turkish children living in the inner city of Ýzmir.

Objective: Idiopathic short stature (ISS) constitutes a heterogeneous group of short stature which is not associated with an endocrine or other identifiable cause. Some ISS patients may have varying degrees of insulin-like growth factor-1 (IGF-1) deficiency. Recombinant growth hormone (rGH) treatment has been used by some authors with variable results. Reports on long-term rGH treatment are limited.
Methods: In this study, 21 slowly growing, non-GH-deficient ISS children who received rGH treatment for 3.62±0.92 years were evaluated at the end of a 5.42±1.67-year follow-up period. The study group included patients with low IGF-1 levels who also responded well to an IGF generation test. The patients were divided into two groups as good responders [height increment >1 standard deviation (SD)] and poor responders (height increment <1 SD) at the end of the follow-up period.
Results: The height of the patients improved from -3.16±0.46 SD score (SDS) to -1.9±0.66 SDS. At the end of the follow-up period, mean height SDS was -1.72. Eleven of the patients showed a good response to treatment. Clinical parameters were essentially similar in the good responders and the poor responders groups. A female preponderance was noted in the good responders group.
Conclusion: rGH treatment can safely be used in ISS children. Long-term GH treatment will ameliorate the height deficit and almost 40% of patients may reach their target height.

Objective: The aims of this study were to demonstrate ventricular function changes in patients with congenital hypothyroidism and to investigate whether there is an association between any such changes and thyroid-stimulating hormone (TSH) levels using M-mode and Doppler electrocardiography (ECG) and tissue Doppler imaging (TDI).
Methods: Twenty-seven patients 5-30 days of age with congenital hypothyroidism who were scheduled to receive L-thyroxine treatment and 20 healthy newborns were included in this study. Twelve-lead ECG and M-mode TDI recordings of the patient and healthy groups were obtained. The patient group was divided into two subgroups according to TSH level (>100 uIU/mL or <100 uIU/mL), which were then compared on all parameters.
Results: Decreases were observed in the ejection fraction (EF), shortening fraction (SF), and mitral lateral annulus, mitral septal annulus, and tricuspid lateral annulus systolic velocity (Sa) on TDI, whereas left ventricular end-systolic diameter (LVESd) and corrected QT interval (QTc) dispersion were significantly increased in the patient group compared with the control group. No significant differences between the groups were found in left ventricular end-diastolic diameter (LVEDd) or heart rate. When the two patient subgroups (TSH >100 uIU/mL and <100 uIU/mL) were compared, TDI septal annulus Sa wave length and heart rate were significantly lower in the TSH >100 group.
Conclusion: Impairment in left ventricular systolic function and increased risk of arrhythmia were observed in newborn infants with congenital hypothyroidism. TSH level was associated with heart rate and interventricular septum velocity.

Objective: The study aimed to determine the level of knowledge and the sources of information about normal puberty and menstrual patterns in Turkish schoolgirls from Ýstanbul.
Methods: The study sample was comprised of 922 randomly chosen schoolgirls. A questionnaire survey of knowledge of normal pubertal development and menstrual patterns was conducted.
Results: The age of the girls ranged between 10 and 17 years and 82.3% had had menarche. The leading source of pubertal information was the mothers (84.2%). There was no statistically significant relationship between the mothers’ education level and the level of knowledge of the students about pubertal development (p>0.05). The main source for 18% of students was their teacher, but only 6% had a preference for their teacher providing education on this topic. Students who attained menarche preferred education about puberty to be given by health professionals and to both genders at the same setting (p<0.01). A total of 31.5% of students thought that the first symptom of puberty was acne. Half (50.7%) of the students did not know the time period between the beginning of puberty and menarche. The girls who had attained menarche were more knowledgeable about puberty, largely through their own experience.
Conclusion: This study shows that schoolgirls have an insufficient level of knowledge about normal puberty. Education programs must be conducted for students and their parents.

Objective: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, and mutations in the thyroid peroxidase (TPO) gene have been reported to cause the disease. Our aim in this study was to determine the genetic basis of CH in two affected children coming from a consanguineous family.
Methods: First, we investigated the potential genetic linkage of the family to any known CH locus using microsatellite markers and then screened for mutations in the linked gene by Sanger sequencing. By using next-generation sequencing, we also checked if any other mutation was present in the remaining 10 causative CH genes.
Results: The family showed potential linkage to the TPO gene, and we detected a homozygous nonsense mutation (R540X) in both cases. The two patients had total iodide organification defect (TIOD). Both the microsatellite marker haplotypes and the mutation segregated with the disease status in the family, i.e. all healthy subjects were either heterozygous carriers or homozygous wild-type, confirming the pathogenic nature of the mutation. Neither was the mutation present in any of the 400 control chromosomes nor were there any other mutations in the remaining causative CH genes.
Conclusion: This study proves the pathogenicity of R540X mutation and demonstrates the strong genotype/phenotype correlation associated with this mutation. It also highlights the power of working with familial cases in revealing the molecular basis of CH and in establishing accurate genotype/phenotype relationships associated with disease causing mutations.

