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Abstract Background GNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele. Patients and methods We describe a girl with a complex combination of clinical signs and a new heterozygous GNAS variant. For the molecular analysis of GNAS gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples. In silico analysis was performed to predict the possible in vivo effect of the detected novel genetic variant. The activity of Gsα protein was in vitro analyzed from samples of erythrocyte membranes, recovered from heparinized blood samples. Results We found a new heterozygous missense c.166A > T—(p.Ile56Phe) GNAS variant in exon 2, inherited from the mother that determined a reduced activity of 50% of Gsα protein function. The analysis of her parents showed a 20–25% reduction in Gsα protein activity in the mother and a normal function in the father. Clinically our patient presented a multisystemic disorder characterized by hyponatremia compatible with a nephrogenic syndrome of inappropriate antidiuresis, subclinical hyperthyroidism, subclinical hypercortisolism, precocious thelarche and pubarche and congenital bone abnormalities. Conclusions This is the first time that the new variant c.166A > T (p.Ile56Phe) on exon 2 of GNAS gene, originated on maternal allele, has been described as probable cause of a multisystemic disorder. Although the mutation is associated with a reduced activity of the function of Gsα protein, this unusual phenotype on the contrary suggests a mild functional gain.

Physical activity plays a pivotal role in preventing obesity and cardiovascular risks. The six-minute walk test (6MWT) is a tool to assess functional capacity and predict cardiovascular events. The aim of this cross-sectional study was to compare the performance and haemodynamic parameters before and after a 6MWT between obese/overweight vs. normal-weight children (average age 8.7 ± 0.7 years) participating in a project involving four primary schools in South Verona (Italy). Validated questionnaires for physical activity and diet, as well as blood drops, were collected. Overweight or obese children (OW&OB; n = 100) covered a shorter 6MWT distance compared to normal-weight children (NW, n = 194). At the test's conclusion, the OW&OB group exhibited a higher Rate Pulse Product (RPP = Systolic Blood Pressure × Heart Rate) as compared to the NW. Body Mass Index, waist-to-height ratio, fat mass by electrical impedance, and trans fatty acids showed direct correlations with pre and post-test haemodynamic parameters, such as RPP, and inverse correlations with oxygen saturation. OW&OB children demonstrated lower performance in this low-intensity exercise test, along with an elevated haemodynamic response. Excess fat in childhood can be considered a risk factor for haemodynamic stress, with potential deleterious consequences later in life. Efforts should be initiated early to break this cycle. [ABSTRACT FROM AUTHOR]

Cannabis, a plant known for its recreational use, has gained global attention due to its widespread use and addiction potential. Derived from the Cannabis sativa plant, it contains a rich array of phytochemicals concentrated in resin-rich trichomes. The main cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with CB1 and CB2 receptors, influencing various physiological processes. Particularly concerning is its prevalence among adolescents, often driven by the need for social connection and anxiety alleviation. This paper provides a comprehensive overview of cannabis use, its effects, and potential health risks, especially in adolescent consumption. It covers short-term and long-term effects on different body systems and mental health and highlights the need for informed decision making and public health initiatives, particularly regarding adolescent cannabis use. [ABSTRACT FROM AUTHOR]

Background: Newborn screening for congenital adrenal hyperplasia (CAH) based on 17-hydroxyprogesterone (17-OHP) concentration in dried blood spots has been taking place in North-Eastern Italy since 2001. Since 2017, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced, for the first time in Italy, as a second-tier test. Aims: Our study aims to evaluate, on the one hand, the effectiveness of the newborn screening for CAH after 20 years of testing and, on the other, the impact that the introduction of the second-tier test had on the diagnostic accuracy of the screening program. Methods: Since 2001 dried blood spots taken from newborns have been screened with a time-resolved fluoroimmunoassay for 17-OHP determination. Over the years, the cut-off levels of 17-OHP were adjusted according to gestational age. Since 2017, a second-tier test in LC-MS/MS was introduced for samples displaying fluoroimmunoassay 17-OHP exceeding the cut-off. Results: In total, 862,521 newborns have been screened over a period of 20 years. The total incidence of 21-hydroxylase deficiency (21-OHD) was 1:25,368, moreover, a case of 11-β-hydroxylase deficiency was identified. All these diagnoses were genetically confirmed. The sensitivity and specificity of the screening program were 97% and 99.4%, respectively. The use of LC-MS/MS as a second-tier test significantly reduced the recall rate and increased the positive predictive value. Conclusions: Screening for CAH is useful in the neonatal diagnosis of a classic form of 21-OHD, allowing a precocious treatment of affected children. The introduction of an LC-MS/MS second-tier reduced the recall rate, avoiding unnecessary blood withdrawal and medical evaluations and preventing stress to families. Furthermore, it helped identify rarer forms of CAH. [ABSTRACT FROM AUTHOR]

