Volume 25, Issue 7-8

No abstract available.

Congenital hyperinsulinism (CHI) during infancy is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia. This can lead to irreversible severe neurological damage in the infant. There are two main histologic subtypes: diffuse and focal, both of which may require different surgical strategies. It is very important to differentiate focal leisons from diffuse leisons. However, the differentiation of diffuse leisons from focal leisons is challenging. Affected pancreatic areas utilize dihydroxyphenylalanine (DOPA) at a higher rate than normal pancreatic tissues; thus, labeling of L-DOPA with fluorine-18 (18F-DOPA) allows functional mapping of hyperinsulinism using positron emission tomography/computed tomography (PET/CT). In this article, we reviewed the 18F-DOPA PET/CT application in CHI. The aim of this review is to enhance the recognition of 18F-DOPA PET/CT application in the diagnosis of CHI.

Propylthiouracil (PTU), carbimazole (CMZ) and methimazole (MMI) are the most common drugs used today in cases of adolescent thyrotoxicosis. Skepticism has been growing regarding the use of PTU in childhood and its association with severe liver failure. The aim of this review is to present all the recent data regarding pathogenesis of PTU hepatotoxicity in children and adolescents. Specifically, reactive drug metabolites and increased oxidative stress can directly activate inflammatory and immunological pathways. Drugs are not only immunogenic because of their chemical reactivity but also because they may bind through electrostatic forces to available T-cell receptors. Redox modulation is also a key regulatory strategy in the adaptive immune system. Subtle changes in the extracellular redox status may cause profound functional changes in redox-sensitive proteins. Genetic factors that affect drug biotransformation could also be implicated in this mechanistic model of PTU-related hepatotoxicity. Further studies are needed to fully understand the pathophysiology of PTU-induced liver damage.

No abstract available.

Objective: The aims of this study were to analyze the role of fine-needle aspiration biopsy (FNAB) in the management of pediatric thyroid nodules and to analyze the malignancy risk of thyroid nodules by studying the association between autoimmune thyroiditis and thyroid cancer. Methods: We conducted a retrospective study on 111 patients with thyroid nodules diagnosed in childhood or adolescence. FNAB was performed in 46 participants with thyroid nodules after ultrasonography (US). Cytology diagnoses were categorized as insufficient, benign, suspicious, and malignant. Clinical and surgical follow-up data were obtained from medical records. The clinical correlation and accuracy of FNABs were evaluated. Results: The family history was positive in four patients. Forty-six patients had positive antithyroid antibodies and an inhomogeneous hypoechogenic US pattern. One patient had previous neck irradiation history. Eighty-six patients (%77.5) were euthyroid. All patients underwent US examination. The FNAB results of the 46 patients were 29 (63%) benign cases, 7 (15%) insufficient, and 10 (22%) suspicious patients. Malignancy was not reported at all. A repetition of FNAB in two benign cases, which were diagnosed with papillary carcinoma during follow-up, reported these cases as suspicious. Ten patients with suspicious FNAB results underwent surgery because of increases in the size of the nodules; two patients were diagnosed with papillary carcinoma. In this study, the prevalence of malignancy was 4.5% in patients with thyroid nodules. Conclusion: In this study, the importance of FNAB in the diagnosis and follow-up of thyroid nodules in childhood has been observed, and risk factors, such as history of familial thyroid carcinoma, radiotherapy to the neck at younger ages, suspicious cytological findings, and increased nodular sizes during follow-up in cases with Hashimoto thyroiditis have been correlated with increased thyroid carcinoma malignancy risk.

Aim: The aim of the study was to evaluate the role of selenium (Se) in childhood autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibody (TgAb), and thyroid morphology. Methods: Newly diagnosed 23 euthyroid children (mean age, 12.3±2.4 years) with Hashimoto thyroiditis (HT) received only 50 μg L-selenomethionine per day for 3 months. The baseline basal urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb changes at the 3rd month and then compared the thyroid morphology with 30 healthy individuals (mean age, 12.1±2.1 years) at the 6th month. Results: Serum TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A prominent decrease in thyroid volume was noteworthy; 35% of patients showed a thyroid volume regression rate of ≥30%. Conclusion: In terms of TPOAb and TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation seems to lead a favorable response in thyroid volume regression.

