Band 25, Heft 9-10

No abstract available.

Interval training is a commonly used training method known to improve both aerobic and anaerobic capabilities, and is one of the popular techniques used in training young athletes engaged in both anaerobic- and aerobic-type sports. This occurs although anaerobic glycolytic capacity is less efficient in the child and becomes increasingly more effective with age. The endocrine system, by modulation of anabolic and catabolic processes, plays a major role in the physiological adaptation to exercise training. In recent years, changes in circulating components of the growth hormone-insulin-like growth factor-1 axis, a system of growth mediators that control somatic and tissue growth, have been used to quantify the effects of training. Interestingly, exercise is also associated with remarkable changes in inflammatory cytokines, and the exercise-related response of these markers can also be used to gauge exercise load. The balance between these two seemingly antagonistic systems is believed to determine the effects of exercise. This review will summarize current knowledge on the balance of anabolic hormones and inflammatory mediators following anaerobic, interval exercise and training and its implication to young athletes.

Low bone mineral density (BMD) in patients with Turner syndrome (TS) has been reported in a considerable number of previous studies. Cortical and trabecular bone have been involved. Osteoporosis can be overdiagnosed in TS patients with a short stature unless BMD measurements are adjusted for body size. Optimization of bone health in girls with TS requires a healthy active lifestyle, including adequate calcium, vitamin D, and hormonal replacement therapy, according to consensus guidelines.

Gestational diabetes mellitus (GDM) and controversy are old friends. The impact of GDM on maternal and fetal health has been increasingly recognized. Nevertheless, universal consensus on the diagnostic methods and thresholds has long been lacking. Published guidelines from major societies differ significantly from one another, with recommendations ranging from aggressive screening to no routine screening at all. As a result, real-world practice is equally varied. This article recaps the latest evidence-based recommendations for the diagnosis and classification of GDM. It reviews the current evidence base for intensive multidisciplinary treatment of GDM and provides recommendations for postpartum management to delay and/or prevent progression to type 2 diabetes.

A model based on pubertal status and age in normal healthy children that can be used to estimate the probability that a given child will enter or progress through puberty in a given period is presented. This model could also be used to estimate the proportion of children who would be expected to have changes in their pubertal status over a given period, for example, in an interventional trial of growth promoting agents.

We report here a case of acquired hypopituitarism in a female neonate with Salmonella enteritidis sepsis and cystic encephalomalacia, after prolonged dopamine administration. Severe hyponatremia was suggestive of hypopituitarism development and the later was documented by hormonal status. This is the first report of infectious hypophysitis in neonatal age. The careful monitoring of pituitary function should be recommended for septic patients exposed to prolonged use of dopamine.

Background: Current guidelines recommend an initial L-thyroxine (L-T4) dose of 10–15 μg/kg/day for the treatment of congenital hypothyroidism (CH). We analyzed our data for the treatment outcome at 1 month after we noted a frequent overtreatment even at the lower end of this dose range. Methods: A 3-year chart review of 55 patients with confirmed CH was performed. The patients were divided to three groups based on L-T4 dose: Group 1 (6–9.9 μg/kg), Group 2 (10–11.9 μg/kg), and Group 3 (12–15 μg/kg). Overtreatment was defined as T4>16 μg/dL/free T4>2.3 ng/dL±thyroid-stimulating hormone (TSH) <0.5 μIU/L and undertreatment was defined as TSH>6 μIU/L at 1 month. Results: At 1 month, 45.8%, 37.5%, and 16.6% in Group 1, 30%, 55%, and 15% in Group 2, and 0%, 75%, and 25% in Group 3 had target labs, overtreatment, and undertreatment, respectively. Conclusions: An initial L-T4 dose of 10–11.9 μg/kg for TSH>100 μIU/L and 8–10 μg/kg for TSH<100 μIU/L at diagnosis met and often exceeded the target thyroid levels at 1 month. More frequent overtreatment was seen when >12 μg/kg was given.