Introduction: Tall stature is defined as length or height more than two standard deviations above the mean for age of the reference population. There are different causes of tall stature from a familial trait or a transient anticipation of growth with no major consequences to growth disorders, such as endocrine disorder and syndromic conditions like overgrowth syndromes. Case Presentation: In this study, we reported the case of a 7-year-old girl with tall stature from birth. The patient showed a generalized overgrowth, associated with extremely advanced bone age, dysmorphic features such as a broad forehead and large extremities, and a slight neurodevelopmental delay. Laboratory tests were normal, and the main hormonal disorders were ruled out. The diagnosis of overgrowth syndrome was suspected according to the clinical presentation, and the diagnosis of Weaver syndrome was confirmed by the finding of the pathogenic mutation c.2050C> Tp.(Arg684Cys) in EZH2 gene through next generation sequencing (NGS). Conclusions: Our patient showed phenotypical features related to different overgrowth syndrome characteristics. We underlined the difficulties in reaching a clinical diagnosis in presence of tall stature. The role of molecular biology, particularly genetic analysis by NGS approach, should be considered in cases of tall stature with phenotypic overlap. [ABSTRACT FROM AUTHOR]

Background: GNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele.Patients and Methods: We describe a girl with a complex combination of clinical signs and a new heterozygous GNAS variant. For the molecular analysis of GNAS gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples. In silico analysis was performed to predict the possible in vivo effect of the detected novel genetic variant. The activity of Gsα protein was in vitro analyzed from samples of erythrocyte membranes, recovered from heparinized blood samples.Results: We found a new heterozygous missense c.166A > T-(p.Ile56Phe) GNAS variant in exon 2, inherited from the mother that determined a reduced activity of 50% of Gsα protein function. The analysis of her parents showed a 20-25% reduction in Gsα protein activity in the mother and a normal function in the father. Clinically our patient presented a multisystemic disorder characterized by hyponatremia compatible with a nephrogenic syndrome of inappropriate antidiuresis, subclinical hyperthyroidism, subclinical hypercortisolism, precocious thelarche and pubarche and congenital bone abnormalities.Conclusions: This is the first time that the new variant c.166A > T (p.Ile56Phe) on exon 2 of GNAS gene, originated on maternal allele, has been described as probable cause of a multisystemic disorder. Although the mutation is associated with a reduced activity of the function of Gsα protein, this unusual phenotype on the contrary suggests a mild functional gain. [ABSTRACT FROM AUTHOR]

Objective: Age at menarche (AAM) is an important indicator of physiological development in women, and delayed AAM has been associated with chronic illnesses. We investigated predictive factors at diagnosis that influence AAM in adolescents with chronic respiratory diseases. Study design: AAM was assessed in 1207 northern Italian female aged 11-24 (1062 healthy, 98 with asthma and 47 with cystic fibrosis [CF]). AAM was defined by recall and status quo methods. We studied anthropometric data, metabolic status, diagnosis parameters, presence of irregular menses. Clinical data of subjects with chronic respiratory illness were compared with that of healthy adolescents. Results: Mean AAM for healthy adolescents was 12.49 ± 1.2 years. Mother's AAM was positively associated with that of their daughters (P < .001). BMI was negatively correlated with AAM (P < .001). 69% of healthy adolescents referred regular menses. AAM in the different groups was 12.79 ± 3.0 years for patients with asthma (P < .05 vs healthy) and 13.24 ± 1.44 years for adolescents with CF (P < .0001 vs healthy). In the asthmatic group, 57% of the patients referred regular menses, and no significant differences were found between AAM and control of the disease (ACT test). In the CF group, no correlation was found between the type of CFTR mutation or FEV1% and AAM. 53% of the patients with CF referred regular menses. Conclusions: AAM in patients with CF and asthma was significantly higher than in healthy adolescents, and menses abnormalities were observed in the last two groups. Inflammation influences the reproductive function in chronic respiratory disease. [ABSTRACT FROM AUTHOR]

