Volume 24, Issue 9-10

No abstract available

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs.

Intracranial hypertension (IH) is a rare condition in children. However, a relationship between recombinant human growth hormone (rhGH) therapy and IH has been well documented. Risk factors were assessed for 70 rhGH-naive patients enrolled in the National Cooperative Growth Study with reports of IH after treatment initiation. Patients with severe growth hormone deficiency, Turner syndrome, chronic renal insufficiency (CRI), and obesity (particularly in the CRI group) were at highest risk of developing IH during the first year of therapy, suggesting initiation of careful early monitoring. In some patients, factors such as corticosteroid use or other chromosomal abnormalities appear to confer a delayed risk of IH, and these patients should be monitored long-term for signs and symptoms of IH.

The primary purpose of this study was to test whether recombinant human growth hormone (rhGH) supplementation would enhance protein synthesis and accretion of lean body mass. Eight adolescents (six males and two females; 17.2±2.6 years; age range, 13.7–21.2 years) participated in a randomized double-blind placebo-controlled cross-over trial of rhGH. We employed stable isotopes to measure proteolysis and protein synthesis during fasting and fed conditions during two 6-month treatment conditions. We also measured bone mineral density (BMD), markers of bone turnover, and body composition. Whole-body proteolysis, phenylalanine catabolism, and protein synthesis did not differ during treatment with rhGH vs. placebo. Enteral nutrition suppressed proteolysis and increased protein synthesis similarly during placebo and rhGH treatments. We conclude that rhGH is unlikely to provide sufficient metabolic benefit to warrant its use as an adjunct treatment in clinically stable adolescents with Crohn disease. A high prevalence of vitamin D deficiency and suboptimal BMD existed, which deserves further investigation and clinical attention.

To evaluate whether through gene transfer, which growth hormone (GH) isoform can influence the circulation IGFBP-3 level, mice were injected three times with the human cytomegalovirus (CMV) mediated mammalian expression vector encoding different GH isoform gene. Then blood samples were drawn and the ELISA method was used to determine the circulation concentration of IGFBP-3. It was found that the 22 kDa GH gene could increase IGFBP-3 levels to 1.94 μg/mL whereas 20 kDa GH, 17 kDa GH and 5 kDa GH genes did not play a role in the circulation expression of IGFBP-3.

Background: Children with growth hormone deficiency (GHD) have increased renal phosphorus reabsorption during rhGH therapy, Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for this effect. Methods: Prospective study in GHD children investigating changes in plasma C-terminal FGF23 (C-FGF23), markers of mineral metabolism, and insulin-like growth factor (IGF-1) in the first year of rhGH therapy. Normal stature children served as baseline controls. Results: The two groups at baseline were similar, except GHD patients had lower baseline TmP/GFR vs. controls (p<0.05). C-FGF23 in GHD patients trended upward at follow-up 1 (p=0.058) and significantly increased at follow-up 2 (p=0.0005) compared to baseline. TmP/GFR also rose at follow-up 1 (p=0.002) and follow-up 2 (p=0.027). The C-FGF23 rise persisted after adjusting for age, gender, sex, total calcium, and phosphorus (p<0.01) but attenuated after adjusting for TmP/GFR or IGF-1. Conclusions: C-FGF23 rises during rhGH therapy in spite of increased Tmp/GFR, an unanticipated observation given the role of FGF23 as a phosphaturic factor. The C-FGF23 rise may be a secondary response during rhGH therapy.

Background: The study aim was to compare somatic development, body composition, insulin growth factor-1 (IGF-1) serum concentration and serum lipid profile between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) 7-year-old extremely low birth weight (ELBW) children and full-term (FT) controls. Materials and methods: Fifty-seven AGA ELBW children [mean birth weight (BW) 850 g and mean gestational age (GA) 26.4 weeks] and 24 SGA ELBW children (mean BW 833 g, mean GA 29.5 weeks) were evaluated. The control group included 37 age- and sex-matched FT children from one outpatient center. Results: Nine AGA and four SGA were found to have short stature defined as height <3rd percentile for chronological age (p=0.9). In the AGA cohort, the results of weight, head circumference, triceps skin fold and body mass index (BMI) measurements were significantly reduced in the short-stature subgroup. IGF-1 serum concentrations differed significantly between short-stature and normal-stature subgroups (121 vs. 193 ng/mL; p=0.02). In the SGA cohort, weight and serum concentrations of total cholesterol (5.03 vs. 4.26 mmol/L; p=0.04), LDL cholesterol (3.24 vs. 2.38 mmol/L; p=0.01) and IGF-1 (113 vs. 211 ng/mL; p=0.01) differed significantly between the short-stature and normal-stature subgroups. Conclusions: Short stature at the age of 7 years was diagnosed in a similar percentage of AGA and SGA former ELBW infants. In both cohorts short-stature children have significantly lower weight and serum IGF-1 levels. IGF-1 seems to be involved in prolonged growth restriction among ELBW infants, regardless of whether they were AGA or SGA.