Background: A typical growth pattern with decreased pubertal growth spurt has been identified in patients with classical congenital adrenal hyperplasia (CAH). Objective: To evaluate the accuracy of final height predictions in patients with CAH using the Bayley and Pinneau (B&P) method. Patients and Methods: Using growth and final height data of 92 patients (57 F/35 M) with CAH due to 21-hydroxylase deficiency (38 SV/54 SW), final height predictions with the B&P method were compared to actual final heights. Results: In females, mean final height was 159.9±5.3 cm (–1.0±0.7 SDS) compared to predicted mean final height of 167.9±10.7 cm (+0.5±1.7 SDS), p<0.001, overestimation 7.3±9.5 cm. In males, mean final height was 170.1±6 cm (–1.2±0.8 SDS) compared to predicted mean final height of 185.6±13.4 cm (+1.2±1.9 SDS), p<0.001, overestimation 13.9±10.8 cm. Conclusion: In classical CAH, final height prediction using the B&P method results in significant overestimation of final height.

Aim: The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. Methods: A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Results: Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p<0.001; GHD, p=0.03) and their NFH (ISS, p<0.05; GHD, p=0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9±4.9 cm with combined therapy vs. 7.3±6.0 cm with GH; GHD children, an increase of 6.8±7.8 cm with combined therapy vs. 5±5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Conclusions: Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

Background: Human mutations in the gonadotropin-releasing hormone receptor (GnRHR) gene cause normosmic idiopathic hypogonadotropic hypogonadism (IHH). At least 19 different mutations have been identified in this G-protein-coupled receptor, which consist mostly of missense mutations. Objectives: To identify and determine the frequency of mutations in the coding region of the gonadotropin-releasing hormone receptor (GnRHR) gene in forty Chinese patients with normosmic idiopathic hypogonadotropic hypogonadism (IHH) and establish genotype/phenotype correlations where possible. Methods: The diagnosis of HH was based on absent or incomplete sexual development after 17 years of age in girls and 18 years in boys associated with low or normal levels of LH in both sexes and low levels of testosterone in males and of estradiol in females. All patients presented with a normal sense of smell in an olfactory specific test. Forty IHH patients and 40 controls were screened for mutations in the coding sequence of the GnRHR gene. The coding region of the GnRHR gene was amplified by PCR and directly sequenced. Results: A missense mutation, serine 168 arginine (S168R), located in the fourth transmembrane domain of the GnRHR gene, was identified as being in a homozygous state in one male with complete HH. The S168R mutation has been previously shown to be a cause in the complete loss of receptor function because hormone binding to the receptor is completely impaired. In another patient, a compound heterozygous mutation (Gln106Arg and Arg262Gln) was identified in a male with partial HH. The Gln106Arg mutation is located in the first extracellular loop of GnRH-R, this mutation decreases but not does eliminate GnRH binding; while Arg262Gln mutation is located in the third extracellular loop of GnRH-R and only decreases signal transduction. A good correlation between genotype and phenotype was found in our patients. The patient, who was homozygous for the completely inactivating S168R mutation, had complete HH. In addition, the affected patient who was compound heterozygous for the Gln106Arg – Arg262Gln mutations – has partial HH. Conclusions: GnRHR mutations can be classified into partial or complete loss of function mutations. Partially inactivating substitutions of the GnRHR frequently found in familial hypogonadotrophic hypogonadism are Q106R and R262Q. Comparison of compound heterozygous with homozygous patients suggests that their phenotype and the response to GnRH is determined by the GnRHR variant with the less severe loss of function.

Background: Turner syndrome (TS) patients usually have low bone mineral density (BMD) and increased risk of osteoporotic fractures. We have previously demonstrated an association of bb ( Bsm I polymorphic site) and ff ( Fok I polymorphic site) vitamin D receptor (VDR) genotypes with reduced BMD in TS patients. Aim: To analyze the relationship between VDR- Cdx 2 polymorphism and BMD as well as bone metabolic variables in TS patients. Methods: Fifty-five TS patients and 59 control women were studied. VDR- Cdx 2 genotypes were determined using TaqMan probes in a real time thermocycler. Lumbar and femoral BMD were determined by dual-energy X-ray absorptiometry (DEXA) and serum intact parathyroid hormone, osteocalcin and β-CrossLaps were determined by electrochemiluminescence. Results: Patients with genotype GG had higher levels of both osteocalcin and β-CrossLaps as compared to patients with genotype GA (p<0.01 and p<0.05, respectively). Conclusion: Patients carrying genotype GG have higher levels of bone formation and resorption markers. This indicates a more active bone turnover that could impact on their future bone mineral density.