Background: Reports have described that, in adults, steroids suppress thyroid-stimulating hormone (TSH) and triiodothyronine (T3) and might suppress thyroxine (T4). No data have been reported for thyroid hormone changes before or after administration of glucocorticoid in preterm infants. Aims: The aim of this study was to investigate short-term effects of thyroid hormones on preterm infants. Index cases: We measured TSH, free T3 (FT3), and free T4 (FT4) before and after one or two doses of glucocorticoids administered to five infants at 29–37 weeks of corrected gestational age. Results: Comparison of thyroid hormone levels before and 1 day after glucocorticoid administration showed that TSH significantly decreased by 76% (64%–87%), FT3 by 33% (10%–50%), and FT4 by 10% (3%–17%). The decline in TSH and FT3 was followed by an increase around the pretreatment level at 3–15 days after glucocorticoid administration. In two of the five infants, FT4 continued to decrease from 1 day after glucocorticoid administration. Conclusions: In preterm infants, assessing thyroid hormones after glucocorticoid therapy demands caution because very short-term administration causes marked changes.

Background: Migraine is the most frequent acute recurrent primary headache in childhood. Hypothyroidism may be an exacerbating factor for some primary headaches. The purpose of this study was to determine the frequency of subclinical hypothyroidism in children with migraine headache. Methods: In a cross-sectional analytic study, the thyroid function tests of 5- to 15-year-old migraineurs who were referred to the Pediatric Neurology Clinic of Shahid Sadoughi University of Medical Sciences from January 2010 to February 2011 in Yazd, Iran, were measured based on the second edition of the International Classification of Headache Disorders. Results: Forty-eight girls (46.2%) and 56 boys (53.8%) with mean age of 10.46±2.72 years were evaluated. Twenty-five (24%) children had hypothyroidism. The monthly frequency of headache (mean±SD, 14.75±8.9 vs. 20.12±9.49, p=0.04) and the duration of headache (mean±SD, 1.96±1.08 vs. 3.75±2.71 h, p=0.03) were more statistically significant in migraineur children with hypothyroidism, but the mean age, mean of onset age of migraine, sex distribution, and severity of headache were not statistically different in both groups. Conclusion: Based on the results of this study, subclinical hypothyroidism was as an exacerbating factor for migraine headache. Therefore, it is logical to check the thyroid function tests in migraineur children.

Objective: Methimazole (MMI) is used as a first-line antithyroid drug in children and adolescents with Graves’ disease (GD). The aim of this study was to evaluate the correlation between the initial dose of MMI and the clinical course of GD after treatment. Design: Retrospective and collaborative study. Setting: Nine facilities in Chiba prefecture, Japan. Patients: Sixty-four children and adolescents with GD were analyzed. The subjects were divided into three groups by the initial daily dose of MMI: group A, 0.4±0.1 mg/kg (mean±SD, n=11); group B, 0.7±0.2 (n=37); group C, 0.9±0.2 (n=16). Main outcome measures: The duration of time required for normalization of serum free T4 on initial treatment and the incidence of adverse effects for 1 year after the start of MMI were compared. Outcomes were compared among patients who were followed more than 3 years (group A, n=7; group B, n=24; group C, n=12). Results: Mean duration of times for normalization of T4 was 1.9±1.5 months in group A, 1.6±0.9 in group B and 1.9±1.5 in group C (NS). No major adverse reactions were observed. Minor adverse effects occurred in 9.1% of cases in group A, 13.5% in group B and 62.0% in group C (p<0.01). Remission rates did not differ among the three groups. Conclusions: Higher doses of MMI are harmful for initial use in children and adolescents with GD.

Polyuria is an uncommon clinical presentation in paediatric practice. When diabetes mellitus has been excluded by history taking and preliminary investigations and impaired renal concentrating ability is confirmed, water deprivation test (WDT) is necessary to differentiate among central diabetes insipidus (CDI), nephrogenic diabetes insipidus, or primary polydipsia. Traditionally, responsiveness to desmopressin injection is defined as urine osmolality >750 mOsm/kg. However, that level could not be reached in the review of our patients. We discuss how to arrive at the diagnosis of CDI in WDT. An approach to polyuria and WDT will also be discussed.

