Volume 24, Issue 11-12

No abstract available

Intracranial cysts (ICC) may cause a wide spectrum of endocrinological disorders. We evaluated 27 patients who were diagnosed with ICC during investigation for neuroendocrine dysfunctions and reviewed the relevant literature. The types of ICC in the patients were arachnoid cysts (n=13); Rathke cleft cysts (n=7); pineal cysts (n=5); an ependymal cyst (n=1) and a cavum septum pellucidum cyst (n=1). The neuroendocrine dysfunctions of the patients were obesity (n=7), isolated growth hormone deficiency (n=6), central precocious puberty (n=6), multiple pituitary hormone deficiency (n=3), central diabetes insipidus (n=1), growth hormone deficiency and central precocious puberty (n=1), obesity and galactorrhea (n=1), obesity and hypogonadotropic hypogonadism (n=1) and growth hormone neurosecretory dysfunction (n=1). Only three patients, who had arachnoid cysts, showed neurologic symptomatology. Although three patients underwent surgery, no improvements in endocrinological dysfunctions were observed. ICC should be considered when evaluating patients with endocrinological problems and patients with coincidental ICC should be recommended for follow-up.

Graves’ disease (GD) is the most common cause of hyperthyroidism in pediatric patients. Most pediatric thyroid cancer is differentiated thyroid cancer (DTC). The two diseases can be treated using different methods, such as antithyroid drug, radioactive iodine (RAI), and surgery for GD and surgery and RAI for DTC. RAI can be used to treat pediatric GD and DTC. In the article, we reviewed the RAI application in pediatric GD and DTC.

No abstract available

There is some evidence for elevated thyrotropin (TSH) levels in children born preterm, but follow-up studies into adulthood are lacking. We tested whether thyroid function in young adults born at a gestational age <32 weeks, with either an appropriate (appropriate for gestational age, AGA) or low birth weight for gestational age (small for gestational age, SGA), differed from that in age-matched controls. We made our measurements when the study participants reached 21 years of age. Serum concentrations of TSH and free T4 (fT4) and body composition were measured in subjects born preterm and AGA (n=29) or SGA (n=28), and in non-preterm controls (n=30). The TSH and fT4 concentrations of participants were within normal limits. Free T4 levels in subjects born preterm were slightly higher than those in controls: 17.0±2.4 (AGA) and 17.2±1.7 (SGA) vs. 16.1±1.9 pmol/L (p=0.04). TSH concentrations did not differ between groups. From these preliminary data, we conclude that young adults born preterm have a normal thyroid function.

Background: Severe acquired hypothyroidism often results in significant height deficit due to rapid bone age advancement following treatment. Whether gradual correction of hypothyroidism and/or adjunctive growth-promoting therapies (GPTs) augment final adult height (FAH) is controversial. Objective: To investigate time to euthyroidism, pace of bone age advancement (ΔBA/ΔCA), and impact of GPTs on FAH. Methods and patients: Retrospective review of 21 children (10.1±3.0 years) with profound hypothyroidism. Results: Baseline bone age standard deviation score (SDS) was –4.1±1.8, whereas height SDS was –3.0±1.1. Average time to euthyroidism was 9.7 months (2.3–33.7 months). Average ΔBA/ΔCA was 2.3±0.9. Six of 13 patients at FAH received GPTs. No correlation was found between time to euthyroidism and rate of skeletal maturation. No difference in height outcome was seen between those who received GPTs and those who did not. Conclusions: Neither time to euthyroidism nor use of GPTs significantly affected height potential in our patients.

Context: Hypothyroxinemia in premature neonates may affect long-term neurodevelopment. Objective: This study aimed to examine the effects of hypothyroxinemia of the newborn preterm infants born at 28–36 weeks of gestational age (GA) on the neurodevelopment at 4 years of age. Patients: Prospective observational cohort study conducted in Madrid, Spain. Forty-six preterm infants were included in the study. Main Outcome: The effects of the exposure to neonatal hypothyroxinemia on mental development were examined. Results: Using regression analyses we found that neonatal T4 had a positive association with general cognitive index and Verbal index, and neonatal FT4 with general cognitive and Memory indexes at 4 years of age. Conclusions: The exposure to hypothyroxinemia during the neonatal period of late preterm infants may play role in neurodevelopmental delays. Higher T4 level means a trend to higher indexes and low T4 level means a lower neurodevelopmental indexes at 4 years of age.

Background: It has been suggested that chemotherapy per se might impair the hypothalamus-pituitary-thyroid axis of childhood cancer survivors. Objective: We examined six patients treated for acute lymphoblastic leukemia (ALL) with chemotherapy alone, with suspicious central hypothyroidism (CH). Subjects and methods: ALL was diagnosed at a mean age of 3.8 years (range 0.3–6 years), the mean follow-up is 6 years (range 6–13 years). Auxological data were recorded, and thyroid function, autoimmunity and ultrasonography (US) were evaluated. Three individuals underwent a thyrotropin-releasing hormone (TRH) test and a magnetic resonance imaging (MRI) scan of the hypothalamic-pituitary region. Results: All study participants showed negative thyroid autoimmunity, normal thyroid ultrasound, and thyroid-stimulating hormone (TSH) above the normal range; free T4 (fT4) was abnormally low in two patients. After TRH infusion all patients showed TSH increase and slow TSH decline. Conclusions: Our study shows that CH could arise at any time after childhood leukemia following only chemotherapy treatment. Although overt hypothyroidism was detected in only two patients, a careful follow-up of thyroid function is also recommended for ALL survivors not treated by irradiation.