Purpose: We investigated the effects of clinical and laboratory properties at the time of the initial application of patients recently diagnosed and presenting metabolic indicators of diabetic ketoacidosis who were given disease prognoses in years 1 and 2 after discharge. Materials and methods: A total of 94 patients admitted to Bakirkoy Maternity and Children's Diseases Training and Research Hospital with diabetic ketoacidosis and recently diagnosed with type 1 diabetes mellitus were investigated. Patient files were examined within 2 years following discharge. Findings: All 94 study patients (53.2% male and 46.8% female) presented acidosis, ketonuria and hyperglycemia. While a moderate correlation was detected between the prodromal period and HbA1c values in year 1, only a slight correlation was seen in HbA1c values in year 2. In addition, a slight correlation was observed between the prodromal period and the number of hospitalizations due to diabetic ketoacidosis in the first year. Again, while a moderate correlation was observed between HbA1c values and the number of hospitalizations due to diabetic ketoacidosis in year 1, only a slight correlation was seen in year 2. The prodromal period was directly proportional to patient age. Results: Hospital admissions may be reduced through appropriate treatment, follow-up and metabolic control of patients with type 1 diabetes mellitus. In addition, we report a relationship between the prodromal period and HbA1c values in type 1 diabetes patients.

The aim of the study was to determine the clinical and biochemical characteristics of type 1 diabetes mellitus (DM) at presentation in children younger than 15 years in Croatia during a 9-year period, with special attention to diabetic ketoacidosis (DKA) incidence. The registered data set comprised blood glucose, pH, serum bicarbonate levels, and clinical symptoms at disease manifestation. During the study period, 692 children were diagnosed with type 1 DM. Polydipsia (96.7%), polyuria (96.05%), and weight loss (82.7%) were the most frequent symptoms anticipating disease detection. Enuresis was recorded in 11.55%. A total of 36.41% patients had DKA (pH<7.3) at disease onset. During the 9-year period, the percentage of children presenting with DKA at time of diagnosis decreased from 41.67% to 33.33% (z=1.68, p=0.046). A positive family history of DM, the only factor with an impact on the DKA incidence rate in our population, lowers the probability of the development of ketoacidosis. This study confirms the importance of the detection of the classic symptoms of polyuria, polydipsia, and weight loss in patients with new-onset type 1 DM. The percentage of patients with DKA at diabetes onset decreased during the observed period but is still high and includes one-third of all patients. This is why in every acutely ill child, especially at a younger age, one should evaluate the possibility of type 1 DM to avoid the development of ketoacidosis.

Aims: There is growing body of evidence that oxidative stress plays an important role in the pathogenesis of diabetes mellitus (DM) and in development of maternal and fetal complications of diabetic pregnancies. The aim of the present study was to investigate total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in infants of diabetic mothers (IDM) and to reveal the influence of maternal hyperglycemia on these parameters. Methods: A prospective controlled study was conducted between March 2010 and November 2010. Umbilical cord blood was taken from IDM and controls for TAC and TOS measurement, and OSI was calculated. IDM were divided into two groups, either of mothers treated with insulin during pregnancy or of those treated with a carbohydrate-restricted diet. Results: Thirty-six IDM and 14 infants born to non-diabetic mothers were enrolled. Infants of insulin-treated mothers (group 1) and infants of mothers managed with a carbohydrate-restricted diet (group 2) had significantly higher TOS (p<0.001 and p=0.001, respectively) and OSI (p<0.001 and p=0.001, respectively) levels compared to controls. However, TAC levels were similar in all three groups. Maternal HbA 1c values were correlated to TOS (p<0.001, r=0.694) and OSI (p<0.001, r=0.683). Conclusions: Oxidative stress is increased in IDM, and a significant relation exists between the degree of maternal hyperglycemia in pregnancy and oxidative stress in the newborn at birth.

Background: Magnesium, the second most abundant intra­cellular cation, plays a major role in regulating insulin effect and insulin mediated glucose uptake. It has been shown that serum magnesium levels were negatively correlated with HOMA-IR (homeostasis model of insulin resistance) index. Aim: To investigate the relationship between serum magnesium levels with obesity and insulin resistance in childhood. Methods: Two hundred and three children and adolescents (117 obese children and 86 controls) were included. Obese cases were also subgrouped according to the presence or absence of insulin resistance (IR) as “IR (+) obese” and “IR (–) obese”, respectively. Serum glucose, insulin and magnesium levels were measured after a 12-h fasting at 8–8.30 a.m. We assessed insulin sensitivity by using HOMA-IR index as a surrogate marker of insulin resistance. Results: Serum levels of magnesium were significantly lower in the IR (+) obese group than controls (p=0.014). At the same time, there was a positive correlation between serum magnesium levels and body mass index-standard deviation score (BMI-SDS) (r=–0.28, p=0.03) in the IR (–) obese group. Conclusions: Low serum magnesium levels may contribute to the development of insulin resistance in obese children.

Fulminant type 1 diabetes has recently been identified as a new subtype of idiopathic diabetes that is mostly found in Japanese adults. The aim of this study was to investigate the frequency as well as the clinical and laboratory characteristics of fulminant type 1 diabetes among Korean children with childhood-onset type 1 diabetes. One-hundred and fifty patients that had been newly diagnosed with type 1 diabetes over the past 10 years were included. These patients came from three hospitals. Out of the 150 patients, two female patients fulfilled the criteria for fulminant type 1 diabetes. They were negative for islet autoantibodies. The patients with fulminant type 1 diabetes had an older age of onset and a lower HbA1c than the patients with autoimmune or idiopathic type 1 diabetes. In addition, the patients with fulminant type 1 diabetes had increased serum aspartate aminotransferase, alanine aminotransferase and amylase levels, and decreased fasting serum C-peptide levels. The frequency of fulminant type 1 diabetes was 1.33% among all patients newly diagnosed with type 1 diabetes under the age of 16. Although this type of diabetes is more commonly an adult-onset disease, it is possible that fulminant type 1 diabetes has not yet been fully recognized in children and adolescence, and may be more common than initially thought.