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise. [ABSTRACT FROM AUTHOR]

Background: The term premature pubarche (PP) refers to the appearance of pubic hair before age 8 in girls and before age 9 in boys. Although idiopathic PP (often associated with premature adrenarche) is considered an extreme variation from the norm, it may be an initial sign of persistent hyperandrogenism. Factors contributing to PP onset and progression have not been identified to date. Aims: The objectives of this study are to describe a group of Italian children with PP, to identify potential factors for its onset, and to define its clinical and biochemical progression. Methods: We retrospectively enrolled all infants born between 2001 and 2014 with PP. Children with advanced bone age (BA) underwent functional tests to determine the cause of PP. Hormonal analysis and BA determination were performed annually during a 4-year follow-up period. Results: A total of 334 children with PP were identified: idiopathic PP (92.5%, associated with premature adrenarche in some cases); related to precocious puberty (6.6%); late-onset 21-hydroxylase deficiency (0.9%). Low birth weight was associated with premature adrenal activation. Body mass index (BMI) was the only factor that influenced the progression of BA during follow-up. Conclusions: Low birth weight is a predisposing factor for premature adrenal activation. The increase in BMI in patients with idiopathic PP during the 4-years of follow-up was responsible for BA acceleration. We recommend prevention of excessive weight gain in children with PP and strict adherence to follow-up in order to prevent serious metabolic consequences. [ABSTRACT FROM AUTHOR]

Objectives: To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify poss ible factors predictive for GH sufficiency at puberty. Design: Clinical analysis of children affected by GHD at five time point s: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase. Methods: The study population was 80 children with idiopathic GHD and t reated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retestin g with an arginine test was performed 12 weeks later. If GH peak at retesting was =8 µg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height. Results: GH therapy was discontinued in 44 children (55%), and restarte d in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic ta rget and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty w as the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment. Conclusions: GH secretion should be retested at mid-puberty. Retesting at p uberty may reduce potential side effects and minimize costs, without impairing growth potential and final height. [ABSTRACT FROM AUTHOR]

Background: Gonadotropin-releasing hormone agonists (GnRH-a) are common treatment options for central precocious puberty (CPP) in childhood. GnRH-a treatment is useful and has a good safety profile, with minimal adverse effects and no severe long-term consequences. The common side effects in children are menopause-like symptoms and local adverse events at the injection site. Case presentation: We present the case of a girl with CPP who developed arterial hypertension from treatment with GnRH-a (triptorelin). Comprehensive diagnostic studies ruled out other causes for her hypertension and its complications. After therapy was interrupted, her blood pressure remained within normal limits for age. Consequently, we hypothesize that the hypertension presented by our patient was related to triptorelin treatment. Conclusions: Although the etiology of this adverse event is not known and only some hypotheses can be made, clinicians should be aware that arterial hypertension might appear during triptorelin treatment in childhood with CPP. Therefore, they should routinely monitor the arterial blood pressure of patients under treatment. [ABSTRACT FROM AUTHOR]

Background: Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. Aim: To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. Patients and methods: We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating. Results: Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutati ons were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variabili ty within the same mutation (3 to 360 months). No clear genotype-phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magn etic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintens ity after 6 years in one case. Conclusion: adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment. [ABSTRACT FROM AUTHOR]

We report a case of Gorham-Stout disease (GSD) complicated by chylothorax and treated with a combination therapy with interferon and bisphosphonates. This treatment may be helpful in improving the usually unfavorable prognosis of GSD beginning with a chylothorax before 1 year of age, and in reducing bone lesions. Moreover, the use of bisphosphonates appears to be useful in treating pain. [ABSTRACT FROM AUTHOR]