Background and aim: In the context of present epidemic of childhood obesity, we aimed to fi nd the prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in a cohort of obese children. Methodology: Retrospective chart analysis of 700 obese children was done for their anthropometric and biochemical investigations. Results: Some 15.4% (9.8% girls, 22% boys) subjects had NAFLD (ALT> 40 IU/L) after excluding other identifi able causes of liver dysfunction. Age, weight, TG, fasting serum insulin and HOMA-IR levels were higher in children with NAFLD. Twenty-eight percent children had MS. Children with NAFLD had an odds ratio of 2.65 for having MS (boys 4.6, girls 1.7). The prevalence of MS increased with age 5–9 years (21%), 10–16 years (30%), 17–20 years (35%). Conclusion: Given high prevalence of NAFLD and MS in obese children, childhood obesity should be seriously considered as a disease and not just a cosmetic issue.

Objective: In adults, elevated levels of retinol binding protein 4 (RBP4) have been associated with biochemical markers of adiposity-related co-morbidities including insulin resistance, dyslipidemia, hypertension, and abdominal obesity. This study examined the relationship between RBP4 and risk factors for co-morbidities of adiposity in a population of ethnically diverse children in early- to mid-adolescence in the public school system of New York City. Materials/methods: We analyzed anthropometric (body mass index, % body fat, waist circumference), metabolic (lipids, glucose), and inflammatory (TNF-α, interleukin-6, C-reactive protein, adiponectin) markers for adiposity-related co-morbidities and serum alanine aminotransferase (ALT) in 106 school children (65 males, 41 females) 11–15 years of age (mean±SD=13.0±0.1 years) who were enrolled in the Reduce Obesity and Diabetes (ROAD) project. Insulin sensitivity was assessed by quantitative insulin sensitivity check index. Insulin secretory capacity was measured as acute insulin response and glucose disposal index. Results: Serum RBP4 was significantly correlated directly with ALT, triglycerides, and triglyceride z-score, and inversely correlated with adiponectin. Correlations with ALT and adiponectin remained significant when corrected for % body fat, age, and gender. There were significant ethnic differences in the relationship of RBP4 to ALT, glucose disposal index and adiponectin. Conclusions: In early- to mid-adolescents, circulating concentrations of RBP4 are correlated with multiple risk factors for adiposity-related co-morbidities. The observation that many associations persisted when corrected for % body fat, suggests that RBP4 can be viewed as an independent marker of adiposity-related co-morbidity risk in children.

Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters associated with A-FABP elevation in children and adolescents and to evaluate the effect of obesity intervention and A-FABP diagnostic utility. A-FABP and anthropometric, metabolic, and inflammatory indices were measured in 31 lean and 114 overweight/obese children and adolescents and reassessed after obesity intervention (1 year; diet and enhanced physical activity, with or without metformin). A-FABP was significantly higher in overweight/obese than lean individuals, where it correlated with insulin, waist circumference (WC), and 2-h glucose independent of body mass index (BMI), age, gender, and developmental stage. The pattern of A-FABP associations differed between sexes. As a MetS indicator, A-FABP had 68% accuracy. The weight reduction program was effective in reducing A-FABP, BMI%, WC, triglycerides, and cholesterol. In conclusion, elevation in A-FABP is associated with MetS components independent of BMI status and can be reduced by diet and enhanced physical activity. A-FABP as a single MetS biomarker has a moderate accuracy.

Objective: To examine the prevalence and determinants of obesity and associated cardiovascular risk factors in a sample of Greek children. Methods: This is a cross-sectional, school-based study of 780 students (9.2±1.8 years old, 415 boys) conducted in Eastern Attica, the greater area of the city of Athens. The study protocol included anthropometric, blood pressure (BP), and biochemical measurements, as well as dietary and lifestyle habits assessment. A review of Greek studies on childhood obesity was also performed. Results: Approximately 22% of the participants were overweight and 8% were obese, which is in accordance with the results of 24 previous Greek studies showing the childhood overweight/obesity prevalence in the range of 30%. Overweight/obese children compared with normal-weight children had higher BP, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides (p<0.05 for all). Parental weight, consumption of sweets and fast-food, and decreased physical activity were independent determinants of being overweight/obese. Furthermore, overweight/obesity predicted the presence of high BP, low HDL-C, and high triglycerides. Conclusion: A close association was revealed between obesity and metabolic abnormalities, underlining the need for early screening and intervention in overweight children in order to address the emerging childhood obesity epidemic in Greece.

