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Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. NR5A1 gene mutation is one of the principal genetic alterations implicated in causing DSD. This review outlines the role of NR5A1 gene during the process of gonadal development in humans, provides an overview of the molecular and functional characteristics of NR5A1 gene, and discusses potential clinical phenotypes and additional organ diseases due to NR5A1 mutations. NR5A1 mutations were analyzed in patients with 46,XY DSD and 46,XX DSD both during the neonatal and pubertal periods. Loss of function of the NR5A1 gene causes several different phenotypes, including some associated with disease in additional organs. Clinical phenotypes may vary, even among patients carrying the same NR5A1 variant, indicating that there is no specific genotype-phenotype correlation. Genetic tests are crucial diagnostic tools that should be used early in the diagnostic pathway, as early as the neonatal period, when gonadal dysgenesis is the main manifestation of NR5A1 mutation. NR5A1 gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty. Fertility preservation techniques should be considered as early as possible.
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Background: Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB). Methods: The main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls). Results: The three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011). Conclusions: Adolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.
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BACKGROUND AND AIM: To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional multicenter study was performed in 1469 youths (age 6-16 years) with OW/OB observed in the period 2016-2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56 > 51, Q3: ≤51 > 45, Q4: ≤45 > 41, Q5: ≤41 > 39, Q6: <39 mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33-3.16) (P < 0.01) in Q2, 1.67 (1.10-2.55) (P < 0.05) in Q3 and 1.59 (1.05-2.41) (P < 0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15-10.24) (P < 0.05) in Q2, 4.16 (1.58-10.91) (P < 0.05) in Q3 and 3.60 (1.44-9.02) (P < 0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. CONCLUSION: Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease.
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Hipertensión , Sobrepeso , Adolescente , Humanos , Niño , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Estudios Transversales , Obesidad/diagnóstico , Obesidad/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , HDL-ColesterolRESUMEN
BACKGROUND: Pseudohypoparathyroidism (PHP) is caused by loss-of-function mutations at the GNAS gene (as in the PHP type 1A; PHP1A), de novo or inherited at heterozygous state, or by epigenetic alterations at the GNAS locus (as in the PHP1B). The condition of PHP refers to a heterogeneous group of disorders that share common clinical and biological features of PTH resistance. Manifestations related to resistance to other hormones are also reported in many patients with PHP, in association with the phenotypic picture of Albright hereditary osteodystrophy characterized by short stature, round facies, subcutaneous ossifications, brachydactyly, mental retardation and, in some subtypes, obesity. The purpose of our study is to report a new mutation in the GNAS gene and to describe the significant phenotypic variability of three sisters with PHP1A bearing the same mutation. CASE PRESENTATION: We describe the cases of three sisters with PHP1A bearing the same mutation but characterized by a significantly different phenotypic picture at onset and during follow-up in terms of clinical features, auxological pattern and biochemical changes. Clinical exome sequencing revealed a never before described heterozygote mutation in the GNAS gene (NM_000516.5 c.118_139 + 51del) of autosomal dominant maternal transmission in the three siblings, confirming the diagnosis of PHP1A. CONCLUSIONS: This study reported on a novel mutation of GNAS gene and highlighted the clinical heterogeneity of PHP1A characterized by wide genotype-phenotype variability. The appropriate diagnosis has crucial implications for patient care and long-term multidisciplinary follow-up.
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Cromograninas , Subunidades alfa de la Proteína de Unión al GTP Gs , Seudohipoparatiroidismo , Humanos , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Seudohipoparatiroidismo/genética , Seudohipoparatiroidismo/diagnóstico , Cromograninas/genética , Femenino , Niño , Fenotipo , Linaje , Mutación , Adolescente , PreescolarRESUMEN
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are common autoimmune endocrine disorders in children. Studies indicate that apart from environmental factors, genetic background significantly contributes to the development of these diseases. This study aimed to assess the prevalence of selected single-nucleotide polymorphisms (SNPs) of Il7R, CD226, CAPSL, and CLEC16A genes in children with autoimmune thyroid diseases. We analyzed SNPs at the locus rs3194051, rs6897932 of IL7R, rs763361 of CD226, rs1010601 of CAPSL, and rs725613 of CLEC16A gene in 56 HT patients, 124 GD patients, and 156 healthy children. We observed significant differences in alleles IL7R (rs6897932) between HT males and the control group (C > T, p = 0.028) and between all GD patients and healthy children (C > T, p = 0.035) as well as GD females and controls (C > T, p = 0.018). Moreover, the C/T genotype was less frequent in GD patients at rs6897932 locus and in HT males at rs1010601 locus. The presence of the T allele in the IL7R (rs6897932) locus appears to have a protective effect against HT in males and GD in all children. Similarly, the presence of the T allele in the CAPSL locus (rs1010601) seems to reduce the risk of HT development in all patients.