The Y-chromosome genes are primarily involved in sex determination, stature control, spermatogenesis, and fertility. Among structural rearrangements of the Y chromosome, the isochromosome of Yp, i(Yp), appears to be the most uncommon. We describe a detailed evolution of puberty in a boy with 45,X/46,X,i(Yp). Array CGH found 2 cell lines, one with i(Yp) and the other with monosomy X. Genetic analysis of currently known genes involved in Kallmann syndrome/normosomic central hypogonadotropic hypogonadism showed no abnormality. The patient presented with a pubertal course suggestive of a delayed puberty with gynecomastia, reduced growth rate, and infertility that need testosterone treatment to induce the appearance of the secondary sex characteristics. This patient shows the potential effects of i(Yp) and emphasizes the importance of appropriate management of puberty in people with 45,X/46,X,i(Yp). Early hormone treatment, concerns regarding fertility, emotional support, and a successful transition to adult care may help improve the physical and psychosocial well-being of affected patients. [ABSTRACT FROM AUTHOR]

The aim of this school-based study was to identify the possible association between diet and physical activity, as well as the anthropometric, vascular, and gluco-lipid parameters. We administered two validated questionnaires for diet and physical activity (Food Frequency questionnaire (FFQ), Children-Physical Activity Questionnaire (PAQ-C)) to children at four primary schools in Verona South (Verona, Italy). Specific food intake, dietary pattern, and physical activity level expressed in Metabolic Equivalent of Task (MET) and PAQ-C score were inserted in multivariate linear regression models to assess the association with anthropometric, hemodynamic, and gluco-lipid measures. Out of 309 children included in the study, 300 (age: 8.6 ± 0.7 years, male: 50%; Obese (OB): 13.6%; High blood pressure (HBP): 21.6%) compiled to the FFQ. From this, two dietary patterns were identified: “healthy” and “unhealthy”. Direct associations were found between (i) “fast food” intake, Pulse Wave Velocity (PWV), and (ii) animal-derived fat and capillary cholesterol, while inverse associations were found between vegetable, fruit, and nut intake and capillary glucose. The high prevalence of OB and HBP and the significant correlations between some categories of food and metabolic and vascular parameters suggest the importance of life-style modification politics at an early age to prevent the onset of overt cardiovascular risk factors in childhood. [ABSTRACT FROM AUTHOR]

Aim: Hypoglycemia in childhood is very rare and can be caused by genetic mutations or insulin‐secreting neoplasms. Postprandial hypoglycemia has previously been associated with insulin receptor (INSR) gene mutations. We aimed to identify the cause of postprandial hypoglycemia in a 10‐year‐old boy. Subjects: We studied the symptomatic proband and his apparently asymptomatic mother and elder brother. All of them were lean. Methods: Metabolic screening of the proband included a 5‐hour oral glucose tolerance test (OGTT), angio‐magnetic resonance imaging, and 18F‐dihydroxyphenylalanine positron emission tomography/computed tomography imaging of the pancreas. INSR gene sequencing and in vitro functional studies of a novel INSR mutation were also undertaken. Results: Fasting hyperinsulinemia was detected during metabolic screening, and 5‐hour OGTT showed hypoglycemia at 240′ in the proband, his mother, and brother. Pancreatic imaging showed no evidence of neoplasia. Acanthosis nigricans with high fasting insulin levels in the proband suggested severe insulin resistance and prompted INSR gene sequencing, which revealed the novel, heterozygous p.Phe1213Leu mutation in the patient and his family members. In vitro studies showed that this mutation severely impairs insulin receptor function by abolishing tyrosine kinase activity and downstream insulin signaling. Conclusions: The identification of etiological cause of hypoglycemia in childhood may be challenging. The combination of fasting hyperinsulinemia with acanthosis nigricans in a lean subject with hypoglycemia suggests severe insulin resistance and warrants INSR gene screening. [ABSTRACT FROM AUTHOR]