Background/aim: Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition. Methods: Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids. Results: Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL±0.43) as compared to the others (p<0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 μg/mL±2.4) than in children with TPN (5.8 μg/mL±2.4; p<0.001) and in children hydrated intravenously (3.3 μg/mL±2.3; p<0.001). The concentration of adiponectin correlated significantly with calorie intake. Conclusions: Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants.

Objective: The aim of the present study was to evaluate the effect of oral pentoxifylline on the cross-sectional area of intima media thickness (CSA-IMT) and functions of the common carotid artery, a marker of early atherosclerosis, in adolescents with type 1 diabetes. Patients and methods: Non-invasive ultrasonographic measurements were made in 56 type 1 diabetic patients. The diabetic patients were matched first in terms of age, diabetes duration, major cardiovascular risk factors, including anthropometric and metabolic parameters as well as ultrasonographic measurements, then one individual within each pair randomized into a pentoxifylline group and a placebo (control) group (i.e., 32 on pentoxifylline group and 24 on placebo). Pentoxifylline was administered for 6 months. We investigated the change of CSA-IMT, compliance, distensibility, diastolic wall stress (DWS), and incremental elastic modulus of the common carotid artery at 6 months after pentoxifylline. Results: In comparison of changes in common carotid artery measurements between the two groups, the pentoxifylline treatment group had significantly higher values than the controls for CSA-IMT (–2.6±0.1 vs. 0.7±0.4 mm 2 , p=0.001) and for DWS (–0.38±0.02 vs. –0.05±0.05 mm Hg×10 2 , p<0.001). In a multivariate regression model for all patients, being in pentoxifylline group was the best predictor of the change DWS (β=–0.52, p<0.001). Conclusion: Our preliminary results suggest that pentoxifylline has an antiatherogenic action and might modulate risk factors for atherosclerosis in type 1 diabetes.

Adipose tissue seems to be a pivotal organ in the aging process. We investigated whether healthy aging could have its roots in a sound metabolic condition from the first year of life by evaluating leptin and adiponectin levels in neonates [33 adequate for gestational age (AGA) and 29 small for gestational age (SGA)], 48 centenarians, and 50 healthy elderly subjects. At birth, SGA neonates showed lower leptin levels (SGA 0.88±0.28; AGA 2.22±0.91 ng/mL; p<0.05) and comparable adiponectin levels with respect to AGA. At 1 year, SGA showed increased leptin (SGA 1.74±0.28; AGA 1.31±0.19 ng/mL) and slightly reduced adiponectin concentrations (SGA 35.51±2.53; AGA 38.56±3.18 μg/mL) than AGA. Centenarians showed lower leptin (centenarians 18.71±3.78; elderly 34.81±7.27 ng/mL; p<0.05) and higher adiponectin levels (centenarians 55.63±7.7; elderly 33.51±4.1 μg/mL; p<0.05) than elderly subjects. Centenarians, like AGA infants during the first year of life, show a favorable adipokine profile, suggesting that the metabolic condition at early age could affect the longevity of an individual.

A spectrum of myths and misconceptions about congenital adrenal hyperplasia (CAH) is prevalent among the parents of affected children in India. The perceptions of parents may affect several aspects of these children’s management, and to explore these perceptions we carried out a cross-sectional questionnaire-based descriptive study during May 2010. Twenty-eight individuals (17 males and 11 females), parents of 22 affected children aged <5 years, completed the questionnaire. Their responses showed the prevalence among the parents of misconceptions about CAH. These misconceptions were resulting in potentially harmful practices, and in addition there was immense societal pressure on the families as a result of ignorance and myths about the disorder. There is a need for regular CAH education and interaction programs to provide an acceptable platform for the parents and patients, where their concerns can be expressed and shared and their requirements addressed appropriately by a multidisciplinary team.

We aimed to determine the prevalence and clinical characteristics of non-classical congenital adrenal hyperplasia (NCCAH) with V281L mutation in patients with premature pubarche. An adrenocorticotrophic hormone (ACTH) stimu­lation test was performed in 14 of the 159 patients with premature pubarche (PP). Patients whose stimulated 17α-hydroxyprogesterone (17-OHP) level on the ACTH test was ≥10 ng/mL underwent a mutational analysis of the CYP21 gene. NCCAH was defined in nine (5.7%) patients, all of whom had the V281L mutation. Four of the NCCAH patients were homozygote and four of them were heterozygote. One other patient was compound heterozygote for V281L mutation and the I2 splice mutation. One of the patients with V281L heterozygous mutation developed true precocious puberty and the other one had rapid progressive early puberty and developed polycystic ovary syndrome. ACTH stimulated 17-OHP ≥10 ng/mL in PP patients is load star to mutation analysis and heterozygote patients should be followed for clinical and biological hyperandrogenism up to completion of the whole ‘genome sequence’.