We examined the effect of training on hormonal and inflammatory response to a single volleyball practice in elite adolescent players. Fourteen male, elite, national team-level, Israeli volleyball players (age, 16.3±1.1 years, Tanner stage 4–5) participated in the study. Blood samples were collected before and immediately after a typical 60-min volleyball practice, before and after 7 weeks of training during the initial phases of the volleyball season. Hormonal measurements included the anabolic hormones growth hormone (GH), insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, and testosterone; the catabolic hormone cortisol; the pro-inflammatory markers interleukin (IL) 6, and the anti-inflammatory marker IL-1 receptor antagonist. Training led to a significant improvement of both anaerobic and aerobic properties. Before the training intervention, the typical volleyball practice was associated with a significant increase of GH and testosterone and also with a significant increase of IL-6. Training resulted in a significantly greater GH response (ΔGH, 2.5±2.4 vs. 4.7±3.0 ng/mL, before and after training, respectively; p<0.02) and reduced IL-6 response (ΔIL-6, 2.0±1.6 vs. 0.6±0.7 pg/mL, before and after training, respectively; p<0.01) to the same relative intensity volleyball practice. The results suggest that, along with the improvement of anaerobic and aerobic characteristics, training leads to a greater anabolic and reduced inflammatory response to exercise.

Zinc is an essential micronutrient for growth and development. Its deficiency causes growth retardation in children and adolescents. The present study analyzes the effect of zinc on growth hormone (GH) secretion, insulin-like growth factor 1 (IGF1), and insulin-like growth factor-binding protein 3 (IGFBP3) in normal children before puberty. Thirty normal children were studied, 15 boys and 15 girls, aged 6–9 years. They were orally supplemented with 5 mg Zn/day for 3 months and 0.06537 mg Zn/kg body weight was injected before and after oral supplementation. Dietary intake and anthropometric measurements were assessed at baseline and end of study. Plasma GH levels increased during intravenous zinc administration and IGF1 and IGFBP3 increased after oral zinc supplementation. There was a positive correlation between the areas under the curves of GH and zinc after oral supplementation. Zinc supplementation was possibly effective in improving the body zinc status of the children, secretory levels of IGF1 and IGFBP3, GH potentialization, and height.

SHOX , the short stature homeobox-containing gene, encodes a critical regulatory protein controlling long bone growth. We examined patients in one family, identified an intronic mutation, and expressed SHOX minigenes in HEK293T cells to characterize the effect on gene splicing. We identified a novel mutation at position –3 (c.-432-3C>A;g.6120C>A) of the intron 1 splice acceptor site; three short (height Z-score –2.4 to –1.7) children were heterozygous and the father (height Z-score –3.4) was homozygous. A wild-type minigene produced alternative transcripts; one utilized the normal splice site between intron 1 and exon 2, the other a cryptic splice site in exon 2. Mutant SHOX minigene generated only the smaller transcript. The exon 2 acceptor splice site is weak; an alternative transcript is normally produced using a downstream cryptic splice site. The c.-432-3C>A mutation causes further weakening, and the cryptic splice site is preferentially utilized, resulting in SHOX deficiency and short stature.

Objective: Children with growth hormone transduction defect (GHTD) have impaired growth and signal transducer and activator of transcription 3 (STAT3) activation. Here, we examine the etiology of GHTD. Methods: Control (Cf) and GHTD (Pf) children’s fibroblasts were induced with hGH, MG132, lactacystin or silence RNA/CIS (siCIS). Western immunoblotting (WI) examined protein expression. Immunofluorescent microscopy (IF) examined cellular localization. Results: (i) Pf showed retarded activation of pJAK2 and pSTAT-5 and increased ubiquitinated CIS (UbCIS) by WI. (ii) After MG132, Pf showed normal activation of pJAK2, pSTAT5 and pSTAT3. (iii) IF showed membrane (ML) and cytoplasmic localization (CL) of the GHR in Cf while the Pf showed only CL. In Pf, induction with lactacystin or siCIS changed the localization of the GHR to ML. Conclusions: In GHTD, abnormal GH signalling may be caused by over-expression of CIS, which may increase degradation of GHR, thus reducing membrane GHR availability, delaying activation of pJAK2 and pSTAT5 and reducing activation of pSTAT3.