Background: Retinol-binding protein 4 (RBP4) has been proposed as an early marker for insulin resistance (IR), but no prior studies have addressed RBP4 in an exclusively prepubertal population. Children with premature adrenarche (PA) are at increased risk for IR and metabolic syndrome (MeS); thus finding an appropriate early marker for IR in this population would allow for early intervention and prevention of morbidity related to IR and MeS. Objective: To determine whether prepubertal children with PA have higher levels of RBP4 than controls and whether RBP4 correlates with comorbidities of metabolic disease in prepubertal children. Subjects: This study comprised 49 prepubertal children (24 with PA and 25 control subjects), 20 boys and 29 girls, who were between the ages of 5 and 9 years. Methods: This was a cross-sectional, case-control study conducted in a subspecialty ambulatory clinic based in a quaternary care center. RBP4 levels, hormonal values, lipids, and response to an oral glucose tolerance test were evaluated in children with PA and controls, and body composition measures were obtained in a subset of patients (n=18). Results: RBP4 correlated with triglycerides (r=0.57, p<0.0001) but did not correlate with IR in a body mass index z-score-adjusted Pearson correlation analysis. There was no difference in RBP4 levels between the PA and control groups. Conclusions: These findings suggest that RBP4 may be an early marker of dyslipidemia, which may herald future onset of hepatic IR, polycystic ovary syndrome, and MeS.

Background: In the present study we investigated the effect of television watching and the use of activity-promoting video games on energy expenditure in obese and lean children. Methods: Energy expenditure and physical activity were measured while participants were watching television, playing a video game on a traditional sedentary video game console, and while playing the same video game on an activity-promoting video game console. Results: Energy expenditure was significantly greater than television watching and playing video games on a sedentary video game console when children played the video game on the activity-promoting console. When examining movement with accelerometry, children moved significantly more when playing the video game on the Nintendo Wii console. Conclusion: Activity-promoting video games have shown to increase movement, and be an important tool to raise energy expenditure by 50% when compared to sedentary activities of daily living.

Background: Screening for acanthosis nigricans (AcN) in overweight children is repeatedly recommended. The significance of AcN, and its relation to central obesity in children, is unclear. Objective: To compare clinical and anthropometric parameters associated with adiposity, between overweight and obese children with and without AcN. Methods: One hundred and forty-nine overweight and obese children were screened for AcN. Height, weight, waist and hip circumferences, triceps skinfold thickness and segmental body fat amounts were measured. Results: Twenty-two (14.8%) children had AcN. Children with AcN had greater height, weight, BMI, waist circumference, waist-to-height-ratio, triceps skinfold thickness, and total and truncal body fat percentage, compared to those without AcN. After adjustment for age and BMI, no adiposity measure was increased in children with AcN. Conclusion: Overweight and obese children with AcN basically have greater overall and central adiposity, than those without it. Adjusting for BMI, there is no evidence for increased abdominal fat in these children.

Antiepileptic drugs (AED) had an effect on bone metabolism in children. This study was conducted in order to determine the relationships between serum leptin levels, bone mineral density (BMD) and bone turnover markers in epileptic children. Fifty-three patients were treated with valproic acid (VPA) and 23 with carbamazepine (CBZ) monotherapy; 50 healthy children were included in the study as controls. Serum alkaline phosphatase (ALP) and cross-linked C-telopeptide (CTx) levels were statistically signifi cantly higher in the CBZ group than in the VPA group and the control group (p<0.0001, p<0.010, respectively). Serum osteocalcin and ALP levels were signifi cantly lower in the VPA group than in the control group (p<0.012, p<0.030, respectively). Although we found slightly higher serum leptin levels in both the CBZ and VPA groups, they were not signifi cantly different from the control group (P>0.05). We demonstrated that the markers of bone formation and resorption increased with CBZ and decreased with VPA treatment without affecting BMD and vitamin D levels in prepubertal epileptic children.

Objective: To examine the associations between morning cortisol and adiposity in children at baseline and 9-month follow-up. Methods: Participants included 649 (301 males, 348 females) children (9.6±0.9 years) for the cross-sectional analysis and 316 (153 males, 163 females) for the longitudinal analysis. Body mass index (BMI, kg/m 2 ) was calculated from measured height and weight and waist circumference (WC, cm) was measured at the superior border of the iliac crest. Cortisol was assessed via saliva samples collected on a single morning. Cross-sectional and longitudinal analyses were conducted to examine the relationships between cortisol and adiposity. Results: Approximately 31% were overweight (17.7%) or obese (12.8%). The mean cortisol level was 9.36±5.64 nmol/L (0.34±0.20 μg/dL). At baseline, no significant correlations were found between cortisol and BMI or WC (r<0.07). Baseline cortisol did not correlate with change in BMI z-score (r=–0.03) or WC (r<–0.01) over the follow-up period. When examined by weight status, baseline cortisol was significantly related to changes in WC (r=0.32) and BMI z-score (r=0.28) among overweight subjects. Conclusions: A positive relationship was found between morning cortisol and change in WC over 9 months in overweight children. Future studies should examine the association between 24-h cortisol patterns and direct measures of trunk fat.