Background: There is no consensus on the association between vitamin D and asthma. Objective: To determine the relationship between 25-hydroxyvitamin D [25(OH)D] levels and asthma symptom severity in children and adolescents. Methods: A retrospective, case-control study of 263 subjects of ages 2–19 years with asthma who were compared to 284 non-asthmatic controls of similar ages. Subjects were excluded if they had diseases of calcium or vitamin D metabolism or were receiving calcium or vitamin D supplementation. Serum 25(OH)D was measured in all subjects. Asthma symptom severity, usually stratified into 6 steps, was stratified into five steps [1–5] based on the number and dose of controller medications used as outlined by the National Heart, Lung, and Blood Institute’s guidelines. Mean 25(OH)D values were compared between the asthmatic patients and controls, as well as among the five steps of asthma symptom severity. Results were adjusted for age, sex, BMI, race and severity of asthma symptoms. Results: There was no difference in 25(OH)D between asthmatic patients and controls (28.64±10.09 vs. 28.42±11.47, p=1.0). However, there was a significant difference in 25(OH)D between obese and non-obese asthmatic patients (23.33±7.67 vs. 30.16±10.20, p<0.0001), as well as obese and non-obese controls (24.56±9.90 vs. 29.50±11.66, p=0.003). Mean 25(OH)D levels did not vary significantly among the five steps of asthma symptom severity. Conclusions: There were no differences in mean 25(OH)D levels between asthmatic patients and controls. Mean 25(OH)D level was significantly lower in both the obese asthmatic patients and obese controls. Asthma severity had no relationship to mean 25(OH)D levels.

Abstract: There are few reports of an association between Turner syndrome (TS) and 21-hydroxylase deficiency. However, this association is more frequent in some populations. The aim of this study was to evaluate the incidence of 21-hydroxylase deficiency in patients with TS in our population. 21-hydroxylase deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis, Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP), dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated. Patients with increased 17OHP responses in the stimulation test also underwent 21-hydroxylase gene analysis. The mean age was 14.6±4 (2.6–22.4); 37 patients were on growth hormone (GH) treatment. Nine patients were at prepubertal stage, whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP, and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic analysis. In other cases, peak 17OHP levels were ≤6 ng/mL. The mean peak 17OHP was 2.62±1.48 (1.19–7.5) ng/mL, the cortisol level was 37.6±8.43 (23.9–56.2) μg/dL and the DHEAS was 135.2±87.3 (15–413) μg/dL. The increased mean basal and peak cortisol levels (20.5±10.2 and 37.6±8.4 μg/dL) were remarkable findings. Whereas basal cortisol was above 20 μg/dL in 38.7% of patients, exaggerated results up to 56.2 μg/dL were obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were not correlated with the presence of puberty, chromosome structure, gonadal steroid use, obesity or growth hormone use. This trial suggested that 21-hydroxylase deficiency was not common among patients with TS in our population. Adrenal function should be assessed, at least in the presence of clitoral enlargement in patients with TS, particularly if their karyotype does not contain a Y chromosome.