Background: Individual responses to growth hormone (GH) treatment are variable, and efficacy should be judged in each individual patient. Objective: The aim of this study was to develop a prediction model for the growth response of GH treatment in Japanese prepubertal children with GH deficiency. Patients and methods: Pediatric patients with GH deficiency were enrolled. Auxological measurements, markers of GH status, and markers of bone metabolism were measured at baseline and at 3 and 6 months after the start of GH treatment. Correlations with height velocity (HV) at 36 months of GH treatment were calculated. Prediction models were evaluated by multiple regression analysis. Results: The model, which combined the parameters of HV at 3 months, insulin-like growth factor-binding protein 3, standard deviation score, and pyridinoline at 3 months, best predicted HV at 36 months. Conclusions: This model can accurately predict the first 3 years of growth response after 3 months of GH replacement therapy in prepubertal Japanese children.

Objective: To characterize the clinical features and biochemical status at presentation of diabetic ketoacidosis (DKA) in different age groups of children, and to analyze the outcomes of a certain treatment protocol. Methods: We reviewed records of patients with DKA who were admitted to our hospital between January 2007 and December 2010. Patients were divided into three subgroups according to age, and the results were compared between these groups. Results: One hundred thirty-four episodes in 111 patients (64 females, 47 males) were analyzed. Of these 134 episodes, 60% was in patients with new-onset diabetes and 40% was in those with established diabetes. Patients younger than 5 years had lower C-peptide and HbA1c levels than older patients at clinical onset. They were also given more alkali therapy. The initial conscious level was found closely related to plasma osmolality and serum sodium levels. Seven of 11 patients with recurrent DKA were females. No major complication was observed. Conclusion: Our study indicates that younger children are at higher risk for severe metabolic decompensation and require more attention and closer monitoring during treatment. We suggest the use of low-dose insulin in this subgroup of patients with DKA without slowing the correction of acidosis.

Background/aims: No data are available examining the relationship between carotid intima media thickness (IMT) and left ventricular mass (LVM) in obese adolescents with non-alcoholic fatty liver disease (NAFLD). Therefore, we investigated LVM and carotid IMT in obese adolescents with NAFLD. Methods: Eighty obese adolescents and 37 lean subjects were enrolled in the study. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver with high transaminases (NAFLD group and non-NAFLD group). Fasting blood samples were assayed for serum transaminases, glucose and insulin levels. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Results: LVM measurements were higher in both NAFLD and non-NAFLD obese patients in comparison with the lean children. The NAFLD group had significantly higher LVM measurements than the non-NAFLD and lean groups. Carotid IMT was higher in both the NAFLD and non-NAFLD obese patients in comparison with the lean group. The NAFLD group had significantly higher carotid IMT measurements than the non-NAFLD and lean groups. LVM was positively correlated with HOMA-IR and serum alanine aminotransferase levels in the NAFLD obese group. Carotid IMT was positively correlated with HOMA-IR, serum alanine aminotransferase levels and LVM in the NAFLD obese group. Conclusions: We demonstrated that obese adolescents with NAFLD have increased LVM and carotid IMT and low insulin sensitivity. Obese adolescents with NAFLD and increased carotid IMT may demonstrate a more adverse cardiovascular risk profile and higher LVM. Therefore, assessment of carotid IMT, in addition to echocardiography, may assist in risk stratification in obese adolescents with NAFLD with elevated cardiovascular risk factor levels.

Background: Serum ischemia modified albumin (IMA) levels have been previously studied and found to correlate with some anthropometric and laboratory measurements in adult obesity. IMA had not been studied in obese children and adolescents. Objective: The aim of the study is to analyze serum IMA levels and to evaluate their correlation with cardiovascular risk factors in obese children and adolescents with and without metabolic syndrome (MS). Subjects and methods: Sixty-one obese children/adolescents and 33 healthy children were included in the study. The obese group was divided into four subgroups, including MS (n=25), non-MS (n=36), liver steatosis (n=19) and non-liver steatosis (n=42) groups. Blood was collected to analyze biochemical parameters and IMA. Epicardial adipose tissue thickness was measured with echocardiography, and liver steotosis was determined with ultrasonography for each subject. Results: Body mass index (BMI), waist circumferences (WC), left ventricular mass (LVM) and epicardial adipose tissue (EAT) thickness were significantly higher in obese subjects. Serum IMA levels were significantly higher in the metabolic syndrome (MS) and hepatosteotosis groups. Additionally, LVM and EAT thickness were found to be correlated with serum IMA levels in these groups. Conclusions: Our study suggests that serum IMA levels may be used to predict cardiovascular risk in obese children with MS and hepatosteotosis. This may be related to the duration of obesity in childhood ending in adulthood.