Background: Neonatal screening for 21 hydroxylase deficiency is designed to detect classical form of congenital adrenal hyperplasia (CAH). It is still unclear whether newborns who result false positives at neonatal screening might later develop signs of androgen excess. The aim of this study is to verify whether a slightly elevated 17-OHP at newborn screening is a predictive factor for premature pubarche. Methods: We evaluated all infants born between 2001 and 2014 with premature pubarche. In case of increased bone age, they were submitted to functional tests to find out the cause of their symptoms. Their 17-OHP values at newborn screening for CAH were reconsidered. Results: We identified 330 patients (269 females, 61 males) with premature pubarche. All these children had a normal 17-OHP at newborn screening with the exception of a child, born preterm and not affected by CAH. Conclusions: An elevated 17-OHP at newborn screening is not a predictive factor for premature pubarche. A likely cause of increased 17-OHP level at screening is an immaturity of adrenal gland or a neonatal stress. Therefore a strict follow up of these neonates during childhood is not necessary. [ABSTRACT FROM AUTHOR]

Background: Short stature (SS) is a relatively early sign of poor health. Only in 5% of cases we can explain it through the presence of endocrinological pathologies. Therefore, if SS is present since the first months of life, it is necessary to investigate all systemic disorders with secondary effects on growth. Case presentation: We report the case of a 16-months-old male infant with severe SS apparently not associated with other clinical signs or symptoms. The patient arrived to our attention after he was hospitalized for an Echovirus enteritis, associated to moderate neutropenia (800/mm³) and hypertransaminasemia (AST 116 U/L, ALT 88 U/L) at the age of 13 months. SS was detected in that occasion. Since SS persisted even after the complete resolution of enteritis symptoms, he was taken care by our unit. Conclusions: SS appeared in the first months of life and associated with moderate neutropenia and hypertransaminasemia led us to the diagnosis of Shwachmann-Diamond syndrome. We recommend paying further attention to this condition during the differential diagnosis of children with severe SS. [ABSTRACT FROM AUTHOR]

Background: Studies have reported that women with early menarche (≤10 years) have lower lung function. Aim: To investigate lung function in women with a history of idiopathic central precocious puberty (ICPP) treated during childhood with gonadotropin-releasing hormone agonist (GnRHa). Methods: ICPP women (n = 23) were compared with healthy age-matched controls (n = 23). Subjects were clinically evaluated by means of a questionnaire, baseline and post-β2 agonist spirometry, impulse oscillometry (a measure of airway resistance), and measurement of fraction- al exhaled nitric oxide (FeNO). Results: Patients had lower lung function values than controls: forced expiratory volume in 1 s (FEV1) (median 97.90 vs. 109.45; p = 0.011), FEV1 after β2 agonist (100.80 vs. 114.10; p = 0.013), peak expiratory flow (92.90 vs. 97.95; p = 0.031), and maximum mid-expiratory flow (MMEF) (80.80 vs. 106.30; p = 0.008). FeNO was significantly lower in the patients (p < 0.001). Significant reversibility of FEV1 after β2 agonist was observed in 8.7% of the patients. FEV1/forced vital capacity and MMEF after β2 agonist [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence of congenital hypothyroidism (CH) with delayed TSH elevation among low-birth-weight (LBW) newborns in North-Eastern Italy and to verify if they need a second or third screening. Design: Analysis of clinical and biochemical data of newborns affected by CH with delayed TSH elevation identified by neonatal screening. Methods: Data of all newborns with birth weight (BW) <2500g and evidence of delayed TSH elevation at newborn screening were collected between 2011 and 2014. Confirmatory tests were based on serum TSH and FT4 levels. All their clinical signs at diagnosis were reported. Results: 57.5% of LBW newborns with delayed TSH increase at neonatal screening presented a CH with delayed TSH elevation and began a treatment with L-thyroxine. The incidence of this condition in North-Eastern Italy is therefore 1:908. The remaining infants presented a subclinical hypothyroidism (21.25%) or a complete normal serum thyroid function (21.25%). These data could be drawn only from a retesting strategy of neonatal screening. Conclusions: Our report describes the incidence of CH with delayed TSH rise in North-Eastern Italy and differentiates this clinical condition from other thyroid dysfunctions of preterm or LBW newborns. The second-screening strategy for CH in neonates with BW<2500g proved useful in detecting newborns who otherwise would not be identified at the first screening. [ABSTRACT FROM AUTHOR]