Background: The fibroblast growth factor 23 (FGF23) is the most important hormonal regulator of circulating phosphate levels. Apart from this essential role, it may also act as a ‘hormone-like’ factor involved in glucose and lipid metabolism. It is believed to have a potential role in the development of insulin resistance. Aim: The aim of the study was to compare FGF23 levels between two groups of obese adolescents: insulin resistant and non-insulin resistant. Patients: The study included 36 obese, insulin-resistant adolescents (21 boys and 15 girls) of pubertal age (mean age, 13.95 years; Tanner stage IV or V). The control group consisted of 21 obese peers with normal HOMA-IR values. Methods: FGF23 levels were measured in a fasting blood sample by Human Intact FGF-23 ELISA Kit (Immunotopics Inc., San Clemente, CA, USA). A standard oral glucose tolerance test was performed, which assessed fasting and 120 min postload plasma glucose and serum insulin levels; the insulin resistance index HOMA-IR was calculated. The definition of insulin resistance was based on a HOMA-IR threshold set for adolescents (≥3.16). Results: There was a significant inverse correlation between FGF23 levels and HOMA-IR (R=–0.26, p<0.05) in the study group. FGF23 levels were also significantly lower in the study group (9.8 vs. 11.9 pg/mL, p=0.026). Conclusions: In adolescents with simple obesity and insulin resistance, FGF23 levels are lower compared with obese adolescents with normal HOMA-IR.

Objective: Recent reports suggest that ghrelin regulation may differ by ethnicity and age. This study was designed to examine circulating ghrelin among overweight female African Americans across different age groups. Methods: Eleven overweight peripubertal girls, 17 overweight pubertal girls, and a control group of 18 overweight African-American premenopausal women ingested a standard liquid meal after an overnight fast. Blood samples were obtained before the meal and for 4 h postchallenge. Participants rated appetite by a visual analog scale. Results: Peripubertal girls demonstrated higher postprandial ghrelin and lesser ghrelin suppression compared with adults (p<0.05), corresponding with greater desire to eat across the test period (p=0.017). Fasting ghrelin tended to be inversely related to fasting estradiol (r=–0.264, p=0.076). Conclusion: Compared with overweight African-American women, peripubertal girls had higher ghrelin as well as greater appetite after a standard meal. These results may suggest a dysregulation in ghrelin reflective of demands of growth.

Background: The effects of carbohydrate-restricted (ketogenic) diets on metabolic parameters in children have been incompletely assessed. Objective: To compare the efficacy and metabolic impact of ketogenic and hypocaloric diets in obese children and adolescents. Subjects: Fifty-eight obese subjects were placed on one of the two diets for 6 months. Methods: Anthropometric measurements, body composition, oral glucose/insulin tolerance test, lipidemic profile, high molecular weight (HMW) adiponectin, whole-body insulin sensitivity index (WBISI), and homeostatic model assessment-insulin resistance (HOMA-IR) were determined before and after each diet. Results: Both groups significantly reduced their weight, fat mass, waist circumference, fasting insulin, and HOMA-IR (p=0.009 for ketogenic and p=0.014 for hypocaloric), but the differences were greater in the ketogenic group. Both groups increased WBISI significantly, but only the ketogenic group increased HMW adiponectin significantly (p=0.025). Conclusions: The ketogenic diet revealed more pronounced improvements in weight loss and metabolic parameters than the hypocaloric diet and may be a feasible and safe alternative for children’s weight loss.

Objective: To construct waist percentiles for 6–11-year-old Turkish children in Elazig Province, Eastern Anatolia. Methods: This cross-sectional study was performed with 3342 (1708 boys and 1634 girls) children from March to June 2007. Waist circumferences (WC) were measured between the lowest rib and the superior iliac crest, and centile curves were constructed with the Lambda-Mu-Sigma (LMS) method. Results: Towards 6–11 years, WC 50th percentile ranged from 57.54 to 67.04 cm in boys and 55.77 to 64.58 cm in girls. For both genders, WC increased with age. At each age, boys had higher WC values than girls. For the entire sample, mean WC was 62.5±6.8 cm for boys and 59.8±6.2 cm for girls. Median WC was 62.0 cm (32.0–90.0) for boys and 59.0 cm (46.0–87.0) for girls. Conclusions: The large differences in the values obtained worldwide emphasize the necessity of providing population-specific WC reference curves from different populations, which in turn may result in an international reference standard similar to that provided for body mass index.