Hyperinsulinemia increases the risk of cardiovascular disease in obese children. Only a few treatments are available to decrease insulin resistance. The reduction of hyperinsulinemia by dietary means would be a simple, physiologic and economic way to reduce the risk of metabolic disease. Objective: To compare the effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic adolescents. Materials and methods: Eighty-six randomly assigned insulin-resistant obese adolescents completed a 16 week calorie-restricted diet. The experimental diet had a reduced glycemic index designed to evoke a low insulin response (LIR), with carbohydrates and proteins ingested in separate meals. The control diet was a conventional (CD) with similar proportions (60%, 20% and 20%). Variables studied were blood glucose and insulin concentrations after an oral glucose load, body mass index, waist circumference, and insulin resistance (homeostasis model assessment, HOMA). Results: Mean weight [±Standard Deviation (SD)] was significantly reduced after the LIR (–0.53±0.5) and the CD (–0.54±0.4), but a greater decrease of waist circumference (cm) was observed after the LIR (–9.1±4.8 vs. –6.6±4.6, p=0.02). Fasting insulin concentrations (–17.9±27.9 vs. –9.4±14.8, p=0.01) and HOMA dropped significantly more after the LIR than after the CD (–3.5±4.9SD vs. –2.4±1SD, p<0.0001). Conclusions: The LIR diet reduces serum insulin concentrations and waist circumference more than conventional treatment and appears to be a promising alternative to a conventional diet in insulin-resistant obese adolescents. Long-term follow-up is needed to evaluate the maintenance of weight loss and metabolic parameters.

Objective: The aim of this study was to evaluate early cardiac abnormalities in obese children by the conventional echocardiography and to verify whether N-terminal pro B-type natriuretic peptide (NT-proBNP) differ between obese and healthy children. Methods: We started this study with 68 obese children and 35 healthy controls matched for age and sex. Body mass index (BMI) was calculated. Children with a BMI≥95th percentile were considered obese. Thirty children in the obese group were also diagnosed with metabolic syndrome, according to the International Diabetes Federation criteria. Standard echocardiographic study was performed on each patient and control subject. Diastolic filling parameters were evaluated using pulsed-wave tissue Doppler method. Blood samples were taken at 8 a.m. to study blood biochemistry tests, including insulin, lipids, glucose, and NT-proBNP. Serum NT-proBNP levels were measured by a solid-phase, enzyme-labeled chemiluminescent immunometric assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Children with HOMA-IR >3.16 were considered insulin-resistant. Results: There were diastolic filling abnormalities in obese children, as shown by a decreased mitral valve early filling (E) wave/late filling (A) ratio and a prolongation in E-wave deceleration time. The levels of NT-proBNP were not statistically different among the groups. The levels of NT-proBNP were not different between obese children with and without metabolic syndrome, those with and without hypertension, and those with and without insulin resistance, respectively. Conclusion: Although there were diastolic filling abnormalities in obese children, their NT-proBNP levels were not different from healthy controls. It seems that there is no diagnostic value in NT-proBNP levels between obese children and healthy controls

Aims: All screening programmes in the UK use a primary thyroid stimulating hormone (TSH) screen for congenital hypothyroidism. Recent attention has been paid to aspects of screening, such as the relation between blood spot TSH levels and birth weight or gestational age. The aim of our study was to determine the factors affecting screening neonatal TSH levels. Methods: We conducted a retrospective analysis of blood spot screening TSH levels of all infants screened at a single regional screening laboratory. Results: There were 6498 infants screened during a 12-week period. Screening TSH level showed negative correlation with gestational age and birth weight. Multiple linear regression analysis revealed low birth weight as the only independent factor affecting screening TSH level. Conclusions: Low birth weight infants appear to be at risk of thyroidal dysfunction. Our study showed that there were clinically significant but weak correlation between higher screening TSH levels and low birth weight. The clinical importance of these findings requires larger prospective studies to further elucidate the relevance of these factors affecting TSH screening levels.

Background: Due to lack of country-specific norms in China, we established the reference range of plasma amino acids for younger Chinese children by reverse phase high-performance liquid chromatography (HPLC). Methods: Plasma proteins were precipitated with ethanol. L-Norvaline served as an internal standard. This HPLC method was based on automated precolumn derivatization using o -phthalaldehyde 3-mercaptopropionic acid for primary amino acids and 9-fluorenylmethyl chloroformate for secondary amino acids. Twenty-three amino acid derivatives were separated by a Zorbax Eclipse AAA column and detected fluorometrically. Plasma amino acids were measured in 108 healthy Chinese children (ages 0–5 years, 59 boys and 49 girls). Results: The assay was linear from 7.2 to 925.0 μmol/L for all amino acids. Recovery of amino acids added to plasma samples was 93%–107%. Within- and between-run reproducibility was 0.18%–6.27% and 2.94%–16.15%, respectively. Sex- and age-specific plasma amino acid reference range for younger Chinese children was established. In our study, the boys had significantly higher levels of glutamine, citrulline, and tryptophan than girls (p<0.05), and the girls had a significantly higher level of alanine than boys (p<0.05). Compared with the 0- to 1-year group, the 1- to 5-year group had significantly higher levels of citrulline, valine, phenylalanine, isoleucine, and sarcosine and lower levels of aspartate, glutamate, serine, threonine, alanine, methionine, and tryptophan (p<0.05). Conclusions: This study validates the HPLC method described here as a simple, rapid, and reliable assay. The reference range of plasma amino acids for younger Chinese children is different from that for Caucasian children and will facilitate our clinical diagnosis in the future.