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Enfermedades Autoinmunes , Enfermedad de Graves , Enfermedad de Hashimoto , Niño , Femenino , Masculino , Humanos , Adolescente , Prevalencia , Alelos , Enfermedad de Hashimoto/genética , Polimorfismo de Nucleótido Simple , Enfermedad de Graves/genética , Receptores de Interleucina-7/genética , Proteínas de Transporte de Monosacáridos , Lectinas Tipo C/genéticaRESUMEN
PURPOSE: ACTION Teens (NCT05013359) was conducted in 10 countries to identify perceptions, attitudes, behaviors, and barriers to effective obesity care among adolescents living with obesity (ALwO), caregivers of ALwO, and healthcare professionals (HCPs). Here, we report data from participants in Italy. METHODS: The ACTION Teens cross-sectional online survey was completed by 649 ALwO (aged 12- < 18 years), 455 caregivers, and 252 HCPs in Italy in 2021. RESULTS: Most ALwO thought their weight was above normal (69%), worried about weight affecting their future health (87%), and reported making a weight-loss attempt in the past year (60%); fewer caregivers responded similarly regarding their child (46%, 72%, and 33%, respectively). In addition, 49% of caregivers believed their child would lose excess weight with age. ALwO (38%) and caregivers (30%) most often selected wanting to be more fit/in better shape as a weight-loss motivator for ALwO; HCPs most often selected improved social life/popularity (73%). ALwO (25%) and caregivers (22%) most frequently selected lack of hunger control and not liking exercise, respectively, as weight-loss barriers, while HCPs most often agreed that unhealthy eating habits were a barrier (93%). ALwO most often obtained weight-management information from family/friends (25%) and search engines (24%); caregivers most often obtained information from doctors (29%). CONCLUSION: In Italy, the impact of obesity on ALwO was underestimated by caregivers, and ALwO and HCPs had different perceptions of key weight-loss motivators and barriers. Additionally, the internet was a key information source for ALwO, which suggests new education/communication strategies are needed. LEVEL OF EVIDENCE: IV; Evidence obtained from multiple time series with/without intervention, e.g. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05013359.
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Cuidadores , Personal de Salud , Humanos , Italia , Adolescente , Femenino , Masculino , Cuidadores/psicología , Personal de Salud/psicología , Estudios Transversales , Niño , Conocimientos, Actitudes y Práctica en Salud , Obesidad Infantil/psicología , Obesidad Infantil/terapia , Adulto , Encuestas y Cuestionarios , Obesidad/psicología , Obesidad/terapia , Conducta del Adolescente/psicologíaRESUMEN
We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.
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Enanismo Hipofisario , Hormona de Crecimiento Humana , Humanos , Niño , Hormona de Crecimiento Humana/efectos adversos , Hormona del Crecimiento/uso terapéutico , Calidad de Vida , Análisis Costo-Beneficio , Enanismo Hipofisario/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/efectos adversos , Terapia de Reemplazo de Hormonas/métodosRESUMEN
Advanced glycation end-products (AGEs) are heterogeneous compounds of irreversible adducts principally derived from nonenzymatic glycation and glycoxidation of proteins. An increase in AGEs may be involved in the pathogenesis of metabolic and cardiovascular diseases, chronic degenerative diseases, neurological diseases and cancer, and it has been suggested as a biomarker of oxidative stress. AGEs have been evaluated in different biological fluids, as well as in tissues. The most utilized techniques for AGE measurement can be divided into immunochemical methods, such as ELISA, and bioanalytical methods, including fluorescence spectroscopy, high-performance liquid chromatography, liquid chromatography-mass spectroscopy, gas chromatography-mass spectroscopy. However, the lack of reference values, well-established standard molecules, and standardized methods to measure these compounds, could limit the application of AGE evaluation for clinical purpose. Aim of this review is to provide an overview on the state of the art of the most employed techniques for detection and measurement of AGEs and their application in clinical practice.