Background and aims: The association between bone turnover markers and bone mass in adolescence is not clear. We aimed to evaluate the associations between bone turnover markers and bone mineral content (BMC), density (BMD) and area (BMA). Subjects: A total of 56 adolescents (25 boys, 12.5–17.5 years) participated in the study. Methods: Bone mass and physical activity (PA) were measured using dual energy X-ray absorptiometry and accelero­meters. Osteocalcin and amino-terminal propeptide of type I procollagen (PINP), as markers of bone formation, and β-isomer of the C-terminal telopeptide of type I collagen, as marker of bone resorption were also measured. Sexual maturation, weight, height and average PA were considered as confounders. Results: Positive correlations (Pearson) were observed among the three bone turnover markers (r=0.7–0.9). Stepwise multiple linear regression analyses showed that PINP was strong and negatively associated with BMC, BMD and BMA in girls, explaining 24.9% of the variance in BMC, 25.6% in BMD and 16.3% in BMA. Conclusion: PINP is a strong predictor of bone related variables in pubertal girls.

Low adolescent peak bone mass is associated with bone problems in adulthood. Our aim was to assess underprivileged premenarchal Indian girls for low bone mineral content and to study the influence of anthropometric, lifestyle factors on bone health. Data on anthropometry, diet, lifestyle, total body bone mineral content (TBBMC), bone area, bone mineral density, and biochemical parameters [parathyroid hormone, vitamin D (25OH-D), calcium, and zinc] were assessed in 214 premenarchal girls (8–12 years). Compared with the Indian reference database, 15.6% girls had TBBMC for age Z-scores below –2 and 37.5% had Z-scores between –2 and –1. The TBBMC for total body bone area Z-scores were below –2 for one fifth of girls, indicating undermineralized bones. Mean rate of increase in TBBMC with age and Tanner stage was lower in our study population (11.6% and 20.7%, respectively) than reference database (14.2% and 33.4%, respectively). Low weight, 25OH-D, and intake of protein, calcium, and zinc adversely affected TBBMC (p<0.05). Many underprivileged premenarchal Indian girls are at risk of achieving low bone mass. Steps to improve underweight, 25OH-D, intakes of protein, calcium, and zinc might improve bone health.

Children with growth hormone insensitivity syndrome (GHIS) who receive insulin-like growth factor 1 (IGF-1) treatment and enter puberty with inadequate height gain are unlikely to reach adult height within the normal range. Final height standard deviation score (SDS) in most treated children is ≤-5. Combining IGF-1 with gonadotrophin-releasing hormone analogue (GnRHa) therapy may help to improve their final height. Three patients on IGF-1 treatment, two with primary GHI and one with secondary GHI, were started on GnRHa therapy at the onset of puberty. Their ages ranged from 6.4 years to 12.9 years at the start of IGF-1 therapy (120 μg/kg twice daily by subcutaneous injection). Gains in height/bone age SDSs under GnRHa therapy ranged from 0 to 0.9. Growth velocity on GnRHa therapy ranged from 4 cm/year to 4.8 cm/year. Bone maturation (measured as change in bone age divided by change in chronological age, ΔBA/ΔCA) decreased after the start of GnRHa therapy. Predicted adult height (PAH) improved in two patients and was maintained in one. Bone mineral density showed gradual improvement from baseline. Treatment with GnRHa resulted in a gain in PAH. Final height results will provide the definite answer on the effectiveness of this combined treatment.

Objective: To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the effectiveness of therapy with recombinant human growth hormone (rhGH) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency (IGHD). Methods: Forty-eight prepubertal children (IGHD=25, ISS=23) treated for at least 1 year with rhGH were included. Insulin growth factor-1 (IGF-I) and NTproCNP serum levels were measured before starting treatment and again 6 months later. Twelve months after starting treatment, all patients were assessed and annual growth velocity (GV), height standard deviation score (HTSDS), and gain HTSDS (ΔHTSDS) were recorded. Results: In the GHD group, positive relationships between GV and change of IGF-I SDS (ΔIGF-I SDS ), GV and change of NTproCNP concentrations (ΔNTproCNP) were found. GH peak value was also positively associated with IGF-I SDS and NTproCNP before therapy and ΔIGF-I SDS and ΔNTproCNP were positively associated. In the ISS group, GV was associated with only ΔNTproCNP. Conclusions: NTproCNP is a novel biomarker of growth as levels increase during growth-promoting treatment. Furthermore, IGF-I is also valuable in evaluating the efficacy of rhGH therapy in short stature patients.

Objective: To report on the effect of growth hormone (GH) treatment on final height (FH) and to describe the insulin-like growth factor (IGF) system, ghrelin, and adiponectin (ADPN) in children with Seckel syndrome. Subjects and results: Four severely growth-retarded Iraqi siblings (two girls and two boys) with Seckel syndrome were referred at ages 16.5, 14.4, 12.4, and 10.4 years. They were born at term, but their growth was retarded and birth weight ranged between 1 and 1.5 kg. The children were healthy and had a normal response to GH provocative test. Long-term GH treatment of the youngest brother and sister increased the FH by 7.2 and 3.4 cm, respectively, compared with their older brother and sister. At FH, body mass index standard deviation scores (BMISDS) ranged from –3.0 to –3.9. Serum levels of immunoreactive IGF-1, bioactive IGF-1, and IGF-binding protein 3 were all within normal to high range before GH treatment and increased after GH treatment. Fasting plasma ghrelin remained severely reduced. Despite low BMISDS, plasma ADPN was moderately reduced and showed an almost complete absence of the low-molecular-weight subform. Conclusion: This is the first report on the effect of GH treatment on FH in children with Seckel syndrome. GH may have increased FH. In addition to growth defects and reduced BMISDS, patients with Seckel syndrome are characterized by low fasting ghrelin levels, low total ADPN, and near deficiency of the low-molecular-weight ADPN subform. The possible significance of the hormonal changes requires further investigations.