Epithelial solid tumors which are rare in childhood are responsible for about 9% of all childhood cancers. However, differentiated thyroid carcinomas (DTCs) are the most common of the endocrine neoplasia (0.5%–3%) in all childhood malignancies. Pediatric thyroid cancers have some clinicopathological differences from adult thyroid cancers. This analysis investigates the clinical behavior and pathological characteristics of childhood thyroid cancers, with treatment options and outcomes. A total of 26 patients who had been diagnosed as having differentiated thyroid cancer when they were younger than 18 years old, and who took radioiodine ablation treatment, were included in this analysis. The incidence of multifocality, capsule invasion and lymph node metastasis were calculated as 11.5%, 42.3% and 53.8%, respectively. At the 6th month, an absence of I-131 uptake in the neck, with a serum thyroglobulin (Tg) level <1 ng/mL in the T4 off state, was accepted as the criterion for ablation of thyroid remnant. The mean follow-up period was 20.4 months (range 6 months–5 years). As a result, 19 patients were ablated with a single dose of I-131 (2–4 GBq). A total of 6 patients took a second dose of radioiodine treatment for lymph node or distant metastases. One of these patients was 6 years old and had recently received ablation. He had diffuse lung metastasis, which was detected on the 6th day post ablation with whole body scintigraphy, and he is now under follow-up. Successful surgery and an effective radioiodine ablation have a crucial role in good outcomes of childhood DTCs.

To review our Pediatric Endocrinology Division’s experience with differentiated thyroid carcinoma (DTC) we analyzed retrospectively the records of patients with DTC that had been seen between June 1988 and June 2008. Results: Forty-five patients (median age 13.7 years, 36 female) were diagnosed (papillary: 40, follicular: 5) with DTC presenting as a solitary nodule (n: 25), thyroid nodule with cervical adenopathy (n: 9) and multinodular goiter (n: 11). All underwent total thyroidectomy with resection of suspicious cervical lymph nodes (CLN). DTC was multicentric in 59% and revealed extrathyroidal extension in 44%. Initially, 44% had CLN metastases and 24% distant metastases. All patients underwent thyroid remnant ablation with 131 I and suppressive treatment. Median follow-up was 5.1 years with a disease-free survival rate at 5 years of follow-up of 75%. Eleven percent presented recurrences. Conclusion: Pediatric DTC has an aggressive behavior at presentation. Higher preoperative TSH levels were significantly associated with a more advanced disease at diagnosis. CLT was present concomitantly in a quarter of the patients and further studies are needed to establish differences in these patients’ outcome. Diagnostic approach, total thyroidectomy, 131 I treatment and thyrotropin suppression allowed a good progression-free survival rate.

Fanconi-Bickel syndrome (FBS) is a rare inherited disease caused by mutations in the glucose transporter 2 gene, SLC2A2 . We reported the first two Chinese cases of FBS. Both cases presented typical clinical features of hepatomegaly, hypophosphatemic rickets, severely stunted growth, fasting hypoglycemia along with postprandial hyperglycemia, and proximal renal tubular dysfunction with disproportionately severe glucosuria. Genetic analysis of SLC2A2 gene revealed novel compound heterozygous mutations in both patients. The characteristics of being born as small for gestational age and apparent liver dysfunction in our cases have been seldom discussed in the literature. It seems FBS patients in general have lower birth weight than normal, but further data collection is still needed. Symptomatic treatments were effective, but the serum transaminase of patient 2 remained moderately increased, and he patient needed further follow-up. The present study will supplement the up-to-date clinical characteristic spectrum for FBS.

Fanconi’s syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and a child mainly presents with dehydration and hypernatremia. We report the first case of idiopathic Fanconi’s syndrome along with nephrogenic diabetes insipidus (NDI) in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi’s syndrome. We hypothesized that the NDI may be due to severe hypokalemia induced tubular dysfunction. The child was treated for hypophosphatemic rickets with severe metabolic acidosis and the treatment for NDI was also given. Now he has healed rickets and normal blood pH, sodium and osmolarity.

The objective of this short communication was to evaluate the roles of reputation and objective measures in U.S. News rankings of the top 50 children’s hospitals for diabetes and endocrinology. Analysis was performed on data obtained from the 2011 to 2012 report. Reputation scores exhibited more variance (CV=158%) compared to objective measures (average CV=14%). Ranking hospitals based on reputation, compared to total score, identified the same top hospital, same top five hospitals, and 90% of the same top 10 hospitals. Ranking based on total objective score resulted in different top hospitals, 60% of the same top five hospitals, and 50% of the same top 10 hospitals. Hospital total rank was strongly associated with reputation rank ( ρ 2 =0.78) and moderately associated with objective rank ( ρ 2 =0.48). Objective rank was minimally associated with reputation rank ( ρ 2 =0.19). Among the top 50 children’s hospitals in diabetes and endocrinology, standings reflect reputation more than objective measures.

Heterozygous activating mutations in the KCNJ11 gene can cause permanent and transient neonatal diabetes. In the present study, we sequenced the KCNJ11 gene in a Chinese boy diagnosed with permanent neonatal diabetes mellitus (PNDM) and also in his parents. A heterozygous 175G>A (V59M) mutation was identified in the patient, while no KCNJ11 gene mutations were found in his parents, indicating that this mutation is de novo. The patient with the V59M mutation successfully switched from insulin injections to oral glibenclamide; 2 years of follow-up revealed that the patient had intermediate developmental delay, epilepsy and neonatal diabetes (DEND) syndrome. This is the first patient who is reported to have iDEND syndrome due to KCNJ11 V59M mutation in China.