We report the case of an infant boy with polyuria and a familial history of central diabetes insipidus. Laboratory blood tests disclosed hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Plasma magnesium concentration was slightly low. Urine analysis showed hypercalciuria, hyposthenuria, and high excretion of potassium. Such findings oriented toward type III Bartter syndrome (BSIII). Direct sequencing of the CLCNKB gene revealed no disease-causing mutations. The water deprivation test was positive. Magnetic resonance imaging showed a lack of posterior pituitary hyperintensity. Finally, direct sequencing of the AVP-NPII gene showed a point mutation (c.1884G>A) in a heterozygous state, confirming an autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). This condition did not explain the patient's phenotype; thus, we investigated for Gitelman syndrome (GS). A direct sequencing of the SLC12A3 gene showed c.269A>C and c.1205C>A new mutations. In conclusion, the patient had a genetic combination of GS and adFNDI with a BSIII-like phenotype. [ABSTRACT FROM AUTHOR]

Estrogens, growth hormones and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with gonadotropin-releasing hormone analogs (GnRHa), leads to a situation of hypoestrogenism by reducing sex-steroid levels, which, theoretically, may have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density during GnRHa treatment has been shown, but GnRHa treatment in patients with central precocious puberty does not seem to impair the achievement of normal peak bone mass at adult height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better peak bone mass achievement. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prepubertal serum inhibin B levels in monorchid boys with compensatory testicular hypertrophy (CTH) and in surgically treated cryptorchid boys with normal testicular volume. Design: Prospective study. Setting: Pediatric Division, University of Verona, Italy. Patient(s): Thirty-two prepubertal boys: 11 monorchids with CTH and 21 cryptorchids. For comparison we analyzed 15 healthy boys. Main Outcome Measure(s): All patients underwent a GnRH agonist test. Inhibin B measurement was performed at basal time. Result(s): There was a significant difference in mean testicular volume between monorchid and cryptorchid or healthy children, with boys with CTH evidencing larger testicle volume. There was no significant difference in inhibin B levels between boys with CTH and cryptorchid, but the levels were significantly lower in both groups than in the control group. Boys with CTH had significantly higher serum levels of basal FSH than children with cryptorchid. The FSH peak response to GnRH agonist stimulation was significantly higher in boys with CTH than in those with cryptorchid. Conclusion(s): Monorchid infants with CTH showed low inhibin B and high FSH levels. Our finding may confirm the hypothesis that CTH is unable to prevent testicular insufficiency in adulthood. We suggest an early hormonal evaluation of boys with CTH at puberty, together with early sperm analysis. [Copyright &y& Elsevier]

Background. Childhood obesity is becoming a major health issue and contributes to increasing the risk of cardiovascular disease in adulthood. Since dysregulated metabolism of bile acids (BAs) plays a role in progression of obesity-related disorders, including steatosis and hypertension, this study aimed to investigate BAs profiles in obese children with and without steatosis and hypertension, as well as exploring the interplay between BAs profile and vascular function. Methods. BAs concentrations were quantified with liquid chromatography-tandem mass spectrometry in 69 overweight/obese children and adolescents (mean age, 11.6 ± 2.5 years; 30 females). Liver steatosis was defined with abdomen ultrasonography, whilst hypertension was defined according to the current European guidelines. Vascular function was assessed with ultrasound technique, by measuring carotid intima media thickness (cIMT) and common carotid artery distensibility (cDC). Results. Total and individual glycine-conjugated BAs concentrations were found to be significantly higher in males compared to females, as well as in pre-pubertal compared to pubertal stage (p < 0.05 for both). No difference in BAs concentration was observed between hypertensive and normotensive subjects. Total BAs and glycine conjugated BAs were significantly higher in participants with steatosis compared to those without (p = 0.004 for both). The values of total glycine-conjugate acids were positively correlated with cDC and this association remained significant in linear regression after adjusting for sex, age, pubertal stage, body mass index and aspartate aminotransferase. Conclusion. The results suggest a possible role of BAs in the pathogenesis of liver and/or vascular damage in children and adolescent. Further studies are hence needed to validate these preliminary findings. [ABSTRACT FROM AUTHOR]