Background: Obesity is the most common chronic pediatric disease in westernized societies, with minorities and children from low socioeconomic status being mostly affected. Arab-Israelis are the largest minority population in Israel. Objective: The aim of this study is to examine the prevalence of obesity and to prospectively study the effects of a health promotion, school-based intervention on nutrition and physical activity knowledge and preferences, anthropometric measures, and fitness in Arab-Israeli kindergarten children. Participants: One hundred fifty-four children completed a school year with combined dietary-behavioral-physical activity intervention and were compared with 188 controls (age 4.2–6.5 years). Results: The prevalence of overweight and obesity among Arab-Israeli kindergarten children was 28.9%. Compared with control, the intervention led to a significantly greater (control vs. intervention, respectively, p<0.05) increase in nutrition knowledge (51.2±1.5%–48.9±1.6% vs. 48.9±1.6%–85.9±1.4%) and preferences (47.4±1.5%–47.7±1.6% vs. 45.2±1.8%–87.1±1.4%), increase in physical activity knowledge (47.2±1.3%–47.0±1.7% vs. 49.2±1.7%–90.8±1.3%) and preferences (52.3±1.3%–54.2±1.8% vs. 56.2±1.4%–92.8±1.0%), and improvement in fitness (–10.2±1.6 vs. 11.6±1.4 shuttle run laps). The intervention was associated with favorable changes in height gain (5.0±0.1 vs. 6.2±0.1 cm), body mass index (BMI –0.41±0.06 vs. –0.71±0.06 kg/m 2 ) and BMI percentile (–10.0±1.3% vs. –16.2±1.2%) in the control and intervention groups, respectively. Conclusions: A kindergarten dietary-physical activity intervention applied by the kindergarten teachers led to a decrease in BMI, BMI percentile, improved nutrition and physical activity knowledge and preferences, and improved fitness. Such programs may play important role in health promotion, prevention, and treatment of childhood obesity in minority communities from early age.

Background and aims: Manual bone age (BA) rating in precocious puberty (PP) is associated with considerable rater variability. The aim was to evaluate a new method for automated Greulich and Pyle (GP) BA determination in children with PP. Methods: Seven hundred forty-one archived X-rays from 13 boys and 103 girls with PP or early puberty of various etiologies (age range at time of X-ray, 0.3–14.8 years; mean BA advancement, 2.3 years) were rated. Automatic rating (BoneXpert BA, or BXBA) was compared with the original manual GP rating (manual BA, or ManBA). X-rays where BXBA deviated from ManBA by more than 1.5 years were rerated by three raters, and the average was formed (ReferenceBA). Results: All 741 X-rays, except nine (three images had poor quality and six were from children with a chronological age younger than 1.5 years), were analyzed automatically. The mean difference of BXBA–ManBA was –0.19 years; the SD of the differences was 0.76 years (95% confidence interval 0.72–0.80). ReferenceBA was determined for 41 images. A discrepancy from ReferenceBA greater 1.5 years was found in four images against BXBA and in 10 images against ManBA. Conclusion: Automated BA is efficient and reliable in children with PP.

Background: Carpal angle measurement is one of the anthropometrical methods to evaluate the maturation of children. Objective: To discuss the relationship between bone age and carpal angle in the maturation of children of two different generations. Subjects and methods: The first group (mid-1960s group) includes 521 Taiwanese children, 196 boys and 325 girls, growing during the agricultural period (between 1966 and 1967). The second group (mid-2000s group) includes 326 children, 74 boys and 252 girls, growing during the mid-2000s. The bone age of both groups was assessed by two leading physicians, and the carpal angle was measured by two senior radiologists. The Mann-Whitney U-test was used to compare the relationship of carpal angle and bone age among eras, sexes, and chronological ages. Results: According to the same chronological age and sexes, the carpal angle of those in the mid-2000s group was larger than that of the mid-1960s group. In addition, in the same chronological age, the results also show that the mean carpal angle of girls in both generations was larger than that of boys. However, it is notable that the carpal angle of boys in the mid-2000s group is larger than that of girls in the mid-1960s group. Furthermore, by comparing the environmental condition, we suspect that the differences between carpal angles of both generation children are caused by the great changes in socioeconomic and nutrition status in Taiwan. Conclusion: The study presents a quantitative comparison of carpal angle between two generations of Taiwanese. The preliminary result indicates that the carpal angle for the mid-2000s group is larger than that for the mid-1960s groups.