Objective: To investigate the relationship between soluble intercellular adhesion molecule (sICAM-1), vascular endothelial cell adhesion molecule (VCAM-1), monocytes chemotactic protein (MCP-1), von Willebrand factor (vWF), and coronary artery stenoses degree in coronary heart disease (CHD) within type 2 diabetes mellitus (T2DM) patients. Methods: A total of 92 subjects were treated with coronary angiography (CAG), including 62 subjects with CHD. The individuals were divided into three groups, group A (32 patients with CHD and T2DM), group B (30 patients with CHD but no T2DM) and group C (30 patients with no CHD and T2DM). All patients were treated with a Gensini coronary angiography check. The correlations between sICAM-1, VCAM-1, MCP-1 and vWF in peripheral blood and coronary artery stenosis degree were analyzed. Results: The average score of coronary artery stenosis degree was 30.75±12.67 in group A, which was significantly higher than group B (11.20±7.51) and group C (2.40±1.23) (p<0.01). The mean levels of sICAM-1, VCAM-1, MCP-1 and vWF in serum showed that group A was significantly higher than group B and group C (p<0.01), and also that group B was higher than group C. There were significant positive correlations between the degree of coronary artery stenosis and the mean level of sICAM-1, VCAM-1, MCP-1, vWF in group A (p<0.01), but these were not shown in group B and group C (p>0.05). Conclusions: Association analysis shown that the level of sICAM-1, VCAM-1, MCP-1 and vWF elevated in CHD with T2DM patients. Vascular endothelial dysfunction could be caused to the coronary artery stenosis pathophysiological process. Results from this study suggested that sICAM-1, VCAM-1, MCP-1 and vWF may contribute to the occurrence and development of vascular lesions in T2DM. These endothelial function related factors could be acceptable as a prediction and testing index of vascular complications in T2DM.

Persons with type 1 diabetes are at increased risk of developing vascular disease. Adiponectin concentrations may play an intermediate role in this process. We sought to determine whether adiponectin is correlated with vascular stiffness in adolescents with type 1 diabetes. Plasma adiponectin, pulse wave velocity (PWV), augmentation index (AIx-75), and brachial distensibility (BrachD) were collected in 225 adolescents. Outcomes were evaluated by sex, and regression models were used to determine whether adiponectin was an independent determinant of arterial stiffness. Males had lower adiponectin levels and stiffer vessels (lower BrachD, p<0.01) than females. Unadjusted correlations revealed that adiponectin was correlated with BrachD (p<0.01) but not PWV and AIx-75. After adjustment, adiponectin was not a significant predictor of BrachD. The most consistent predictors of increased stiffness were age, male sex, blood pressure, obesity, and total cholesterol (p<0.05). Adiponectin’s contributions to arterial stiffness appear to be masked by other cardiovascular risk factors in persons with type 1 diabetes.

The aim of this study was to assess the association between pancreatic and thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural growth. Seventy-two children with type 1 diabetes mellitus (T1DM) and no clinical evidence of thyroid disorders were evaluated: glycated haemoglobin (A1c), thyroid peroxidase antibodies (TPOAb), glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase antibodies (IA2A), and thyroid-stimulating hormone (TSH). The score of standard deviation for height (SDS) was calculated. There were 72 patients, 38 (52.7%) boys and 34 (47.2%) girls, with a mean age of 10.89±4.26 years and a mean duration of T1DM of 3.41±2.56 years. TPOAb were present in 23.6% of patients; 12.5% of subjects were positive for GADA and 41.6% for IA2A. Patients with TA had more prevalent GADA and IA2A (23.5% vs. 9%, p<0.001, and 58.8% vs. 36.3%, p<0.001, respectively). A1c was higher in patients with TA (9.7%±2.05% vs. 8.6%±2.11%, p=0.05). TA was associated with lower SDS (0.26 vs. 0.98, p=0.043). TSH was higher in patients with TA (3.39 vs. 2.15 μU/mL, p<0.05). Logistic regression analysis revealed that a negative SDS for height was independently associated with duration of diabetes (p=0.049) and TSH (p=0.027) but not with birth weight, A1c, and TPOAb. In conclusion, TA was found in 23.6% T1DM children. Patients with TA had significantly higher prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA. Our data suggest significant association between TA and height in children with T1DM. SDS was independently associated with diabetes duration and TSH.