In previous studies, dietary and circulating fatty acids (FA) and desaturases activity (delta-5 desaturase [D5D], delta-6 desaturase [D6D], and stearoyl-CoA desaturase [SCD-16]) involved in their metabolism were associated with metabolic and cardiovascular disorders. The aim of the study was to assess the association between different FAs and desaturases activity (estimated as product:precursor ratios) with individual cardiovascular risk factors (in particular, anthropometric measurements and blood pressure [BP]) in children. The FA profile was determined on a whole-blood drop in 243 children (age: 8.6 ± 0.72 years) participating in a school-based cross-sectional study. Docosahexaenoic acid (DHA) inversely correlated with indices of adiposity, glucose, and triglycerides. Palmitoleic acid and SCD-16 were directly associated with markers of adiposity and BP, even after adjustment for main confounders. D6D correlated directly with the waist/height ratio. Children with excess weight (>85th percentile; that is overweight plus obese ones) showed higher palmitic acid, palmitoleic acid, and higher SCD-16 activity as compared to normal-weight children. Most of the associations were confirmed in the excess-weight group. Omega-3 FAs, particularly DHA, but not omega-6 FA, showed a potentially beneficial association with metabolic parameters, whereas palmitoleic acid and SCD-16 showed a potentially harmful association with indices of adiposity and BP, especially in obese children. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in childhood (Horm Res 70:65-72, 2008; J Clin Endocr Metab 93:869-875, 2008). Fluoro- L-dihydroxy-phenylalanine (F-DOPA) positron emission tomography (PET) can detect areas of increased activity in the pancreas and may differentiate focal from diffuse CHI (J Clin Endocr Metab 93:869-875, 2008; Radiology 253:216-222, 2009). We here report the case of a girl who complained of recurrent episodes of severe hypoglycaemia despite previous partial pancreatectomy. To evaluate the need for additional surgical intervention, we performed F-DOPA PET/computed tomography (CT), which showed a focal lesion corresponding to the anatomical region of the pancreatic tail. On the other hand, abdominal magnetic resonance imaging (MRI) clearly demonstrated that the F-DOPA uptake was in a loop of bowel occupying the previous surgical bed. Our case highlights that bowel uptake can be a possible pitfall in the interpretation of F-DOPA PET/CT in children affected by CHI, suggesting that when F-DOPA PET/CT results do not fit the clinical picture, magnetic resonance imaging (MRI) may allow a more accurate correlation of the radiotracer activity with the underlying anatomical or pathological structure. [ABSTRACT FROM AUTHOR]

Obesity is often accompanied by metabolic and haemodynamic disorders such as hypertension, even during childhood. Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP450) enzymes to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), vasoactive and natriuretic metabolites that contribute to blood pressure (BP) regulation. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 polyunsaturated fatty acids may compete with AA for CYP450-dependent bioactive lipid mediator formation. We aimed at investigating the role of AA, EPA and DHA and their CYP450-dependent metabolites in BP control and vascular function in 66 overweight/obese children. Fatty acid profile moderately correlated with the corresponding CYP450-derived metabolites but their levels did not differ between children with normal BP (NBP) and high BP (HBP), except for higher EPA-derived epoxyeicosatetraenoic acids (EEQs) and their diols in HBP group, in which also the estimated CYP450-epoxygenase activity was higher. In the HBP group, EPA inversely correlated with BP, EEQs inversely correlated both with systolic BP and carotid Intima-Media Thickness (cIMT). The DHA-derived epoxydocosapentaenoic acids (EDPs) were inversely correlated with diastolic BP. Omega-3 derived epoxymetabolites appeared beneficially associated with BP and vascular structure/function only in obese children with HBP. Further investigations are needed to clarify the role of omega-3/omega-6 epoxymetabolites in children's hemodynamics. [ABSTRACT FROM AUTHOR]

The article presents case study of a 4-year-old Caucasian boy with h bilateral facial swelling; computed tomography scan revealed both rami of the mandible with bilateral expansion, cherubism was diagnosed based on factors like age, citing that cherubism should be suspected in bilateral swelling.

In this prospective study, we analyzed 30 male infants with increased neonatal 17-hydroxyprogesterone (17OH-P) (patients) and for comparison 52 age-matched healthy babies (control subjects) with the aim of investigating the hypothalamic-pituitary-testis axis in the first 6 months of life. Although T, FSH, and LH levels were not significantly different in patients and control subjects, inhibin B was higher in patients than in control subjects. Therefore we suggest a clinical follow-up of these babies during childhood and puberty to verify the evolution of their condition. [ABSTRACT FROM AUTHOR]