Background: Recessive mutations in ABCC8/KCNJ11 of β-cell K ATP channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. Subjects: We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited K ATP channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive K ATP channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. Conclusion: The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.

The aim of this study was to evaluate whether nocturnal melatonin concentration (NMC) and urinary 6-sulphatoxymelatonin (aMT6s) excretion can predict melatonin status in patients with severe sepsis in the pediatric intensive care unit (PICU). Blood samples for the determination of NMC were obtained from each patient at 3 a.m. Urine samples for the determination of aMT6s excretion were obtained from each patient at 12 h intervals. We obtained 89 blood and 178 urine samples from 23 septic patients, and 52 blood and 104 urine samples from 13 non-septic patients. The NMC of septic patients in a state of septic shock was significantly higher than that of septic patients not in septic shock (p=0.017) and those of non-septic patients (p=0.019). In contrast, there was no significant difference for nocturnal (NaMT6s) and total aMT6s (TaMT6s) excretion between septic patients with and without septic shock and non-septic patients (p>0.05). The NMC was significantly higher in septic patients in shock with and without hepatic dysfunction (HD) than in non-septic patients (p=0.004 and p=0.024, respectively). NaMT6s and TaMT6s excretion was significantly lower in septic patients with HD than in septic patient without HD (p=0.040 and p=0.029, for NaMT6s and TaMT6s, respectively). Our results showed that an elevated NMC may not reflect an increased MT production in septic patients in septic shock. It seems that, to evaluate the melatonin status of septic PICU patients, it is necessary to collect both serum and urine samples.

We evaluated the incidence of patient/treatment factors associated with primary ovarian failure (POF) after hematopoietic stem cell transplantation (HSCT) during childhood. Fifty girls over 12 years of age (15.0±2.2) who were referred to the pediatric endocrinology clinic between March 2002 and March 2010 after HSCT at the Catholic HSCT center were enrolled in the study. In total, 36 (72%) out of 50 patients developed POF. Twenty-three patients were diagnosed and treated as chronic graft-versus-host disease. As preparative regimens for HSCT, 23 patients received total body irradiation (TBI)-based regimen, 19 received busulfan (BU)-based regimen, 4 received both BU- and TBI-based, and 4 received reduced intensity conditioning regimen. In a univariate logistic regression analysis, the BU-based regimen (p=0.028) showed a strong relationship with POF. The incidence of POF according to the route of BU administration, between orally and intravenously, were not different (p=0.435). These results emphasize the importance of monitoring these patients at regular intervals and the need to develop complementary HSCT protocols for preventing POF in children.

Background: Vitamin D and its active form are potent immuno­modulators and are known to play an important role in the glucose/insulin metabolism. Studies on type 2 diabetes mellitus (T2DM) have shown that vitamin D increases insulin efficacy; however, there are no studies that define a similar relationship in type 1 diabetes mellitus (T1DM). The aim of this study was to investigate the relation between serum vitamin D levels and the insulin requirement used in children with T1DM. Subjects and methods: A total of 100 patients with T1DM aged 4.7–19.9 years were included in the study. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D were measured. A serum 25OHD level of <10 ng/mL was accepted as vitamin D deficiency, whereas <20 ng/mL was accepted as vitamin D insufficiency. Results: We found vitamin D deficiency in 28% and vitamin D insufficiency in 43% of our patients, whereas 29% had normal serum 25OHD levels. The insulin requirement of patients with a serum 25OHD level below 10 ng/mL were significantly higher than those of patients with a serum 25OHD level above 10 ng/mL (p=0.012). This result did not change in those with diabetes duration of over 1 year. There was weak correlation between the daily insulin requirements and serum vitamin D levels (r=–0.212, p=0.032). Conclusion: We found a significantly higher insulin requirement in T1DM children with decreased serum 25OHD levels and decreased insulin sensitivity. We recommend checking the level of serum 25OHD in children with diabetes and starting treatment if it is deficient/inadequate.

Leptin receptor gene mutations are a very rare cause of severe early-onset obesity. They are also associated with lack of pubertal development and intense hyperphagia. Presented here is a case of a 6-year-old Turkmenian girl with monogenic obesity due to a congenital deficiency of the leptin receptor. She was born from a consanguineous marriage of second cousins after 40 gestational weeks following an uncomplicated pregnancy. Her birth weight was 3500 g. However, rapid weight gain was observed after 6 months. On presentation she was 130 cm tall [>97th percentile; standard deviation score (SDS): +2], with a weight of 90 kg (>97th percentile; SDS: +5.3) and a body mass index (BMI) of 53.2 kg/m 2 (SDS: +3.6). Results of genetic evaluation revealed the patient to be homo­zygous for two missense mutations in the leptın receptor gene (P316T;W646C) resulting in complete loss of leptin receptor function. Both parents were heterozygous for the same pair of missence mutations.