Background: It is unclear to what extent insulin resistance (IR) modulates the association linking obesity to alanine aminotransferase (ALT) activity elevation. Methods: We measured the homeostatic model assessment for IR (HOMA-IR) in 1591 participants aged 12–18 years from the 2008 to 2009 Korea National Health and Nutrition Examination Survey. Results: Overweight adolescents had an odds ratio of 7.23 [95% confidence interval (95% CI), 4.33–12.10] for an elevated ALT activity compared with normal-weight adolescents, and the corresponding risk was 23.62 (95% CI, 12.98–42.98) in obese adolescents. Adjustments for other participant factors did not substantially affect the results. The addition of the HOMA-IR data decreased the estimate for overweight adolescents by 27% and for obese adolescents, the decrease was 47%. Both obesity and IR markers remained independent predictors of outcome. Conclusions: The greater the obesity level, the more that IR contributes to the association between obesity and an elevated ALT activity.

Rapid early growth is associated with adverse metabolic outcome. The aim of this study was to determine whether there are differences in body composition (BC) between very-low-birth-weight preterm (VLBWPT) infants born appropriate for gestational age (AGA) and small for gestational age (SGA) and whether these differences relate to first-year growth. Twenty-six VLBWPT (15 AGA and 11 SGA). The BC was analyzed by dual X-ray absorptiometry at 2 years, and insulin-like growth factors (IGFs) I and II and leptin were administered weekly for 8 weeks and at 1, 3, 6, and 12 months. At 24 months, the VLBW SGA infants were lighter and had less peripheral fat and lean mass than VLBW AGA infants. In all patients, the percentage of fat mass correlated inversely with the change in weight [standard deviation scores (SDS)] from newborn to 2 and 4 weeks and the 1-month leptin and lean mass (SDS) correlated inversely with the change in weight (SDS) from newborn to 2, 4, and 8 weeks and with 4-week IGF-I and 8-week IGF-II. Lean mass (SDS) inversely correlated with 6-month IGF-I and directly correlated with 1-week and 3-month IGF-I in SGA VLBW infants only. A longer follow-up period will show whether additional differences will develop later.

Gaucher disease (GD) is the most frequent autosomal recessive lysosomal glycolipid storage disorder characterized by a decreased lysosomal activity of the enzyme β-glucocerebrosidase ( GBA ; EC 3.2.1.45). The aim of this study was to evaluate the spectrum of the GBA gene mutations in Turkish GD patients and to explore genotype/phenotype associations. The molecular characterization of 32 unrelated Turkish GD patients with three types of the disease was defined. Mutation analysis identified 96.9% of the GD alleles. The N370S mutation had the highest prevalence (50%) followed by the L444P (35.5%) alleles. We identified a novel L385R missense mutation that is associated with type 1 GD.

Background: Ketotic hypoglycaemia is a common form of hypoglycaemia in childhood. Biochemically, patients present with fasting hypoglycaemia but with normal hormonal and metabolite profiles (low serum alanine levels in some patients). Glycogen Storage Disease Type 0 (GSD0) is an autosomal recessive disease due to mutations in the GYS2 gene. Patients with GSD0 also present with fasting ketotic hypoglycaemia. The frequency of GSD0 in patients presenting with ketotic hypoglycaemia is not known. Objective: To understand the frequency of GSD0 in patients presenting with ketotic hypoglycaemia and to report a novel mutation in the GYS2 gene. Subjects: The GYS2 gene was sequenced in 50 patients diagnosed with ketotic hypoglycaemia. Methods: All exons (including exon and intron boundaries) of the GYS2 gene were sequenced following amplification of the coding region by polymerase chain reaction (PCR). Results: No mutations in GYS2 were found in 49 patients. One patient had a novel homozygous mutation (c.1802T>G; p. Leu601X) in exon 14 of the GYS2 gene. We believe this is the 18th mutation reported so far. This mutation is predicted to lead to premature truncation of the glycogen synthase protein with no function. This patient presented with fasting ketotic hypoglycaemia associated with postprandial hyperglycaemia and elevated lactate level. Conclusions: GSD0 is relatively rare in patients presenting with ketotic hypoglycaemia and a normal biochemical profile. Sequencing of the GYS2 gene is more likely to be positive in patients with fasting ketotic hypoglycaemia and concomitant postprandial hyperglycaemia with hyperlactataemia.