Congenital hypopituitarism is commonly diagnosed either in infancy with neonatal hypoglycemia, prolonged jaundice and/or microphallus or in early to mid-childhood because of short stature. Replacement of deficient hormones allows the affected children to have a normal and productive life. We describe a 10-year-old boy with congenital hypopituitarism whose parents first sought definitive medical attention when the child developed congestive heart failure due to dilated cardiomyopathy, presumably secondary to prolonged untreated central hypothyroidism and growth hormone deficiency.

Pituitary abscess is a rare but potentially life-threatening infectious process. Diagnosis is challenging as symptoms are non-specific and signs of infection may be absent. We report the case of a previously healthy 17-year-old male who presented with worsening headaches, polyuria, polydipsia and no clinical signs of infection. On evaluation, he was found to have hypopituitarism with diabetes insipidus, hypothyroidism and adrenal insufficiency. An imaging study revealed a pituitary mass. He underwent transsphenoidal biopsy to rule out tumor. The abscess was drained transsphenoidally and he was treated with parental antibiotics. Magnetic resonance imaging one year later revealed a normal pituitary without any evidence of abscess or mass. He continues to require thyroid, adrenal and anti-diuretic hormone replacements. As with any pituitary lesion, prompt complete hypothalamic pituitary evaluation is essential to avoid potentially life-threatening consequences.

Blastomyces dermatitidis is a dimorphic fungus that can cause granulomatous lesions. Typically, children present with respiratory symptoms. Central nervous system involvement is unusual, and almost always associated with involvement of other organs. This case report, to our knowledge, is the first published case of an adolescent male presenting with panhypopituitarism secondary to a blastomycosis infection.

Objective: There are many genes reported to have been associated with combined pituitary hormone deficiencies, but mutations in HESX1 strongly correlate with septo-optic dysplasia. Our aim was to determine the cause of panhypopituitarism in our patient. Patients and methods: We studied an 8-month-old child having panhypopituitarism. The coding exons of PIT1, PROP1, LHX3 , and HESX1 genes were amplified. Direct sequencing was done after denaturing HLPC. Results: We identified a novel homozygous mutation (R160H) within the homeodomain of HESX1 , which, to our knowledge, is the first to be described in humans. Neuroimaging studies revealed anterior pituitary aplasia, a normal posterior pituitary gland, and a thin pituitary stalk but no midline abnormalities. Optic nerve studies showed no pathology. This mutation is also carried in the parents of the affected child in a heterozygous pattern, suggesting an autosomal recessive inheritance. Conclusion: These data demonstrate that homozygous HESX1 mutation causing an R160H substitution can result in panhypopituitarism without midline defects.

Poorly differentiated thyroid carcinoma (PDTC) is a rare disease with a poor prognosis in children. We describe a 9-year-old boy with a thyroid nodule composed of cystic and solid components, which became completely solid and hypoechoic and was subsequently proved to be PDTC. The tumor consisted of small- to intermediate-size round cells in a trabecular or insular pattern with hyperchromatic nuclei and mitotic figures. The tumor cells were positive for thyroid transcription factor 1 and thyroglobulin. PDTC is morphologically and prognostically between the well-differentiated and anaplastic carcinomas. It must be distinguished from the solid variant of papillary carcinoma and well-differentiated follicular carcinoma with a predominantly solid/trabecular growth pattern. The tumor stage was T2N0M0. The patient was treated with total thyroidectomy, left-sided neck level VI lymph node dissection, recombinant human thyrotropin-stimulated 131 I ablation therapy, and thyroid-stimulating hormone suppression. Malignancy should be suspected in a cystic thyroid nodule that becomes solid and hypoechoic.

This report describes a case of a neonate presenting with many of the typical phenotypic characteristics of chromosome 3p deletion including hypertelorism, flat nasal bridge, flat philtrum, thin lips and low-set ears. The hands and feet showed post axial polydactyly, single palmar creases and rocker bottom feet. A karyotype confirmed chromosome 3p25.3-pter deletion with normal parental karyotypes. A high TSH was noted on newborn screening and congenital hypothyroidism was confirmed on thyroid function tests. Thyroid nuclear imaging was suggestive of dyshormonogenesis. This is the first reported case of congenital hypothyroidism in an infant with chromosome 3p deletion.

We present a rare case of membranoproliferative glomerulonephritis (MPGN) associated with autoimmune hypothyroidism in a child. The exact pathogenesis of glomerulonephritis remains unclear. Thyroxine replacement therapy along with steroids may lead to significant decrease in proteinuria and resolution of edema. Thyroid status should be evaluated in all cases with MPGN.

Background/aims: Two unrelated patients found to have hereditary vitamin D resistant rickets (HVDRR) were admitted to our hospital. Methods: This article describes the diagnosis, management and molecular basis for their disease. Results: Both patients had severe growth and motor developmental retardation, rickets with chest deformities and pulmonary abnormalities, but no alopecia. Both had hypocalcemia, secondary hyperparathyroidism and susceptibility to pulmonary infections. In both cases, good response with normalization of abnormal biochemistries and healing of rickets was achieved with IV calcium infusion. Subsequently, improvement was maintained with oral calcium. Both children harbored the same unique missense mutation in the vitamin D receptor ( VDR ) gene that substituted arginine with histidine at amino acid 274 (R274H) in the VDR ligand-binding domain (LBD). R274 is a contact point for the 1α-hydroxyl group of 1,25(OH) 2 D 3 , the active ligand for the VDR. Functional analyses of the R274H mutation revealed a 100-fold decrease in activity compared to wild-type VDR . Conclusion: We describe a novel missense mutation at R274H in the VDR gene that resulted in the HVDRR syndrome in two unrelated children. Vigorous treatment using IV calcium to normalize their hypocalcemia achieved dramatic improvement in these complex and severely ill patients.