Congenital adrenal hyperplasia (CAH) describes a group of disorders characterized by enzyme defects in adrenal steroidogenesis. 21-hydroxylase deficiency (21-OHD) is the most commonly encountered form. The analysis of steroids in pediatric cases requires high-sensitivity assays. A 14-year-old Syrian girl was referred for evaluation of short stature, amenorrhea, and hirsutism. On physical examination, breast development was Tanner stage 1. She had a phallic clitoris with a single urogenital orifice. Laboratory findings revealed primary adrenal deficiency with high androgen levels and low levels of 17-hydroxyprogesterone (17-OHP), (<0.05 ng/mL) and estrogen. This unexpected result led to suspicion of a high-dose hook effect. The measurement was repeated after 1/10 dilution of serum, and a high level of 17-OHP (115.4 ng/mL) was detected with the same test-enzyme-linked immunosorbent assay (ELISA). Simple virilizing form of CAH (21-OHD) was suspected and confirmed with genetic analysis. After initiation of glucocorticoid therapy, breast development was noted along with a decrease in testosterone level and an increase in estrogen level. To our knowledge, this is the first case report of hook effect for 17-OHP immunoassay in a patient with 21-OHD. High-dose hook effect should be suspected in patients with CAH when the test results are incompatible with one another. Additionally, this case demonstrates that a high testosterone level can block aromatase activity and consequently also estrogen production and breast development.

Primary hyperparathyroidism (PHPT) in children and adolescents is a rare condition. PHPT is usually sporadic and caused by parathyroid adenoma. Patients may present with bone pain, proximal myopathy, bony deformities, fractures, renal calculi, mass on the neck, or acute pancreatitis. A sixteen-year-old boy presented to our outpatient clinic with difficulty in walking due to swelling of both ankles. Ultrasonography revealed intratendinous calcific nodules in both Achilles tendons. Serum biochemistry showed hypercalcemia and hypophosphatemia. Serum parathormone level was high (512 pg/mL). Parathyroid scanning revealed a suspected parathyroid adenoma. The patient underwent parathyroidectomy and the diagnosis of parathyroid adenoma was confirmed by histopathology. Serum levels of parathyroid hormone, phosphate, and calcium returned to normal, and the tenderness over the Achilles tendon and the flow pattern on Doppler examination disappeared as well. In conclusion, hyperparathyroidism should be kept in mind in the differential diagnosis of tendonopathies. Early diagnosis can be crucial for prevention of severe complications.

Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X[97,3]/46,XY[2,7] and 45,X[92,7]/46,XY[4,5]/47,XYY [2,8] mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor.

Inflammatory myofibroblastic tumors (IMT) develop as a non-neoplastic proliferation of myofibroblasts in a myxoid to collagenous stroma admixed with inflammatory cells. The symptoms depend on the specific location of the tumor, which can be anywhere, but is particularly in the respiratory system. Thus, patients with IMT can present with a variety of findings. A pediatric patient with IMT who presented with cough, breathlessness, polyuria-polydipsia, and convulsions is described in this report.

Hypoparathyroidism, deafness, and renal dysplasia (HDR; OMIM 146255) syndrome is a rare disease, inherited dominantly and found to be related with GATA3 (GATA binding protein 3) gene mutations. A 13-year and 8-month-old boy who presented with hypocalcemia was diagnosed with hypoparathyroidism. He also had dysmorphic facial features, renal anomaly (pelvic kidney), and mild sensorineural hearing loss. His cranial computed tomography revealed multiple calcifications in bilateral centrum semiovale, corona radiata, and basal ganglions suggesting a persistent hypoparathyroidism. Thus, the presence of triad of HDR syndrome was considered, and genetic analysis using a next-generation sequencer identified a novel de novo missense mutation in exon 4 p.R276Q (c.827G>A) of GATA3 gene. This is the second patient who was reported to have a mutation in GATA3 gene from Turkey. In conclusion, although HDR syndrome is a rare condition, it should be kept in mind in patients with hypoparathyroidism. Classical triad can easily be identified if patients diagnosed with hypoparathyroidism are also evaluated with a urinary tract ultrasound and an audiometer.

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves’ disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation.