Genetic, hormonal, and anatomical factors are believed to be involved in the etiology of undescended testes. Due to increased risk of infertility, testicular cancer, torsion and/or accompanying inguinal hernia (>90%) as well as cosmetic concerns, all these patients require treatment. In this review paper, we aimed to evaluate the success rates of treatment modalities used in undescended testes, beginning from 1930 to the present, and to draw attention to the possible risks and benefits and also the efficacy of hormonal therapy in the management of the disorder, which is still a controversial issue. Hormonal therapy may lead to penile growth, painful erection, and behavioral changes while on treatment. In recent years, it has been reported that human chorionic gonadotropin (hCG) treatment was associated with interstitial edema due to increased vascular permeability, inflammation-like changes, and several adverse effects on germ cells by increasing pressure and apoptotic process. It has also been reported that LHRH analogues have positive effects on germ cells by increasing fertility in patients undergoing unilateral or bilateral orchiopexy. In some studies, the success rate of hCG treatment was reported to be higher following buserelin. In some other studies, hCG treatment was recommended before orchiopexy to reduce the risk for surgical ischemia. There are a limited number of randomized controlled studies, so evidence showing the efficacy of hormonal therapy is insufficient. According to the 2007 Consensus Report of Nordic countries, it is recommended that surgery is the first-line treatment modality in undescended testes and that it should be performed by pediatric surgeons and urologists at the age of 6-12 months.

Objective: To assess the Turkish National Newborn Screening Programme (NNSP) for congenital hypothyroidism (CH). Retrospective study based on the data from NNSP.
Methods: Since December 2006, a nationwide screening programme for CH has been conducted in Turkey by the Turkish Directorate of Public Health (TDPH) in cooperation with several institutions. We evaluated the database between January 2008 and July 2010 of this programme. According to the methodology of the NNSP, between three and five days of age (or at discharge from the hospital, if this occurs earlier) blood specimens were routinely collected from neonates on filter paper, by puncturing the heel. The accepted thyroid-stimulating hormone cut-off level for recall was 20 mU/L initially and 15 mU/L subsequently. The incidence of possible CH by years was reported.
Results: During the evaluation period, 3223765 newborns were tested. The mean annual incidence of possible CH showed a gradual increase over the years (1: 888 in 2008, 1: 592 in 2009, and 1: 469 in 2010). Regional differences were noted. Although the mean age of blood sampling did not change by years, the mean age at notification for suspected CH decreased from 19.2 to 15.7 days from 2008 to 2010.
Conclusions: We reported the first assessment of NNSP in Turkey. An improvement in performance measures for the CH screening programme has been noted. Knowledge on incidence of confirmed CH is not yet available in the database.

Objective: To investigate whether glycosylated hemoglobin (HbA1c) and 1-hour glucose level in oral glucose tolerance test (OGTT) are useful parameters for evaluation of glucose homeostasis in childhood.
Methods: The medical records of 106 obese/overweight children aged from 7 to 18 years who underwent OGTT were evaluated retrospectively. The subjects were divided into 2 groups according to their one-hour glucose concentration. Group 1 consisted of subjects whose one-hour glucose level was <155 mg/dL, and Group 2 consisted of subjects whose one-hour glucose level was ?155 mg/dL. The fasting and 2-hour glucose concentrations of the groups were compared. The sensitivity and specificity levels were determined using the ROC curve to assess the predictive value of HbA1c for impaired glucose tolerance (IGT).
Results: The mean 2-hour glucose concentration of the subjects in Group 2 was significantly higher than that of the subjects in Group 1 (137.8±35.5 mg/dL versus 113.1±21.2 mg/dL, p<0.05). If a 5.5% cut-off value for HbA1c was accepted as predictor of IGT, the sensitivity was 63% and specificity was 70%. 31% of the subjects with HbA1c levels at or above 5.5% had IGT. This rate was significantly lower in subjects who had HbA1c levels below 5.5% (p<0.05).
Conclusions: Obese/overweight children and adolescents whose 1-hour glucose level is ?155 mg/dL in the standard OGTT carry a high risk for IGT. Obese/overweight children and adolescents whose HbA1c level is at or above 5.5% may have IGT even though their fasting glucose level is normal, thus, OGTT is necessary to evaluate the glucose tolerance.

Objective: Morning cortisol levels are frequently used as screening tests for adrenal insufficiency in both adults and children. Reports differ on the specificity of this measurement. The present study was undertaken to determine whether sex or pubertal status affected morning cortisol values.
Methods: We measured morning cortisol levels and performed low-dose adrenocorticotropic hormone stimulation test in 35 healthy male and female subjects (ages 6-34) ranging in Tanner stage (TS) from TS 1 to TS 5. Testing was initiated at 08: 00 after an overnight fast. Morning serum total cortisol, free cortisol, cortisol-binding globulin, estradiol (males and females), and testosterone (males) were obtained.
Results: Morning total and free cortisol levels were significantly higher in TS 5 participants than in prepubertal children. Using a morning cortisol of 248 nmol/L to define a normal value, 19/21(90%) of healthy TS 5 subjects exhibit normal values. In contrast, 0/8 TS 1 healthy subjects exhibited a value greater than 248 nmol/L (p=0.0005). We also observed sex differences in morning cortisol levels in pubertal but not in prepubertal subjects. We observed sex differences in morning cortisol levels in TS 5 individuals.
Conclusions: Morning cortisol measurements may be more useful as screening tests for adrenal function in adults than in children. TS and sex may be considered in the decision to screen for adrenal insufficiency using morning cortisol or whether to proceed directly to stimulation testing.

Objective: Iodine deficiency and excess are the most important factors that affect screening and recall rates of congenital hypothyroidism. The purpose of this study was to investigate the urinary iodine status in newborns and their mothers and its effects on neonatal thyroid-stimulating hormone (TSH) levels in a mildly iodine-deficient area.
Methods: A total of 116 newborns and their mothers were included in the study. Urinary iodine levels were measured from healthy mothers and their babies on the 5th day following birth. Neonatal TSH levels were screened, and TSH and free thyroxine (fT4) levels were measured on the15th day in the recall cases. T4 treatment was started in infants with high TSH and low fT4 levels. These measurements were repeated on the 30th day in these newborns.
Results: Ninety-nine percent of the mothers included in the study were using iodized salt. The median urinary iodine level in the newborns was 279 µg/L, while it was 84 µg/L in their mothers. The rate of iodine deficiency among the mothers was 56.8%, and the rate of iodine excess was 8.6%. This rate was 10.3% for iodine deficiency and 61.2% for iodine excess in the newborns. The recall rate at the screening was 9.5% (n=11). The urinary iodine levels were above 200 µg/L in three newborns who had transient hyperthyrotropinemia.
Conclusions: Iodine deficiency was more frequently observed in nursing mothers, and iodine excess was more frequently seen in their newborns. The iodine excess noted in the newborns was attributed to the use of antiseptics containing iodine. The iodine excess leads to increases in recall rates, screening costs, and frequency of transient hyperthyrotropinemia.

Objective: The aim of the present study was to evaluate the outcome of radioiodine treatment in thyrotoxicosis in childhood and adolescence.
Methods: This was a retrospective study of 27 patients (ages 7.2- 19.8 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2007 to December 2011 in the Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Chiang Mai University. Gender, duration of antithyroid drug (ATD) treatment, 24-hour I-131 uptake, thyroid weight, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded.
Results: The outcomes of 27 patients (85.2% female, 14.8% male) treated with radioactive iodine were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents received 150 µCi of I-131/g of thyroid tissue (n=27). Six 6 months after treatment, 44.5% of the patients were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Of the 12 cases with hyperthyroidism, 2 cases needed a second dose of I-131 treatment, and they finally reached a hypothyroid state. The patients were classified into 2 groups according to treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences in age, gender, duration of ATD treatment, 2- and 24-hour I-131 uptake, thyroid weight, and total I-131 dose between these two groups.
Conclusions: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. It is suitable as a good second-line therapy for patients with severe complications, those who show poor compliance, and those who fail to respond to ATD treatment.

Objective: Variability in the incidence of type 1 diabetes mellitus (T1DM) related to geographical region, ethnic background, gender, and age indicates a need for further epidemiological studies. To date, there are no reported studies on the incidence of T1DM in the pediatric age group from the Southeastern region of Turkey. To define the incidence, demographic and clinical characteristics of T1DM in children 0-14 years of age in Diyarbakir, one of the largest cities in the Southeast region of Turkey.
Methods: Hospital files of patients with the diagnosis of T1DM were reviewed. Data of all patients diagnosed between 1 June 2010 and 31 May 2011 were evaluated. Population data on the 0-14 age group were obtained from the Turkish Statistical Institute (TSI) reports.
Results: From a total of 41 T1DM patients, 24 (58.5%) were female (male: 41.5%) with a male/female ratio of 1.4. The overall annual incidence of T1DM was 7.2/105, being 8.7/105 in females and 5.7/105 in males. The peak incidence was found to occur at age 5-9 years in the girls and 10-14 years in the boys. Mean age at diagnosis was 8.1±3.8 years. Rate of presentation with diabetic ketoacidosis was 65.9%. Patients applied most frequently in spring and winter months.
Conclusions: In this first T1DM incidence study on the pediatric age group in Diyarbakir, Turkey, T1DM incidence was found to be similar to that in countries with low-middle incidence.

Objective: To assess insulin-like growth factor-1 (IGF-1)/IGF-binding protein-3 (IGFBP-3) axis and insulin resistance (IR) and the relationship of these parameters with growth in appropriate for gestational age (AGA) and small for gestational age (SGA) infants at birth and in early infancy.
Methods: Postnatal blood samples for measurement of glucose, insulin, IGF-1, and IGFBP-3 were taken from 60 infants (30 AGA and 30 SGA) at birth and at one, three, and six months of age. Both SGA and AGA infants were divided into two groups: growing well and not growing well. Blood glucose, insulin, IGF-1, and IGFBP-3 values were assessed in all infants.
Results: Homeostasis model assessment-IR (HOMA-IR) values in well-growing SGA infants in the third and sixth months were found to be higher than in not well-growing SGA infants (3.9±0.8 vs. 1.0±0.3 at 3 months and 3.3±0.9 vs. 2.4±0.9 at 6 months, p<0.05). IGF-1 levels in well-growing SGA infants at 3 and 6 months were found to be higher than those in not well-growing SGA infants (83.80±44.50 vs. 73.50±17.60 ng/mL at 3 months and 95.12±50.74 vs. 87.67±22.91 ng/mL at 6 months, p<0.05). The IGF-1 values were significantly lower in well-growing SGA infants than in well-growing AGA infants (83.80±44.50 vs. 103.31±30.81 ng/mL at 3 months and 95.12±50.74 vs. 110.87±26.44 ng/mL at 6 months, p<0.05).
Conclusions: This study demonstrates the effects of accelerated early infant growth on IGF-1/IGFBP-3 axis in SGA-born infants.

Objective: To assess the effect of education and economic status of parents on obesity in children.
Methods: A cross-sectional survey was conducted in 2006 among school children in Riyadh, Saudi Arabia. A representative sample of 1243 (542 male and 701 female) children aged 6-16 years were contacted using multistage cluster sampling strategy. Social and demographic variables were collected using questionnaires completed by parents. Height and weight of the children were recorded by a trained team.
Results: The mean body mass index for all children was 19.8±5.4. The prevalence rates of overweight and obesity were 21.1% and 12.7%, respectively. Overweight and obesity were more prevalent in males than in females. By multivariate analysis, children were more likely to be overweight if they were male (OR=0.6, p<0.01), 12 years of age (OR=3.79, p<0.01, compared to age 6 years), and if their families had higher income (OR=3.12, p<0.01, compared to families with low income). Being male (OR=0.545, p <0.01), aged 12 years (OR=3.9, p=0.005, compared to the age of 6), and having a mother who is more educated were determined to be significant risk factors for obesity in children. Mothers educated at university level were found to have a three-fold higher risk of having obese children (OR=3.4, p<0.01, compared to mothers with lower education levels).
Conclusions: Overweight and obesity among Saudi children is associated with educated mothers and higher family income. This finding calls for introducing interventions in health education for both children and parents.

Objective: Although the association between Down’s syndrome (DS) and thyroid dysfunction is well recognized, the cause of this condition is not known.
Methods: Hospital records of patients with DS and hypothyroidism referred to our clinic were retrospectively reviewed. Initial thyroid hormone and thyrotropin (TSH) levels, age at admission, initial anthropometric measurements, age at the beginning of therapy, initial L-thyroxine (L-T4) doses, time to normalization of the thyroid function tests, and L-T4 dose at last visit were recorded. Thyroid ultrasound imaging was used to measure the size of the gland. Descriptive data were expressed as mean±SD values. Skewed data were shown as median and interquartile ranges (IQR).
Results: There were 62 patients with DS (32 male and 30 female). Median TSH level at the first visit was 10.40 (19.4) µIU/mL and median free T4 level was 1.18 (0.43) ng/dL. There was no statistical difference in terms of age, hormone and antibody levels, thyroid volume and L-T4 doses between boys and girls. Thyroid volumes of 54 patients were measured. Only nine of these patients had a normal-sized thyroid gland. Median total thyroid volume was 0.89 (2.07) mL. Thyroid volume was negatively correlated to L-T4 dose at last visit (p=0.006, r=-0.387).
Conclusions: We found a high prevalence of thyroid dysgenesis in patients with DS and hypothyroidism. This association has not been reported before. Further studies investigating the thyroid gland size in these patients need to be performed to confirm the results.

Lipoid congenital adrenal hyperplasia (LCAH), a rare disorder of steroid biosynthesis, is the most severe form of CAH. We report novel molecular findings of three unrelated infants with LCAH diagnosed at our center. A known missense mutation c.653C>T (p.A218V) and two novel mutations [premature termination c.441G>A (or p.W147X) and frameshift deletion c.del815G (or p.R272PfsX35)] were identified after complete sequencing of the STAR gene. Prenatal diagnosis was carried out for the family with mutation c.815delG by molecular testing wherein the fetus was found to be homozygous for the mutation. This is the first report of molecular diagnosis and prenatal testing for LCAH from India.

Neonatal diabetes mellitus (NDM) is a rare form of diabetes that presents within the first six months of life. Nearly 70% of these cases have loss of methylation at the differentially methylated region on chromosome 6q24. To describe the findings in a Turkish male patient with NDM caused by a loss of methylation at chromosome 6q24 and three novel homozygous mutations in the ZFP57 gene, methylation-specific PCR was carried out at 6q24 and mutation analysis of ZFP57 gene was maintained by direct sequencing. Sequencing of ZFP57 gene revealed the hypomethylation of chromosome 6q24 and three novel mutations (chr6:29.641.413 A>T, 29.641.073 C>T, and 29.640.855 G>C), respectively. The latter mutation seems to display the patient’s condition due to a highly conservative amino acid substitution in the protein. We suggest the ZFP57 gene as a causative factor for NDM and it should be considered in genetic testing. Further studies including functional analysis of the detected mutations will provide precise information regarding the effect of the mutations.

Aromatase deficiency (AD) is a rare autosomal recessive inheritance syndrome. Its worldwide incidence is unknown, and there are few case reports in the literature. Aromatase dysfunction develops due to CYP19A1 gene mutation and a decrease in estrogen synthesis. Estrogen deficiency can induce delayed epiphyseal closure, eunuchoid body habitus, osteopenia, and osteoporosis in both genders. Our patient was a 27-year-old male who presented with bone pain, recurrent bone fractures associated with minimal trauma starting in puberty, and a progressive increase in height. Laboratory tests revealed that the blood levels of follicle-stimulating hormone and luteinizing hormone were above normal, testosterone level was normal, and estrogen was undetectable. Plain bone radiography of the left wrist and hand demonstrated that the epiphyses were still unfused. Lumbar osteoporosis was detected in bone densitometry. In the genetic analysis, homozygous R375H guanine-adenine (G-A) mutation was detected in the CYP19A1 gene, and a diagnosis of AD was reached. Treatment with 25 µg transdermal estradiol was started. All family members were examined. Homozygous R375H G-A mutation was detected in the patient’s younger brother. Heterozygous R375H G-A mutation was found in his mother, father, and older brother. In conclusion, this AD patient requires lifetime estrogen replacement in order to provide sufficient bone mineralization, to reduce the risk of bone fractures, and to lead a healthy life. The best method to prevent the possible complications is to diagnose the AD syndrome at early ages and to provide adequate estrogen replacement starting at puberty.

Pseudonormoglycemic diabetic ketoacidosis (DKA) is a rare condition and has been reported only in a few adult patients. We present a 15-year-old girl with a 9-year history of type 1 diabetes who presented with euglycemic and extreme hypertriglyceridemia. The acidosis and hypertriglyceridemia resolved with intravenous insulin therapy and rehydration. Hyperlipidemia was the apparent cause of pseudonormoglycemia in this patient. The findings in the present case demonstrate that also in children, DKA can rarely occur without abnormal blood glucose levels. Assessment of the acid-base status, urinary glucose, and ketone readings is therefore important in all diabetic patients who are unwell at admission and have normal glucose levels. In such patients, hyperlipidemia may cause pseudonormoglycemia. An awareness of this rare treatable life-threatening condition is important.

Vitamin D intoxication usually occurs as a result of inappropriate use of vitamin D preparations and can lead to life-threatening hypercalcemia. It is also known that there are a number of physicians who prescribe vitamin D supplements for various clinical conditions, such as poor appetite and failure to thrive. While inappropriate use of vitamin D supplements may lead to vitamin D intoxication, there are no reports of cases of vitamin D toxicity due to manufacturing errors of vitamin D preparations. Here, we present cases of hypervitaminosis D which developed following the use of a standard dose of a multivitamin preparation. All three cases presented with hypercalcemia symptoms and had characteristic laboratory findings such as hypercalcemia, hypercalciuria, low levels of parathyroid hormone. The very high serum 25(OH) vitamin D levels in these patients indicated vitamin D excess. The vitamin D level of the prescribed multivitamin preparation in the market was studied and was found to contain a very low level of vitamin D (10 IU/5 mL). Although the stated vitamin D content of the preparations ingested by these patients was not high, unproven but possible manufacturing errors were considered to be a possible cause of the hypervitaminosis D diagnosed in these three patients.