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Enfermedades Cardiovasculares , Productos Finales de Glicación Avanzada , Biomarcadores/metabolismo , Cromatografía Líquida de Alta Presión , Productos Finales de Glicación Avanzada/análisis , Productos Finales de Glicación Avanzada/química , Productos Finales de Glicación Avanzada/metabolismo , Glicosilación , HumanosRESUMEN
Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.
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Hormona de Crecimiento Humana , Hipoglucemia , Hipopituitarismo , Recién Nacido , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/etiología , Hormona de Crecimiento Humana/uso terapéutico , Hormonas Hipofisarias , Hormona del Crecimiento/uso terapéutico , Hipoglucemia/tratamiento farmacológicoRESUMEN
AIM: To assess a new formula to improve the screening of isolated impaired glucose tolerance (IGT) in youth with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional study was performed in 1189 Caucasian youths with OW/OB aged 5-17 years, in whom impaired fasting glucose and high glycosylated hemoglobin were excluded. The sample was divided into training set (TS) (n = 883) and validation set (VS) (n = 306). Fasting (FG) and post-load plasma glucose, alanine aminotransferase (ALT), lipids and familial history for type 2 diabetes (FD) were available in all individuals. In the TS youths with IGT (n = 58, 7.0%) showed higher prevalence of female sex (FS), FD, and higher levels of FG, post-load glucose, ALT and lower levels of HDL-cholesterol vs individuals without IGT. The linear formula was obtained by logistic regression analysis in the TS: 0.05∗ALT + 0.07∗FG + 0.87∗FD + (0.06∗HDL∗ - 1) + 1∗FS. The best cut-off was 5.84. The performance of the formula vs IGT was: sensitivity: 0.74 and specificity: 0.71. Similar results were obtained in the VS. CONCLUSIONS: Using metabolic and anamnestic data we obtained a simple formula with a good performance for screening isolated IGT. This formula may support pediatricians to identify youths with OW/OB in whom the OGTT may be useful for detecting IGT.
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Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Femenino , Humanos , Adolescente , Masculino , Sobrepeso/diagnóstico , Sobrepeso/epidemiología , Intolerancia a la Glucosa/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Obesidad/diagnóstico , Obesidad/epidemiología , GlucosaRESUMEN
PURPOSE: Asprosin is a novel adipokine involved in glucose homeostasis, food intake regulation and energy homeostasis. However, the role of asprosin in glucose homeostasis regulation remains still controversial, especially in pediatrics. Aims of the study were to compare fasting serum asprosin levels between obese children and controls and to investigate the relationships of asprosin with body mass index (BMI) and biochemical markers of insulin resistance, insulin sensitivity, ß-cell function and cardio-metabolic risk in obese non-diabetic children. METHODS: This cross-sectional, case-controlled, study included 43 obese children and 24 lean matched controls consecutively recruited. Children underwent clinical and biochemical assessments, including oral glucose tolerance test. Fasting asprosin serum levels were measured using an enzyme-linked immunosorbentassay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-B), Matsuda-index, Insulinogenic-index, Areas Under the Curves for glucose and insulin were calculated. Successively, asprosin variable was dichotomized according to mean value in order to create two ordered classes of values. RESULTS: Fasting asprosin concentration was significantly lower in obese children compared to controls (331.9 ± 120.5 vs 358.1 ± 74.1 pg/ml; p = 0.013). Asprosin was lower in boys than in girls (313.7 ± 59.5 vs 361.1 ± 127.2 pg/ml; p = 0.044), while BMI standard deviation score (SDS) was higher in boys compared to girls (p = 0.024). Asprosin was negatively correlated with BMI (p = 0.024), BMI SDS (p = 0.044) and male sex (p = 0.043) in the entire cohort. No significant differences in asprosin levels were demonstrated between insulin resistant and non-insulin resistant obese children. Logistic regression models documented a significant negative association between BMI SDS and dichotomized asprosin. In particular, higher BMI SDS values were associated to lower asprosin serum levels class. A receiver operating characteristic (ROC) analysis showed existence of the best cut-off for BMI SDS (+2.7 SDS) variable into discriminating patients belonging to two asprosin classes in our cohort. CONCLUSIONS: In conclusion, asprosin serum levels were significantly lower in obese children compared to control. Fasting asprosin decreased with increasing BMI, but it was not significantly affected by IR.