A 3-year-old girl with Graves’ disease developed a generalized convulsion as a result of hypoglycemia (25 mg/dL). At the time of the hypoglycemic seizure, her plasma adrenocorticotropin (ACTH) level (1460 pg/mL) was extremely high, but her serum cortisol level (28.4 μg/dL) was relatively low given the severe stress. The cortisol-releasing hormone (CRH) provocation test done after thyroid function had improved revealed normal ACTH and cortisol responses. Since there was no other cause of hypoglycemia, such as hyperinsulin­emia, long-term starvation, suddenly advanced emaciation, or prolonged fasting, it was suspected that the transient adrenal hyporesponsiveness was the main cause of hypoglycemia.

Background: Autonomously functioning thyroid nodules (AFTN) are extremely rare in children. Malignancy may be rarely found in hyperfunctioning ‘hot’ nodules in adults. However, there are limited reports of AFTNs in young children presenting as or developing malignancy in future. We report here two young children aged <6 years old at the time of diagnosis as having an AFTN, which eventually turned out to be papillary carcinoma of thyroid (PTC) on follow-up. Patient findings: A 2-month-old baby had a right-sided neck swelling since birth. On examination, the baby had clinical and biochemical features of thyrotoxicosis. On sonography, and subsequently on 99m Tc-pertechnetate thyroid scan, a hot nodule was found. Patient was treated with carbimazole for 5 years. In spite of euthyroidism achieved, the nodule continuously grew in size. Thyroid cytology was inconclusive, hence hemithyroidectomy was performed and histopathology turned out to be PTC. Another 5-year-old female child had a large right-sided AFTN on thyroid scan. She was treated with radioiodine; however, like the previous case, the nodule started growing in size. She subsequently underwent near total thyroidectomy and histology was reported as PTC. Conclusion: In the light of this report that shows that solitary hyperfunctioning nodules in very young children have high chance of malignancy, we recommend hemithyroidectomy as the treatment of choice.

We report hyperandrogenism with severe acne, hirsutism and alopecia in a set of non-obese triplet sisters presenting at an early age. Interestingly, one of the triplets had hyperthyroidism and had significantly lower androgen level as well as hirsutism compared to her sisters. Treatment of hyperthyroidism with radioiodine ablation led to significant elevation of androgen levels and worsening of hirsutism suggesting that hyperthyroidism masks the biochemical and clinical expression of hyperandrogenism in susceptible females.

Thyroid involvement with Langerhans cell histiocytosis (LCH) is very rare. We report here the case of a 15-year-old female patient with LCH affecting the thyroid gland. She was referred to the department of pediatric endocrinology for secondary amenorrhea. Prior to the diagnosis of LCH, the patient had symptoms of diabetes insipidus (DI) and amenorrhea. The mean time from symptom onset to diagnosis was 2 years. On physical examination the patient had grade 2 goiter, and ultrasound showed bilateral multiple hypoechoic nodules and thyroid heterogeneity. Biochemical analysis indicated central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) demonstrated a mass lesion involving the hypothalamus, which appeared iso- to hypo-intense on T2-weighted images and had an intense postcontrast enhancement on T1-weighted images. Nodular goiter coinciding with a hypothalamic mass suggested LCH, and an excisional biopsy was performed. Histological evaluation of the thyroid gland revealed extensive involvement by LCH, and this was confirmed by immunohistochemical analysis showing S-100 protein and CD1a positive Langerhans cells that were weakly positive for CD68. LCH should be considered in the differential diagnosis of a diffusely enlarged firm and irregular thyroid gland and posterior or anterior pituitary dysfunction.

We describe a newborn girl with right-sided extended epidermal nevus, congenital rhabdomyosarcoma of the inguinal area at birth who had developed central precocious puberty, hemihypertrophy and vitamin D3-responsive hypophosphatemic rickets at the age of 14 months. Our patient demonstrates a much broader and polymorphic spectrum of organ systems involvement in epidermal nevus syndrome at a very early age of her life.

We describe a case of precocious puberty in a girl treated with chemoradiotherapy according to the Italian Association of Pediatric Hematology and Oncology ALL 9503 protocol for acute lymphoblastic leukemia (ALL) from the age of 15 months until the age of 3 years and 4 months. The patient was treated with chemotherapy and cranial irradiation (18 Gy in 12 fractions). At 7 years of age, during topical estrogenic treatment for congenital adhesions of the labia minora, she showed bilateral breast development that evolved into precocious puberty. A magnetic resonance imaging of the brain showed an “empty sella” (ES); the etiology of the ES, and the consequent precocious puberty, being presumably iatrogenic. Children treated with cranial radiotherapy should be carefully checked for signs of precocious puberty and the exogenous administration of estrogens should be avoided, as far as possible, because these could act as a trigger factor in a population at higher risk of precocious puberty.

There is an ongoing debate regarding the relative contribution of nurture over nature in development of gender identity. Patients with partial androgen insensitivity syndrome (PAIS) have ambiguous genitalia and are known to be reared as male or female. Familial cases of PAIS sharing common hormonal defects are usually reared in the same sex. Here, we describe two siblings with PAIS, one reared as a male and the other as female. These two siblings presented at adolescence. Gender identity was concordant with the sex of rearing for both. The male sibling was distressed with gynecomastia that had disrupted his social life. The sex of rearing seems to have played a predominant role in the formation of gender identity in these two patients with PAIS.