There are two types of vitamin D dependent rickets (VDDR) that cause rickets in children. Vitamin D dependent rickets type 1 (VDDR-I) is caused by an inborn error of vitamin D metabolism, which interferes with renal conversion of calcidiol (25OHD) to calcitriol (1,25(OH) 2 D) by the enzyme 1α-hydroxylase. Vitamin D dependent rickets type 2 (VDDR-II) is caused by a defect in the vitamin D receptor (VDR). We report cases of two African children affected by VDDR-I and VDDR-II, respectively. Establishing an early diagnosis of these genetic forms of rickets is challenging, especially in developing countries where nutritional rickets (NR) is the most common variety of the disease. A prompt diagnosis is necessary to initiate adequate treatment, resolve biochemical features and prevent complications, such as severe deformities that may require surgical intervention.

Inherited nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to arginine vasopressin (AVP). The most common cause is mutations in the AVP receptor 2 ( AVPR2 ) gene at Xq28. Severe complications of NDI are rare but can occur after severe dehydration without treatment. A 7-year-old boy presented with short stature and severe intellectual disability other than polyuria and polydipsia. The karyotype was normal. Direct sequencing revealed a novel missense mutation c.506T>C (p.L169P) in AVPR2 in the patient. His mother was heterozygous for the mutation. The mutation was absent in 103 unrelated healthy males and predicted to be consistently pathogenic by several prediction methods, including Polyphen, SIFT, PMut, PhD-SNP, SNPs3D, PANTHER, and MEMPACK. Awareness of the primary signs of NDI, polyuria, and polydipsia would facilitate early diagnosis and treatment to prevent its severe complications. Also, molecular analysis will provide a rapid and definitive diagnosis and facilitate genetic counseling for family planning.

Diabetes insipidus (DI) is rare in childhood and has a wide-ranging aetiology including the involvement of uncontrolled proliferation of dendritic cells in the hypothalamic-pituitary axis, characteristic of Langerhans cell histiocytosis (LCH). DI may manifest as a sequela of multisystem LCH disease involving skin, bone, liver, spleen and lymph nodes. In very rare cases patients diagnosed with LCH exhibit neurodegenerative changes, such as severe ataxia, tremor, dysarthria and intellectual impairment. We report a 2½-year-old boy who presented initially with apparent idiopathic DI, developed anterior pituitary hormone deficiency and progressive neurological deterioration secondary to neurodegenerative LCH.

Hypothalamic hamartomas (HH) are rare congenital non-neoplastic lesions of the tuber cinereum, which usually present as precocious puberty of central origin in young girls and respond well to treatment with long acting gonadotropin releasing hormone (GnRH) analogs. No association of this condition with diabetes mellitus of any form has been reported so far. On the other hand, diabetes mellitus in children and adolescents, when it is not autoimmune type 1 diabetes, is difficult to classify. We present a girl with early onset of central precocious puberty at the age of 8 months, due to hypothal-amic hamartoma. Treatment with depot of a GnRH analog for a period of 9 years and 8 months was successful, and her puberty continued 6 months after the discontinuation of triptorelin. At the age of 9 years 6 months, the girl presented with diabetes. She was negative for islet, GAD and IA2 antibodies and her insulinemia and C-peptide remained within normal limits during the 2 years of follow-up. Her metabolic control is excellent with a combination of metformin and a low-dose of mixed insulin. To our knowledge, this is the first description of the simultaneous appearance of these two endocrinological conditions.

This case report describes severe hyperinsulinism in a term newborn infant without typical perinatal risk factors for transient hyperinsulinism. The mother had received bupropion, an antidepressant and aid to smoking cessation, throughout pregnancy. The infant presented with profound hypoglycemia and seizures on the 3rd day of life. Laboratory investigation confirmed hyperinsulinism. Stable euglycemia could be achieved only after starting diazoxide. The infant was weaned from diazoxide by 10 weeks of age without recurrence of hypoglycemia, signifying the transient nature of hyper­insulinism. This is the first reported case of a potential association between maternal bupropion use during pregnancy and neonatal hyperinsulinism, and highlights the importance of close monitoring of similar infants.

The identification and diagnosis of child abuse is a challenging task to the pediatrician. The increased awareness among both the public and medical personnel, while improving attentiveness to this important subject, can sometimes result in misdiagnosing medical conditions, thus causing distress and delay in required treatment. Numerous reports have described conditions mimicking non-accidental injuries; most of these include dermatological findings related to skin diseases, medical conditions causing pathological fractures, and rare diseases with unusual physical findings. We present a case of a 9.5-year-old child in which the workup for a suspected abusive event led to a delay in the diagnosis of insulin dependent diabetes mellitus later presented as diabetic ketoacidosis.

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. Mutations in the BCKDHA , BCKDHB , and DBT gene impair the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex, resulting in the accumulation of branched-chain amino acids and branched-chain alpha-ketoacid in tissues and plasma. This leads to mental and physical retardation, feeding problems, and a maple syrup odor in the urine. In this study, we describe the clinical and biochemical manifestations of a sporadic mutation in a neonate with classic MSUD. Analysis of the BCKDHA gene revealed a compound heterozygous mutation consisting of two novel missense mutations (p.L103P and p.R265P). Viewing the protein with PyMOL indicated that the p.L103P and p.R265P mutations were, respectively, located in the helical region and core domains of the BCKD’s E1a component. The p.L103P mutation affected the hydrophobic cores and is predicted to shorten the helix; the p.R265P mutation can predictably affect the cofactor binding site by ligating the associated manganese ion. In conclusion, we identified two novel missense mutations in the BCKDHA gene in a Chinese patient with MSUD.