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Glucemia/metabolismo , Fibrilina-1/sangre , Homeostasis , Obesidad Infantil/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Estudios de Cohortes , Femenino , Humanos , Resistencia a la Insulina , Modelos Logísticos , Masculino , Curva ROCRESUMEN
BACKGROUND: the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000-2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age. PROCEDURE: We retrospectively reconstructed an HCC course in five patients < 19 years who were identified in our departments during the period 2000-2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant. RESULTS: HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma). CONCLUSIONS: (1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.
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Adenoma Oxifílico/epidemiología , Glándula Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Adenoma Oxifílico/complicaciones , Adolescente , Niño , Femenino , Enfermedad de Hashimoto/complicaciones , Humanos , Masculino , Neurofibromatosis 1/complicaciones , Osteosarcoma/complicaciones , Estudios Retrospectivos , Pruebas de Función de la Tiroides , Neoplasias de la Tiroides/complicaciones , Adulto JovenRESUMEN
CONTEXT: The Gli-family of zinc-finger transcription factors regulates the Sonic Hedgehog (Shh) signalling pathway that plays a key role in early pituitary and ventral forebrain development. Heterozygous GLI2 loss of function mutations in humans have been reported in holoprosencephaly (HPE), HPE-like phenotypes associated with pituitary anomalies and combined pituitary hormone deficiency with or without other extra-pituitary findings. OBJECTIVE: The aim of this study was the search for GLI2 mutations in a cohort of Italian CPHD patients and the assessment of a pathogenic role for the identified variants through in vitro studies. PATIENTS: One hundred forty-five unrelated CPHD patients diagnosed with or without extra-pituitary manifestations were recruited from different Italian centres. METHODS: The GLI2 mutation screening was carried out through direct sequencing of all the 13 exons and intron-exon boundaries. Luciferase reporter assays were performed to evaluate the role of the detected missense variants. RESULTS: Five different novel heterozygous non-synonymous GLI2 variants were identified in five patients. The mutations were three missense (p.Pro386Leu, p.Tyr575His, p.Ala593Val), one frameshift (p.Val1111Glyfs*19) and one nonsense (p.Arg1226X). The latter two mutants are likely pathogenic since they lead to a truncated protein. The in vitro functional study of the plasmids bearing two of the three missense variants (namely p.Tyr575His and p.Ala593Val) revealed a significant reduction in transcriptional activity. CONCLUSION: In conclusion, the analysis of GLI2 in individuals with CPHD led to the identification of five variations with a likely negative impact on the GLI2 protein, confirming that GLI2 is an important causative gene in CPHD. The functional in vitro study analysis performed on the missense variations were useful to strengthen the hypothesis of pathogenicity.
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Hipopituitarismo/genética , Proteínas Nucleares/genética , Proteína Gli2 con Dedos de Zinc/genética , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Mutación MissenseRESUMEN
This is a retrospective multicenter nationwide Italian study collecting neonatal anthropometric data of Caucasian subjects with Prader-Willi syndrome (PWS) born from 1988 to 2018. The aim of the study is to provide percentile charts for weight and length of singletons with PWS born between 36 and 42 gestational weeks. We collected the birth weight and birth length of 252 male and 244 female singleton live born infants with both parents of Italian origin and PWS genetically confirmed. Percentile smoothed curves of birth weight and length for gestational age were built through Cole's lambda, mu, sigma method. The data were compared to normal Italian standards. Newborns with PWS showed a lower mean birth weight, by 1/2 kg, and a shorter mean birth length, by 1 cm, than healthy neonates. Females with a 15q11-13 deletion were shorter than those with maternal uniparental maternal disomy of chromosome 15 (p < .0001). The present growth curves may be useful as further traits in supporting a suspicion of PWS in a newborn. Because impaired prenatal growth increases risk of health problems later in life, having neonatal anthropometric standards could be helpful to evaluate possible correlations between the presence or absence of small gestational age and some clinical and metabolic aspects of PWS.