Objective: To explore the relationship between nesfatin-1 and growth and development in newborns. Methods: Blood samples for nesfatin-1, ghrelin, insulin-like growth factor-1 (IGF-1), insulin and glucose were obtained from preterm (n=53) and term infants (n=60), including appropriate for gestational age (AGA) (n=32) and small for gestational age (SGA) infants (n=28). The relationship between nesfatin-1 and other metabolic hormones or anthropometric parameters was evaluated. Results: The concentrations of nesfatin-1, ghrelin and insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) were higher in SGA than AGA infants (p=0.0358, 0.0163, 0.0001 and 0.0051, respectively), but IGF-1 levels and homeostasis model assessment-insulin sensitivity index (HOMA-ISI) were lower (p=0.033 and 0.0001, respectively). Nesfatin-1 levels in SGA infants were higher on postnatal day 0 (PND0) than in AGA infants (p=0.0358) and lower on PND7 (p=0.0002) and PND28 (p=0.0488). A negative correlation showed between nesfatin-1 and oral calorie intake (r=–0.446; p=0.017) and HOMA-ISI (r=–0.398; p=0.036), and a positive correlation between nesfatin-1 and HOMA-IR (r=0.43; p=0.023) in SGA infants. Conclusion: Nesfatin-1 is involved in the physiological regulation of intrauterine and postnatal growth and development in SGA infants.

The objective was to determine the probability of receiving steroid treatment following an insulin tolerance test (ITT) for short-stature evaluation and to evaluate the utility of a subsequent cortrosyn stimulation test (CST) in determining adrenal sufficiency. We retrospectively analyzed the hypothalamic-pituitary-adrenal (HPA) axis evaluation in short-stature subjects during the 5-year period from January 2005 to December 2009. The probability of receiving steroid treatment was <10% when the maximum cortisol concentration during an ITT was <8.4 μg/dL. In the event of a suboptimal cortisol response during an ITT, only a single 1-μg CST is recommended for assessment of adrenal function.

Objective: To investigate the GCM2 gene in three siblings with congenital hypoparathyroidism and perform functional analysis. Materials and methods: We sequenced the GCM2 gene by PCR and analyzed the functional consequence of the mutation by transient transfection studies. Haplotype analysis was performed. Results: We identified a nucleotide change, c.408C>A, in exon 3 that is predicted to truncate the Gcm2 protein (p.Tyr136Ter). All three affected siblings were homozygous and both parents were heterozygous for the mutation. Transfection studies revealed the mutant mRNA but not expression of the Gcm2 protein. Haplotype analysis revealed that the two mutant GCM2 alleles shared genotypes on chromosome 6p24.2. Conclusions: We describe the first GCM2 mutation in exon 3 in patients with severe congenital hypoparathyroidism. Informative genetic markers could not exclude identity by descent for the mutant alleles. Gcm2 protein was not detected after transfection, suggesting that complete lack of Gcm2 action accounts for severe hypoparathyroidism.

Background: Ghrelin is an important mediator of energy balance and metabolism. The aim of this study was to investigate the relationship among ghrelin concentration, growth patterns, and immunological parameters in children with an impairment or inefficiency in functioning of the immune system. Methods: Twenty patients with primary immunodeficiency diseases (PIDs), 20 patients with recurrent respiratory tract infections (RRTIs), and 20 healthy children (control group) were included. The anthropometric measurements, ghrelin plasma levels, and selected immunological parameters were measured. Results: Ghrelin levels and nutritional status parameters (weight, height, and body mass index) values were negatively correlated only in the control group. Ghrelin negatively correlates with complement hemolytic activity in the PID group and with IgA serum level in the RRTI group. Conclusion: Our results show evidence that there is a relationship between ghrelin and nutritional status of healthy children but not in children with PID or RRTI.

Pubertal gynecomastia is the glandular proliferation of male breast tissue. It is regarded as a physiological phenomenon, arising due to a presumed transient imbalance in the ratio of free androgen to free estrogen. Treatment with tamoxifen, a selective estrogen receptor blocker, has been shown to effectively reduce the disc size and is generally considered for treatment when the disc diameter is >3–4 cm. For severe or persistent cases, surgery is considered the mainstay of treatment. We present three cases who reported dissatisfaction with the results of tamoxifen treatment and were therefore submitted to adenectomy by Webster’s technique preceded by liposuction. Pathology results showed adipose tissue alone, with no evidence of intraductal epithelial proliferation. The results showing a lack of residual glandular breast tissue after treatment using tamoxifen proves that it is effective in histopathologically eliminating pubertal gynecomastia.

Background : Over the last 10 years, several children, fetuses and women have been reported to be virilized through interpersonal transfer of testosterone (T) gel used by fathers or partners. Long-term exposure to androgens in children, such as in poorly controlled congenital adrenal hyperplasia, is known to promote central precocious puberty. Methods : Clinical case report. Results : We report on a 5-year-old boy who developed central precocious puberty after long-term (starting prenatally) exposure to testosterone through interpersonal transfer of T gel used by his father. We also report on another case illustrating that the recommended precautions are not sufficient to avoid interpersonal transfer of T gel among household contacts. Plasma testosterone levels and history-taking revealed the cause of virilisation and the testosterone contamination source in both cases. Given the increased testicular volume and persisting testosterone elevation after cessation of gel use in the first patient, a GnRH test was carried out and confirmed central precocious puberty. Conclusion : This is the first report of a boy with central precocious puberty occurring after long-term (starting prenatally) exposure to testosterone through the interpersonal transfer of T gel. This report questions whether central precocious puberty constitutes a long-term side effect of testosterone exposure in childhood through T gel use by a household contact.

The association between primary hypothyroidism and precocious puberty secondary to ovarian hyperstimulation has been recognized for over a century. Here, we report the case of a 9-year-old girl with severe primary hypothyroidism, who presented with premature menarche, enlarged pituitary gland, enlarged ovaries with multiple cysts, and elevated prolactin and α-feto protein levels. Pituitary and ovarian radiology findings, and α-feto protein levels normalized a few weeks after hypothyroidism treatment was started. Reviewing the literature we found several reports of increased levels of tumor markers in girls with this association. Thyroid function tests should be always part of the evaluation of patients with precocious puberty especially if the bone age is delayed. Tumor markers and liver function tests may be abnormal in patients with severe hypothyroidism and improve soon after thyroid hormone replacement is started.

Familial hypercholesterolemia (FH) is an autosomal dominant, inherited disease (OMIM 143890) characterized by elevated serum cholesterol bound to low-density lipoprotein (LDL). It is mainly caused by mutations of the low-density lipoprotein receptor gene ( LDLR ). In this study, we investigated two Chinese pedigrees with FH. The probands were a 9-year-old boy and a 1-year-old boy, who had high LDL-C levels. The proband in family A showed skin xanthoma. We sequenced the promoter and all exons and exon-intron boundaries of the LDLR gene to detect potential mutations. Compound heterozygote of c.1747C>T and c.2054C>T was detected in the proband of family A, and a heterozygous indel mutation c.551_553 delGTAinsTT was discovered in the second family. The c.1747C>T and c.2054C>T mutations, which have been reported previously, result in His583Tyr and Pro685Leu substitutions, respectively. The novel c.551_553 delGTAinsTT indel mutation causes a frameshift, which results in a p.Cys184Phe fs21X mutation in the corresponding protein.

Objective: The objective of this retrospective study was to describe the health status of children with type 1 diabetes mellitus (T1DM) in foster care. Research design and methods: A retrospective chart review of children with T1DM in foster care at the Children’s Hospital at Montefiore (CHAM) in Bronx, NY, USA, was performed. Results: All patients were either African American or Hispanic and raised by single mothers. The majority of referrals were for medical neglect. The time spent in foster care ranged from 1 to 7 years, with 1–12 placements. Only two children were reunified with their biological mothers. Extensive financial burdens on the health-care system for children with diabetes including prolonged hospitalizations awaiting placement, frequent hospital admissions, and support services were noted. Conclusions: To our knowledge, this is the first report on children with T1DM in foster care. Poor glycemic control and suboptimal social outcomes were noted in the children we report in our case series. Programs geared to improve and reform foster care for children with diabetes are needed.

The clinical case described in this paper deals with a young female patient affected by primary hyperparathyroidism caused by an ectopic parathyroid adenoma of a supernumerary intrathymic parathyroid. The patient had hypercalcemia, in association with increased levels of parathormone, but was otherwise asymptomatic. Genetics tests for mutation of the MEN1, HRPT2, and CaSR genes were negative. She therefore underwent laboratory and instrumental tests but localization results in the neck were negative – only an intrathymic nodule was visualized. The complete surgical ablation of the thymus was conducted, which highlighted a nodule that, at histological examination, was shown to be an adenoma of a fifth parathyroid gland. The existence of a fifth, hyperfunctioning, intrathoracic parathyroid appears to be a rare cause of primary juvenile sporadic hyperparathyroidism. This peculiar clinical case could be of interest in similar cases evaluated by other surgeons.