Mixed gonadal dysgenesis (MGD) is a form of sex chromosome disorder of sex development with large phenotypic variability. Patients with MGD typically have asymmetric and ambiguous genitalia with a combination of Müllerian and Wolffian duct derivatives. Prenatal androgen exposure results in variable degrees of phallic enlargement and a urogenital sinus. Here, we report an infant with ambiguous genitalia due to MGD. Despite marked evidence of prenatal androgen exposure, there was a completely intact distal vagina.

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies. Association of MAS with GH excess is rare, and in most of the instances somatotropinoma has not been documented. Treatment of patients of MAS with acromegaly is difficult because of thickened calvarium and dysplastic skull bone. We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia, café-au-lait macules and also had acromegaly due to pituitary macroadenoma, and treated with gamma knife radiosurgery.

Background: The leydigioma is the most frequent interstitial neoplasm of the testis. Clinical symptoms of all leydigioma usually are isosexual precocious pseudo-puberty due to autonomous testosterone overproduction, suppressed gonadotropin levels and a testis mass. Nowadays its therapy is debated. Design and methods: We report a case of a young child treated in 2008 for a leydigioma of the testis with atypical clinical behavior. Testicular oncologic markers and hormonal profile were assessed. Results: The patient was treated successfully with organ-confined surgery. Conclusion: We want to confirm the safety of conservative surgery against radical orchiectomy and review the literature of the last decade on this debated matter.

Total parenteral nutrition (TPN) is a revolution in neonatal intensive care unit (NICU) care, but this therapy is not without problems. A 35-week-old, 1300 g female infant was transferred to our NICU because of bilious vomiting and feeding problems. When enteral feeding was started again, a severe condition similar to the previous one developed. On the 24th day, the patient underwent surgery with a diagnosis of Hirschprung’s disease. One week before surgery, the parenteral solutions were composed without vitamins because intravenous vitamin supplements suitable for infants were not available. Thereafter, the patient suffered from severe hypoglycaemia, and sepsis started to develop, accompanied by a large anion gap and metabolic acidosis which is severe lactic acidosis refractory to massive doses of bicarbonate. The acidosis improved significantly when the patient was treated with thiamin. Although TPN is life saving in the NICU, meticulous attention must be paid while treating a patient with TPN, and all possible nutrients should be provided. In this report, a case of a preterm newborn requiring a prolonged period of TPN and complicated by serious lactic acidosis is presented and discussed.

Phenotypic and clinical features of individuals with ring chromosome 18 [r(18)] vary with the extent of deletion of the short (18p-) or long arm (18q-). Most patients with r(18), therefore, demonstrate a clinical spectrum of both 18p- and 18q- deletions. Short stature, microcephaly, mental and motor retardation, craniofacial dysmorphism and extremity abnormalities are the most commonly reported features in patients with r(18). Abnormalities of chromosome 18, especially 18p- syndrome, are often reported with autoimmune thyroid disease and growth hormone deficiency, but reports of endocrine abnormalities associated with r(18) are rare. Here, we report a case of an African-American female with hyperthyroidism, type 1 diabetes mellitus, vitiligo and IgA deficiency associated with a r(18) chromosome complement. This patient additionally had mild intellectual disability and dysmorphic features. Karyotype analysis showed a de novo ring chromosome 18 (deletion 18q23-18qter and deletion 18p11.3-18pter). Although this unique association of autoimmune polyglandular endocrinopathy with ring chromosome 18 could be coincidental, we speculate that a gene or genes on chromosome 18 might play a role in the autoimmune process.

Achondroplasia is the most common type of short-limbed dwarfism in children resulting from fibroblast growth factor receptor (FGFR) mutations. Activating mutations of FGFR3 also result in other forms of skeletal dysplasia and craniosynostosis. Acanthosis nigricans is associated with these skeletal dysplasias and we recently encountered a skeletal dysplasia along with acanthosis nigricans in a young boy. We report the case due its unusual nature affecting one of twin brothers.

High rates of skeletal complications, growth disturbances, thyroid and gonadal dysfunction have been described in children undergoing stem cell transplantation. Although secondary adrenal insufficiency has been diagnosed, no primary adrenal insufficiency has been reported after busulfan and cyclophosphamide (Bu/Cy)-based conditioning regimens for stem cell transplantation in children. A 9-year-old girl with myelodysplastic syndrome was treated with stem cell transplantation of allogeneic origin. She received myeloablative conditioning chemotherapy, Bu and Cy. Her serum cortisol level was normal before stem cell transplantation. Then, 17 months after stem cell transplantation, chronic graft-versus-host disease developed and was treated with methyl prednisolone for 3 months. The control endocrinological investigation revealed low serum cortisol and high serum adrenocorticotropin (ACTH) levels 6 months after completion of methyl prednisolone treatment. The ACTH stimulation test demonstrated primary adrenal insufficiency, and the other etiologies of primary adrenal insufficiency were excluded. The patient received oral prednisolone replacement therapy. She was followed-up for 44 months and required increases in steroid doses during stress periods. Primary adrenal insufficiency which was observed in our patient after Bu/Cy-based conditioning regimen for stem cell transplantation has not been reported in children and adrenal function should be closely monitored in these patients both before stem cell transplantation and after stem cell transplantation.

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