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Antropometría , Síndrome de Prader-Willi/patología , Peso al Nacer , Estatura , Femenino , Edad Gestacional , Humanos , Recién Nacido , Modelos Lineales , MasculinoRESUMEN
BACKGROUND: Immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia. Pediatric ITP patients are prone to develop autoantibodies such as antithyroglobulin (TG) and antithyroperoxidase (TPO), even in the absence of clinical signs of autoimmune disease. The aim of this multicenter retrospective study was to evaluate (1) the prevalence of positivity of antithyroid antibodies (TPO and TG) in a large cohort of pediatric patients with chronic ITP; (2) the role of autoimmune thyroiditis as a prognostic factor for chronicity of ITP. PROCEDURE: For this retrospective study, we collected data from patients diagnosed as affected by chronic ITP between 2011 and 2014 in six centers belonging to the Italian Association of Pediatric Haematology and Oncology (AIEOP). RESULTS: From the analysis of data, we found a significantly higher prevalence of antithyroid antibodies in children with chronic ITP (11.6%) than in the pediatric population (1.2%-1.3%). No correlation has been found between the platelet count and the prevalence of positive antithyroid antibodies at any detection time of the study. CONCLUSIONS: The results of our study demonstrated that (1) the prevalence of positivity for antithyroid antibodies (anti-TPO and anti-TG) in pediatric patients with chronic ITP results is significantly higher than in the pediatric population; (2) autoimmune thyroiditis does not seem to play a role as a prognostic factor for chronicity of ITP in pediatric patients.
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Autoanticuerpos/sangre , Biomarcadores/sangre , Yoduro Peroxidasa/inmunología , Púrpura Trombocitopénica Idiopática/sangre , Tiroiditis Autoinmune/fisiopatología , Adolescente , Autoanticuerpos/inmunología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Italia/epidemiología , Masculino , Prevalencia , Pronóstico , Púrpura Trombocitopénica Idiopática/epidemiología , Púrpura Trombocitopénica Idiopática/inmunología , Estudios Retrospectivos , Tiroiditis Autoinmune/inmunologíaRESUMEN
In a short girl with celiac disease and Hashimoto's thyroiditis (HT), suspicion of an associated pituitary lesion was suggested by the finding of a thyroid function pattern that was not compatible with HT-related hypothyroidism (low FT4 with normal TSH). This case report reinforces the view that the finding of a normal TSH in presence of a low FT4 should always alert pediatricians and raise suspicion of central hypothyroidism, even when a primary thyroid disease has been already identified. In this case TSH deficiency played a critical role in disclosing diagnosis of craniopharyngioma (CP). Therefore, the subsequent work-up was directed towards investigating pituitary function and morphology. Endocrinological investigations evidenced a picture of TSH and other pituitary hormone deficiency, whereas magnetic resonance imaging revealed an intrasellar CP. Therefore, in this case TSH deficiency played a key-role in disclosing CP diagnosis.
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Craneofaringioma/diagnóstico por imagen , Enfermedad de Hashimoto/diagnóstico , Neoplasias Hipofisarias/diagnóstico por imagen , Tirotropina/deficiencia , Estatura , Enfermedad Celíaca/complicaciones , Niño , Craneofaringioma/patología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Neoplasias Hipofisarias/patologíaRESUMEN
Introduction: Zonulin recently emerged as a valuable biological marker to assess the integrity of the intestinal mucosal barrier. Nevertheless, data about zonulin in pediatric age are extremely scarce. Aim of this study was to investigate the relationship between serum zonulin levels, both fasting and postprandial, with body mass index (BMI) and biochemical markers of insulin resistance (IR), insulin sensitivity, b-cell function and cardio-metabolic risk in obese non-diabetic youths. Methods: One hundred and four children and adolescents with obesity (BMI ≥ 2.0 SDS) were enrolled (mean age 11.43 ± 2.66). All the patients underwent clinical and biochemical assessment, including oral glucose tolerance test (OGTT) and liver ultrasonography. Zonulin serum levels were measured at fasting state, at 60-minute and 120-minute OGTT timepoint. Results: Impaired fasting glycaemia and impaired glucose tolerance were documented in 27.9% and 11.5% of patients, respectively. IR was documented in 69.2% of cases. Liver steatosis was diagnosed in 39.4%. Zonulin serum levels significantly increased from baseline to 60-minute and 120-minute OGTT timepoint (p positive correlation between BMI SDS and serum zonulin levels at 120-minute OGTT timepoint (p highlighted a positive association of zonulin fasting levels with IR and glutamicoxalacetic transaminase levels (GOT, p zonulin levels were demonstrated for age, sex, pubertal status, glucose, lipid profile and the other obesity-related parameters. Discussion: Our results show, for the first time in a pediatric cohort, the meal-related pattern of secretion of serum zonulin, which tends to significantly increase during and at 2-hours postprandial assessment. Even if the underlying mechanisms associating intestinal permeability and obesity have not been fully elucidated yet, our data confirm a close relationship between zonulin concentration and obesity in pediatric population. IR seems to significantly influence zonulin serum levels, thus a central role of IR in this pathway is conceivable.