Neonatal diabetes mellitus (NDM) is a rare condition that can be either transient or permanent. K ATP channel (Kir6.2 or SUR1) mutation, chromosome 6 abnormalities, insulin, or glucokinase gene mutations can lead to isolated NDM. Cases caused by Kir6.2 mutation usually result in permanent NDM (PNDM) rather than transient NDM (TNDM). The majority of patients with the Kir6.2 or SUR1 mutation can be successfully managed with a sulfonylurea agent, without the need for insulin. We report a preterm male with NDM having two novel missense mutations, E322A and D352H, in the KCNJ11 gene. At 2 months of age, successful transition from insulin to glibenclamide (glyburide) therapy of the patient was managed. At 5 months of age, his diabetes went in to remission.

Hypoglycemia as an umbilical artery catheter (UAC) complication is rare. We present a neonate with hyperinsulinemic hypoglycemia due to a high-positioned UAC used inadvertently for parenteral nutrition. The aim of this report is to increase physicians’ awareness of the possibility of this rare complication.

Reninoma or juxtaglomerular cell tumor (JCT) of the kidney is a rare but curable cause of severe hypertension. We report a case of reninoma in an 18-year-old woman. Interestingly, she initially presented with dilated cardiomyopathy, without any relevant history or signs of hypertension. Malignant hypertension, one of the cardinal signs of JCT, did not become apparent in the patient until several months later. Following a thorough evaluation, we detected a small mass in the left renal cortex as well as elevated plasma renin activity, which suggested the presence of a renin-producing tumor in the kidney. The patient’s blood pressure and plasma renin activity rapidly declined after a successful laparoscopic partial nephrectomy. We postulate that hyperreninemic-hyperaldosteronism followed by fluid retention caused a sudden severe increase in ventricular afterload and subsequent congestive heart failure in this patient.

Multiple pterygium syndrome (MPS or Escobar syndrome) is a rare, generally autosomal recessive disorder characterized by multiple congenital joint contractures and multiple skin webs. An 11.5-year-old girl with a working diagnosis of Turner syndrome (TS) was referred for her phenotypic features and growth retardation. Pterygium of the neck, low posterior hairline, widely spaced nipples, cubitus valgus, upslanting palpebral fissures, hypertelorism, micrognathia, low-set ears, downturning corners of the mouth, long philtrum, high-arched palate, digital and intercrural webbings, and aplasia of the labia majora were indicative of MPS (Escobar syndrome). Her mental status was normal. Facial asymmetry was present due to cervical webs. Normal karyotype, gonadal functions, and cardiac and urinary system findings helped in excluding TS. Genetic diseases associated with skin webs were revised in differential diagnosis.

Introduction: We report a case of a male infant with the association of pseudohypertriglyceridemia, hypoadrenalism (hyponatremia, hyperpotasemia, dehydration), high creatine phosphokinase level (possible Duchenne’s muscular dystrophy, DMD) and diagnosed contiguous gene deletion syndrome in Xp21. Case report: A 1-month-old male term infant was referred due to no weight gain. The examination revealed dehydration (decreased skin turgor), scrotal hyperpigmentation and hypotonia. Laboratory findings showed hyponatremia of 124 mmol/L, hyperpotasemia of 6.9 mg/dL, high creatine phosphokinase level of 7019 IU/L, and high blood triglyceride level of 1244 mg/dL. There was no deletion detected in the dystrophin gene with the study investigating selected exons, no dystrophin staining and nonspecific atrophic findings in the muscle biopsy. Further laboratory findings defined high glycerol concentrations both in blood and in urine that were compatible with a glycerol kinase deficiency (GKD). Array CGH study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, GKD and the congenital adrenal hypoplasia (gene DAX1 or NR0B1 gene: Xp21.3-21.2). The infant showed good response to mineralocorticoid therapy, hyponatremia resolved and gained weight. Conclusion: Physicians should consider contiguous gene deletion syndrome in Xp21 in the infants with myopathic compromise, increased levels of creatine phosphokinase and pseudohypertriglyceridaemia to be able to prevent and treat the metabolic complications. Furthermore, geneticists should take into account to design routine deletion studies including the promoter region in this disorder.

Kocher-Debré-Sémélaigne syndrome (KDSS) is a rare association of muscular pseudohypertrophy and hypothyroidism in children. We report an 11-year-old female child with hypothyroidism and limb muscle pseudohypertrophy with pericardial effusion. The patient presented with hypertrichosis only. She had dull facies and marked hypertrophy of both calves and cervical muscles. Pericardial effusion was confirmed on investigations. Muscle pseudohypertrophy was a striking feature, and hypothyroidism was confirmed on thyroid studies. Pericardial effusion is known in hypothyroidism but has been very rarely reported with KDSS.

No abstract available