McCune-Albright Syndrome (MAS; OMIM # 174800) is a rare, sporadic disease caused by a post-zygotic, activating mutation in the guanine-nucleotide binding protein α-subunit (GNAS1) gene. MAS is characterized by the clinical triad of polyostotic fibrous dysplasia of bone, café-au-lait skin pigmentation and peripheral precocious puberty. However, clinical presentation is highly variable depending on mosaic tissue distribution of mutant-bearing cells. Precocious puberty is the most common endocrine manifestation of MAS and is often the presenting, and sometimes the only, clinical sign of MAS. Due to the very low prevalence of MAS, data on course of precocious puberty, effectiveness of treatments and gonadal function during post-pubertal period are lacking. Our knowledge on this issue derives essentially from case reports and small cohorts of patients. The aim of this review is to report all available literature data on clinical aspects, therapeutic management and outcomes of precocious puberty in children with MAS. A systematic research was carried out through MEDLINE via PubMed, EMBASE, Web of Science, Semantic Scholar, Cochrane Library.

Autoimmune thyroid diseases (AITDs), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), are the most common cause of acquired thyroid disorder during childhood and adolescence. Our purpose was to assess the main features of AITDs when they occur in association with genetic syndromes. We conducted a systematic review of the literature, covering the last 20 years, through MEDLINE via PubMed and EMBASE databases, in order to identify studies focused on the relation between AITDs and genetic syndromes in children and adolescents. From the 1654 references initially identified, 90 articles were selected for our final evaluation. Turner syndrome, Down syndrome, Klinefelter syndrome, neurofibromatosis type 1, Noonan syndrome, 22q11.2 deletion syndrome, Prader–Willi syndrome, Williams syndrome and 18q deletion syndrome were evaluated. Our analysis confirmed that AITDs show peculiar phenotypic patterns when they occur in association with some genetic disorders, especially chromosomopathies. To improve clinical practice and healthcare in children and adolescents with genetic syndromes, an accurate screening and monitoring of thyroid function and autoimmunity should be performed. Furthermore, maintaining adequate thyroid hormone levels is important to avoid aggravating growth and cognitive deficits that are not infrequently present in the syndromes analyzed.

Objective: Metabolic syndrome is a cluster of cardio-metabolic risk factors associated with an increased risk of cardiovascular disease and type 2 diabetes. In the last two decades, several definitions of metabolic syndrome have been proposed for the pediatric population; all of them agree on the defining components but differ in the suggested criteria for diagnosis. This review aims to analyze the current diagnostic criteria of metabolic syndrome in pediatrics with a reference to their feasibility and reliability in clinical practice. Methods: The systemic research was conducted from January 2003 to June 2020 through MEDLINE via PubMed, Cochrane Library and EMBASE databases. Results: After the selection phase, a total of 15 studies (182 screened) met the inclusion and exclusion criteria and hence they were reported in the present review. Twelve studies were cross-sectional, 2 were longitudinal and 1 was a consensus report. The sample population consisted of multiethnic group or single ethnic group including Turkish, European, Asian and Hispanic subjects. Conclusions: To date, there is not a univocal, internationally accepted pediatric definition of metabolic syndrome, which guarantees a high sensitivity and stability of the diagnosis. The definition proposed by IDF results the most straightforward and easy to use in clinical practice, having the unquestionable advantage of requiring measurements quickly accessible in clinical practice, without the adoption of multiple reference tables. Further research is needed to validate a new version of such definition which includes the diagnostic cut-off points recently suggested by published guidelines.