Background: Growth hormone (GH) is critical for linear bone growth, skeletal maturation and mineralization during childhood. Aims: The aim of this study is to examine the impact of bone size and lean body mass (LBM) adjusted less head (LH) total body bone mineral content (TBBMC) in 50 prepubertal GH-deficient children. Results: The mean height (Ht) for age Z-score was –5.0±1.7. The mean total body less head (TBLH) BMC for Ht age Z-score after adjusting for TBLH LBM and TBLH BA was –3.27±0.27. The mean TBLH BMC Z-score remained below –2 even after adjustments for TBLH LBM, bone age, and Ht age, suggesting a deficit of BMC in spite of all adjustments. Applying the Molgaard approach, all children had “short bones,” 86% had “narrow bones,” and 72% had “light bones.” When adjusted for LBM, 87% of the children had low LBM for Ht and 33% had low TBLH BMC for TBLH LBM. Conclusion: LH TBBMC of children remained low, even after adjustment for bone size and LBM.

Twenty-one-hydroxylase deficient congenital adrenal hyperplasia (CAH) causes glucocorticoid and mineralocorticoid deficiency, hyperandrogenism and short stature. Management of the pubertal CAH patient is particularly challenging. The purpose of this retrospective chart review study was to determine if pubertal males and females with simple virilizing CAH (SVCAH) required different glucocorticoid dosages at progressive Tanner stages. The relationship between hydrocortisone dose and height was also assessed. Twenty females and seventeen males with SVCAH were identified and followed throughout all stages of pubertal development. Males received an average hydrocortisone dose of 16.4±4.8 mg/m 2 /day and for females, 13.7±4.6 mg/m 2 /day. The glucocorticoid dosage in males was significantly higher than in females at Tanner stages 3 through 5. Higher doses were associated with a shorter (9.6 cm) achieved than anticipated adult height.

Context: Serum anti-Müllerian hormone (AMH) is linked to the ovarian follicle pool. Little is known about the relationship between serum AMH and ovarian ultrasound (US) features in adolescents with polycystic ovary syndrome (PCOS). Objectives: To confirm that serum AMH is elevated in adolescents with PCOS and to correlate serum AMH with ovarian US features in this population are the objectives of this study. Design: A retrospective chart review of clinical, biochemical, and ultrasonographic data in adolescents with PCOS and normal controls is the design of the study. Serum AMH was measured and compared between groups and correlated with ovarian US findings. Setting: The study was done in two urban tertiary academic medical centers. Participants: Study groups included 23 adolescent females with PCOS and 12 age and BMI-matched female controls. Main outcome measures: We hypothesized that serum AMH would be elevated in the PCOS group compared with the controls and would positively correlate with the follicle number, distribution, and ovarian volume. Results: Serum AMH was 6.78±3.55 ng/mL in the PCOS group vs. 3.38±1.48 ng/mL in the controls (p=0.0004). AMH positively correlated with ovarian volume (left ovary r=0.65, p=0.0007, right ovary r=0.55, p=0.0065) and peripheral follicle distribution (p=0.0027). Ten or more follicles were observed in 83% of USs. Conclusions: There is a positive relationship between serum AMH and ovarian volume as well as peripheral follicular distribution in adolescents with PCOS. Our findings support the use of serum AMH as a useful marker to reflect ovarian US features typical of PCOS in cases where accurate USs are not available and for follow-up.

Background: Growth hormone (GH) deficiency may occur in Turner syndrome (TS), but infantile hypoglycemia attributable to TS with GH deficiency has not been reported before. Objectives: We report a puzzling case of neonatal hypoglycemia due to GH deficiency in Turner syndrome. Array CGH was used to scrutinize the complex TS karyotype. Methods: Standardized laboratory procedures. Results: In a preterm (32 weeks) with prolonged and cholestatic jaundice, recurrent hypoglycemia occurred at the age of 1.5 months and was related to GH deficiency. There were no other endocrine or syndromic features. GH therapy was started at a usual dose of 25–30 μg/kg/day, but hypoglycemia recurred. Hepatopathy and hypogammaglobulinemia suggested X-recessive GH deficiency type 3 with non-random X-inactivation but resolved spontaneously. Nonetheless, a 45,X[75]/46,X,i(Xq)[21]/47,X,i(Xq)x2[4] TS karyotype was diagnosed with an apparent isochromosome fusion at the centromere. Upon this diagnosis, GH dose was doubled (50 μg/kg/day), and blood glucose was normalized consistently. In array CGH, the signal of Xp deviated more strongly than that of Xq, but the relation of the signals differed substantially from what the karyotype predicted. The isochromosome fusion point was relocated to Xp11.22, distal to a block of mental retardation genes that escape X-inactivation. Conclusions: i) TS with GH deficiency should be considered as a potential differential diagnosis of hypoglycemia in infants requiring higher doses of GH. ii) While array CGH may be erroneous in quantification of TS mosaicism, it is useful in precisely delineating isochromosomes and identifying genes on them that escape X-inactivation and thus possibly affect the TS phenotype.

Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.

Background: The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation syndrome caused by a defect in cholesterol synthesis. Affected individuals have dysmorphism, short stature, failure to thrive, microcephaly, multiple congenital malformations, and mental retardation. Diagnostic biochemical features include low plasma cholesterol levels and elevated levels of cholesterol precursors, including 7-dehydrocholesterol (7DHC). Aims: The aim of this study is to report a case of SLOS with hypercortisolism and hypothyroidism. Settings and design: This is a case report from the genetic and metabolic unit of a tertiary care teaching hospital in north India. Methods and material: A 5-month-old male child presented with progressively increasing weight since birth. On examination, he had cyanosis, facial dysmorphism, obesity, bilateral cryptorchidism, hypospadias, inverted nipples, and systolic murmur over the left parasternal area. Investigations revealed a decreased serum cholesterol and elevated 7DHC. His serum cortisol and adrenocorticotropic hormone levels were elevated, and there was suppression of cortisol after the high-dose dexamethasone test. Magnetic resonance imaging of the brain and the pituitary region was normal. The thyroid-stimulating hormone was also elevated. Echocardiography revealed a double-outlet right ventricle with ventricular septal defect and pulmonary stenosis. Conclusions: SLOS is an inborn error of cholesterol synthesis associated with failure to thrive and malformations involving almost all the systems of the body. The occurrence of hypercortisolism, hypothyroidism, obesity, and complex cyanotic cardiac lesion in association with SLOS has not been described earlier.

Sexual development in children due to exogenous androgen exposure is rare and sparsely reported. In this paper, we present a new case of peripheral precocious puberty of exogenous origin in an 18-month-old boy due to inadvertent exposure to a testosterone gel used by his father as hormonal replacement therapy. We also review other cases in the literature. Most of these cases are due to a secondary exposure to androgen topical preparations, such as gels or creams. We highlight the value of the knowledge of the existence of these preparations to the paediatrician, given the increasingly widespread use and production of adverse effects from inadvertent contact, especially in children.

Aphallia or complete absence of penis is a rare disorder, often associated with other congenital anomalies of the genitourinary and gastrointestinal systems. This disorder is difficult to manage and has a very significant psychosocial impact on the child as well as the family. Individualized assessment and formulation of management plan is important.