Asunto(s)
Haptoglobinas , Resistencia a la Insulina , Obesidad Infantil , Humanos , Niño , Adolescente , Obesidad Infantil/complicaciones , Precursores de Proteínas , Resistencia a la Insulina/fisiología , AyunoRESUMEN
PURPOSE: To identify cut-off for basal LH levels and for pelvic ultrasound uterine and ovarian parameters indicating an Hypotalamic-Pituitary-Gonadal (HPG) axis activation as diagnostic of Central Precocious Puberty (CPP). METHODS: 248 girls referred for suspected precocious/early puberty who had undergone a GnRH stimulation test were enrolled and divided into three groups: Premature Idiopathic Thelarche (PIT), CPP, and Early Puberty (EA). For every patient basal serum Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH), basal LH/FSH ratio and pelvic ultrasonographic parameters were also collected. Through the use of Receiver Operating Curves (ROCs) the sensitivity (Se) and specificity (Sp) of basal LH, FSH, LH/FSH ratio and ultrasonographic parameters were evaluated at each level and Area Under the Curve (AUC) was measured. RESULTS: Basal LH model ≥0.14 mIU/mL reached the highest predictability (90.6% and 78.2%, Se and Sp, respectively). Basal LH/FSH ratio ≥0.1 showed a sensitivity of 85.90% and a specificity of 78.14%, while basal FSH cut-off (≥2.36 mIU/mL) had the lowest predictability, with a less favourable sensitivity (71%) and specificity (70.5%). Cut-off point for uterine length as 35 mm, (83.5% and 42.9% of Se and Sp, respectively) was calculated. For ovarian volumes, ROC curves showed very low sensitivity and specificity. CONCLUSION: A single basal LH measurement under the cut-off limit may be adequate to exclude an HPG axis activation as CPP.
Asunto(s)
Hormona Folículo Estimulante , Hormona Luteinizante , Pubertad Precoz , Humanos , Pubertad Precoz/sangre , Pubertad Precoz/diagnóstico , Femenino , Hormona Luteinizante/sangre , Niño , Hormona Folículo Estimulante/sangre , Sensibilidad y Especificidad , Ultrasonografía , Ovario/diagnóstico por imagen , Útero/diagnóstico por imagen , Preescolar , Tamizaje Masivo/métodos , Curva ROCRESUMEN
Childhood obesity is rapidly increasing worldwide and there is an urgent need to implement treatment and prevention programs. Over the last decade, in addition to increasing rates of childhood obesity, we have also observed rapid technological and digital development. The Covid-19 pandemic has largely contributed to both expansions but has also allowed an opening towards a broader vision of medicine, through new therapeutic opportunities such as mobile healthcare. The digital and technological delivery of obesity prevention and treatment programs can represent an innovative tool to support children and families to overcome some limitations and barriers such as the accessibility of programs that prevent them from adopting healthy lifestyle changes. This review aimed to summarize the impact of different digital interventions for children and adolescent affected by obesity.
RESUMEN
Critical illness-related corticosteroid insufficiency or CIRCI is characterized by acute and life-threatening disfunction of hypothalamic-pituitary-adrenal (HPA) axis observed among intensive care unit- staying patients.It is associated with increased circulating levels of biological markers of inflammation and coagulation, morbidity, length of ICU stay, and mortality.Several mechanisms are involved in CIRCI pathogenesis: reduced CRH-stimulated ACTH release, peripheral resistance to glucocorticoids, altered cortisol synthesis, impaired cortisol-free fraction and bioavailability.Diagnostic and therapeutic management of this condition in children is still debated, probably because of the lack of agreement among intensive care specialists and endocrinologists regarding diagnostic criteria and prevalence of CIRCI in paediatric age.In the present narrative review, we focused on definition of CIRCI in paediatric age and we advise on how to diagnose and treat this poorly understood condition, based on current literature data.