Background: Advanced glycation end-products (AGEs) and their cell receptor (RAGE) are involved in the pathophysiology of cardio-metabolic diseases. Interaction of AGEs with RAGE results in increased generation of oxygen radicals and pro-inflammatory cytokines. Circulating soluble RAGE (sRAGE) interacts with AGEs in order to counterbalance the negative effects of AGEs-RAGE interaction. Objectives: To define factors influencing AGEs, sRAGE, AGEs/sRAGE-ratio, and advanced oxidation-protein products (AOPPs) levels and to investigate changes in oxidative balance among overweight/obese children. Materials and methods: Cross-sectional, one Center, case-control study included 41 overweight and obese children aged between 5 and 16 years and 36 lean matched controls. Inclusion criteria were: BMI ≥ 1 SD; term birth; no genetic or endocrine causes of obesity; no associated chronic diseases neither chronic therapies. All patients underwent clinical and biochemical investigations (lipid and glucose profiles, liver, renal and thyroid function tests, uric acid, C-reactive protein (CRP), AGEs, sRAGE, and AOPPs serum concentrations). Significance was established at 0.050. Results: AOPPs, AGEs/sRAGE-ratio, HOMA-IR, triglycerides, triglycerides/HDL-ratio, total cholesterol (TC)/HDL-ratio, atherogenic-index of plasma (AIP), uric acid, CRP were significantly higher, whereas sRAGE and HDL were significantly lower in overweight/obese children than controls. sRAGE was significantly negatively correlated with BMI SD, TC/HDL-ratio, CRP, AOPPs, and positively with HDL. AGE/sRAGE-ratio and AOPPs were significantly positively correlated with BMI SD, TC/HDL-ratio, AIP, CRP, and negatively with HDL. BMI SD was independently associated with AGEs/sRAGE-ratio ( B = 0.06; p = 0.008), AOPPs ( B = 0.13; p = 0.02), and sRAGE ( B = −73.18; p = 0.000). Conclusions: We demonstrated, for the first time in a pediatric cohort, a significant higher value of AGEs/sRAGE-ratio among overweight/obese children, expression of a relative shift to oxidant from anti-oxidant factors, suggesting an AGE/RAGE-related oxidative homeostasis dysregulation that could enhance susceptibility to oxidative/inflammatory tissues damage. Severity of overweight, influencing the increase of oxidative stress in human organism and even in children, may contribute to the pathogenesis of long-term cardiovascular and metabolic alterations.

Background: Childhood obesity is related to a wide spectrum of cardiovascular and metabolic comorbidities.Objectives: (1) To identify precocious, preclinical, cardiovascular sonographic modifications, in a cohort of overweight (OW) and obese (OB) children and adolescents compared to lean controls; (2) to investigate the association between clinical and metabolic variables and cardiovascular sonographic parameters; (3) to evaluate their relation with two different phenotypes of obesity: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). Materials and Methods:Fifty-nine OW and OB children and adolescents (9.8 ± 2.9 years) and 20 matched lean controls underwent anthropometric, biochemical, echocardiography assessment, and sonographic evaluation of carotid artery and ascending aorta (AA). OW and OB subjects were divided in MHO and MUO, according to the Camhi et al. definition.Results: OW and OB children showed significantly higher left ventricular (LV) dimensions and mass, carotid artery intima-media thickness (CIMT), carotid stiffness [β-index, pulse wave velocity (PWV)], significantly lower mitral peak early (E) and late (A) velocity ratio (E/A ratio), and significantly impaired global longitudinal strain (GLS) compared to controls. BMI SD and HOMA-IR were positively significantly related to LV dimensions, LA volume and epicardial adipose tissue (EAT), and negative to E/A ratio. Waist circumference (WC) was positively correlated to LV dimensions, LA volume, CIMT, PWV, AA diameter, and EAT. Furthermore, WC was a strong predictor of LV dimensions, LA volume and strain, AA stiffness and diameter; BMI SD was significantly associated with EAT, LVM index, and E/A ratio; HOMA-IR and triglycerides were significant predictors of GLS. MUO patients showed higher BMI SD (p = 0.02), WC (p = 0.001), WHtR (p = 0.001), HOMA-IR (p = 0.004), triglycerides (p = 0.01), SBP (p = 0.001), as well as LV dimensions, EAT (p = 0.03), CIMT (p = 0.01), AA diameter (p = 0.02), β-index (p = 0.03) and PWV (p = 0.002), AA stiffness (p = 0.006), and significantly impaired GLS (p = 0.042) compared to MHO.Corica et al. Cardiovascular Sonographic Markers in Childhood ObesityConclusions: Severity of overweight, abdominal obesity, insulin resistance, and MUO phenotype negatively affect cardiovascular remodeling and subclinical myocardial dysfunction in OW and OB children. MUO phenotype is likely to increase the risk of developing cardiometabolic complications since the pediatric age. Distinction between MHO and MUO phenotypes might be useful in planning a personalized follow-up approach in obese children.