Labial adhesions (synechia vulvae) are a relatively common disorder of the external genitalia in prepubertal girls. They usually occur between 3 months and 6 years of age, with a peak between 13 and 23 months of life. In the majority of cases, labial adhesions are asymptomatic and noticed by the parents or a physician during a routine physical examination. Frequently, they cause recurrent urinary tract infections. This report presents the case of a 15-month-old girl with recurrent labial adhesions and urinary tract infections. She was followed-up by a urologist from the age of 3 months, treated topically (estriol cream 1 mg/g and emollients) and surgically. No signs of androgenization were seen apart from advanced bone age. Urinary steroid profile and molecular analysis confirmed the diagnosis of non-classic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency. In the described case, a coincidence of NCCAH and labial adhesion cannot be excluded particularly in view of the resolving of urinary tract infections at the same time as resolving of labial adhesions. However, it seems that in cases of recurrent labial adhesion/synechia that require repeated surgical interventions in view of ineffectiveness of conservative treatment – as it was observed in the presented case – one should consider searching for NCCAH. This may allow not only for the causal treatment of labial adhesions but, above all, NCCAH and, in consequence, the prevention of intensification of virilization, hirsutism, menstrual cycle, and fertility disturbances that are observed starting from puberty.

A female patient with known chromosomes 18p- and 14p- presented with severe growth failure at age 2–9/12 years. Growth hormone (GH), at 0.3 mg/kg/week, was initiated at age 6–3/12 years. Her linear growth improved dramatically over the subsequent 7 years. We present details of her course and review the medical literature on the use of GH in patients with 18p-syndrome.

Thirst is stimulated by increases in effective plasma osmolality that are detected by cerebral osmoreceptors located in the vascular organ of the lamina terminalis. However, surgical destruction or organic lesions of the lamina terminalis decrease the sensation of thirst in response to increased plasma osmolality. A 17-year-old boy who was diagnosed with craniopharyngioma at the age of 10 years and underwent tumor resection and gamma knife surgery was admitted for non-symptomatic severe hypernatremia. Although the sodium level was 173 mmol/L and serum osmolality was also high (371 mOsm/kg), the patient did not report increased thirst. Laboratory analysis revealed hypertonic dehydration and acute non-oliguric renal failure due to dehydration. Treatment was based on correction of hypernatremia with hydration and education about regular, periodic water ingestion. The patient’s hypernatremia and acute non-oliguric renal failure resolved with controlled daily fluid intake. To our knowledge, this is the first report of decreased thirst sensation secondary to craniopharyngioma and tumor resection leading to severe hypernatremia and non-oliguric renal failure in an adolescent.

We describe here a Japanese male infant who transiently showed a marked elevation of midregion parathyroid hormone (M-PTH) fragments in serum with no increase in full-length 1–84 amino acid PTH and carboxy-terminal PTH fragments. He presented with a large anterior fontanel, delayed closure of the anterior fontanel, and mild short stature at 4 months old; he was normocalcemic with a normal urine calcium/creatinine ratio and absent subperiosteal bone resorption on X-ray film. Serum levels of M-PTH fragments were in >3200 pg/mL but logarithmically decreased with age. Our case report demonstrates that M-PTH fragments have no effect on calcium release from bones in humans.

Background/aims: Pseudohypoaldosteronism Type 1 (PHA1) is a rare heterogeneous syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. Multi-system form of PHA1 is caused by mutations in one of the genes encoding the α, β and γ subunits of epithelial sodium channels (ENaC). In this study, we presented a novel splice site mutation in the beta-gene of ENaC in a patient with multi-system PHA. Methods: We performed DNA sequencing analysis of SCNN1A , SCNN1B , SCNN1G and NR3C2 genes. Results: We found a novel c.1266-1G>C homozygous splice site mutation in intron 8 of the SCNN1B gene. Initially elevated plasma renin activity (PRA) and aldosterone levels of the patient returned to normal with large amounts of dietary salt and serum sodium (Na + ) and potassium (K + ) levels were within normal range at the end of the first year of life. Conclusion: This improvement may be due to partial activity of mutated ENaC subunits, reduced dependence on aldosterone in salt homeostasis with increasing age, and alternative regulating mechanisms in sodium homeostasis. The results enhance our understanding of the pathophysiology of this disorder and the mechanisms of renal salt conservation.

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