Sturge–Weber syndrome (SWS) is a rare disorder involving central nervous system abnormalities. It manifests with a facial port-wine birthmark and a vascular malformation of the brain. Infants and children present with seizures and stroke-like episodes with focal neurologic deficits. Patients with Sturge-Weber syndrome carry the additional risk of developing hypothalamic- pituitary dysfunction, secondary to their central nervous system dysfunction. Although one would suspect the hypothalamic-–pituitary axis would be at risk for impairment given the abnormalities that often occur in Sturge-Weber syndrome, they are not commonly recognized by clinicians. Increased awareness of this potential complication in patients with this rare disease of Sturge-Weber syndrome is needed. We hereby report a case of SWS with partial hypopituitarism and consider it to be important that these patients should undergo routine evaluation of pituitary function in the face of any relevant clinical manifestations.

Evaluation of growth hormone (GH) deficiency often involves use of agents that stimulate GH secretion, such as clonidine, glucagon, insulin, levo-dopa or arginine hydrochloride. We present three pediatric cases of benign, macroscopic hematuria in children without pre-existing renal disease following GH stimulation testing with clonidine and arginine hydrochloride. In all cases hematuria resolved spontaneously within 3–4 days without any intervention. This suggests that careful observation in such cases is sufficient and additional costly evaluation may be avoided. Other than six anecdotal cases registered via on-line adverse event reporting system (AERS), this is the first published report to date of painless, macroscopic, self-limiting hematuria after arginine hydrochloride infusion.

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive inborn error of mitochondrial fatty acid oxidation. It is caused by rare mutations as well as polymorphic susceptibility variants. We describe here the case of a 1-year-old male patient who had growth and mental retardation, seizures, and recurring fever since infancy. Urinary gas chromatography/mass spectrometry (GC/MS) showed elevated levels of ethylmalonic acid. Plasma acylcarnitines on tandem mass spectrometry (MS/MS) and elevations of C4-cartinitine are consistently present. The two polymorphic susceptibility variants of the short-chain acyl-CoA dehydrogenase (SCAD) gene, c.625G>A and c.322G>A, were detected. Because of its highly variable clinical characteristics, there are no related reports in China. This report broadens the phenotype and genotype of SCADD in China and underlines the difficulty of diagnosis.

X chromosome aneuploidy has been identified as a potential risk factor for the development of neuroblastic tumors. We report a case of a 4-year-old girl with a 45,X karyotype incidentally discovered to have a large ganglioneuroblastoma on initial screening ultrasound. The incidence of these tumors in girls with Turner syndrome as well as their possible relationship to recombinant human growth hormone treatment is discussed.

Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant inherited disease caused by heterozygous inactivating mutations in the glucokinase ( GCK ) gene and is characterized by mild non-insulin-dependent fasting hyperglycemia. It is treated with diet only, and complications are extremely rare. We present a report of a family with MODY2 caused by a novel NM_000162.3:c.878T>C mutation in exon 8 of the GCK gene. Testing for MODY2 and reporting all novel mutations are important to avoid difficulties in the interpretation of genetic test results and to provide fast and definitive diagnosis for all patients with this disease.

Homozygous mutations in the glucokinase gene ( GCK ) result in a complete deficiency of the GCK enzyme, which leads to permanent neonatal diabetes mellitus. Whilst there has been one report of a patient (with a homozygous p.T168A) who was diagnosed with diabetes at the age of 2 months, all other cases were diagnosed with diabetes within the first 2 weeks of life. We now report a second unrelated patient with the same p.T168A GCK mutation who was diagnosed with diabetes at the age of 9 months. We conclude that the specific GCK mutation, as yet unidentified genetic modifiers, and/or environmental factors might have different effects on pancreatic β-cell functions, causing variability in the age at diagnosis of diabetes.

No abstract available.

No abstract available.