Lorenzo Iughetti

Sensitivity and specificity of body mass index and skinfold thicknesses in detecting excess adiposity in children aged 8-12 years.

Primary objective : The study aimed to evaluate the sensitivity (SN) and specificity (SP) of body mass index (BMI) and skinfold thicknesses in detecting excess adiposity in children. Research design : Cross-sectional. Materials and methods : 986 children (500 females and 486 males) aged 10 - 1 years (mean - SD; range: 8-12 years) were studied. All underwent anthropometric measurements and bioelectrical impedance analysis (BIA). Dual-energy X-ray absorptiometry (DXA) was performed in 52 children to develop a population-specific algorithm for the assessment of fat-free mass (FFM) from BIA. The algorithm was applied to the remaining 934 children to estimate their FFM. Fat mass (FM) was obtained by subtracting FFM from weight (Wt). Values of FM:Wt were transformed in Z -scores and converted into 19 percentile categories (from 5 to 95 in steps of 5). The same procedure was performed with BMI and the log-transformed sum of four skinfold thicknesses (triceps, biceps, subscapular and suprailiac; lt-4SF). Excess adiposity was defined as a level of FM:Wt greater than the internally derived 85th percentile. SN and SP of each internally derived percentile of BMI and lt-4SF in detecting excess adiposity were calculated. Results : In the pooled sample ( n = 934), SN and SP were 0.39 and 0.99 for the 95th percentile of BMI, 0.65 and 0.95 for the 85th percentile of BMI, and 0.75 and 0.94 for the 85th percentile of lt-4SF. Conclusions : BMI percentiles employed in the present study have a high SP but a low SN in detecting excess adiposity in 8-12-year-old children. The use of the sum of four skinfolds has the potential to increase the SN of a screening programme for excess adiposity in children of this age.

Obesity in patients with acute lymphoblastic leukemia in childhood

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy) or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty‐five medical centers and the Prader–Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4–46.7). Two hundred thirty‐eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity‐related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.

Diagnosis of central precocious puberty: endocrine assessment.

The new methods which are currently available have provided substantial help in performing the differential diagnosis of CPP, especially in detecting very early modifications of gonadotropin secretion. Nocturnal sampling is not a practical tool and generates discomfort for patients, and daytime samples do not yet have sufficient sensitivity; thus, determination of LH levels after GnRH stimulation is the most important test. We emphasize that the use of the GnRH agonist test improves the discrimination of the endocrine investigation, making it easier to differentiate CPP from other conditions, such as thelarche. Determination of sex steroids is necessary, but its use in isolation is not recommended.

Increased visceral adipose tissue is associated with increased circulating insulin and decreased sex hormone binding globulin levels in massively obese adolescent girls.

The current study was designed to examine the relationship between body fat distribution, as evaluated by anthropometry and magnetic resonance imaging (MRI), and circulating insulin, sex hormone and SHBG levels in obese adolescent girls. Twenty-nine obese adolescent girls, aged 12.6–16.9 years with a mean BMI of 30.51±1.86 participated in this study. All girls had breast stage B4-5 and pubic hair stage P4-5. Percent obesity and BMI as indices of being overweight were calculated; the waist-to-hip ratio (WHR) and the waist-to-thigh ratio (WTR) were calculated to obtain two anthropometric indices for the pattern of body fat distribution. The areas of visceral (VAT) and subcutaneous adipose tissue (SAT) were evaluated by MRI at the L4–L5 level. Serum concentrations of total T, DHEAS, 17β-estradiol, progesterone and SHBG were measured. Plasma glucose and insulin concentrations were evaluated during an oral glucose tolerance test. WHR was the only anthropometric parameter that was significantly associated with the area of VAT. Insulin level showed correlation with both WHR and the area of VAT; no correlation was found between insulin levels and WTR. Both WHR and VAT were negatively correlated with serum DHEAS level and positively correlated with T level. There were strong negative correlations between serum SHBG level and the area of VAT and WHR. Inverse correlation was found between serum SHBG level and insulin. Serum 17β-estradiol and progesterone levels showed no significant correlation with all the patterns of body fat distribution. SAT was not significantly correlated with both anthropometric parameters and any of the sex hormones evaluated. We can draw two main conclusions. Firstly, in massively obese adolescent girls, the WHR seems to be a good indicator for the accumulation of VAT, and abdominal obesity, rather than adiposity per se, appears to be related to biochemical complications. Secondly, increased upper body adiposity and, in particular, the intra-abdominal fat area are associated with increased insulin levels in massively obese adolescent girls. The associated reductions in SHBG and DHEAS levels represent an early general risk factor for the development of metabolic and cardiovascular diseases in this population, as previously described for obese adult women.

Plasma brain-derived neurotrophic factor concentrations in children and adolescents

BACKGROUND Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity influencing learning, memory and cognitive behavior. The aim of this study is to assess plasma BDNF variations according to pubertal status. METHODS A total of 110 subjects were included in the study. Blood samples were collected after overnight fasting. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. Gonadotrophins, sex steroids, and IGF-1 were also assessed. RESULTS BDNF was positively correlated with platelet count and negatively associated with both BMI and age. BDNF levels in pubertal males were significantly lower than prepubertal males and both prepubertal and pubertal females. CONCLUSIONS Plasma BDNF levels seem to be influenced by hormonal status. We demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF blood levels and platelets remain the most important predictor of their concentration. Further studies are necessary to better understand the role of this neurotrophin in pubertal development.

Genotype/phenotype correlations of males affected by Simpson-Golabi-Behmel syndrome with GPC3 gene mutations: patient report and review of the literature.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome with associated visceral and skeletal anomalies. Deletions or point mutations involving the glypican-3 (GPC3) gene at Xq26 are associated with a relatively milder form of this disorder (SGBS1). GPC3 encodes a putative extracellular proteoglycan, glypican-3, that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed. It appears to form a complex with insulin-like growth factor-II (IGF-II), and might thereby modulate IGF-II action. We reviewed the clinical findings of all published patients with SGBS1 with GPC3 mutations to confirm the clinical specificity for the SGBS1 phenotype. Moreover, we report on a new patient with a GPC3 deletion and IGF-II evaluation.

Gut Microbiota and Celiac Disease

Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.

Endocrine Aspects of Coeliac Disease

Coeliac disease (CD) is a permanent intolerance to gluten that results in damage of the small intestinal mucosa, and it is one of the common causes of chronic malabsorption in children. It is well known that patients with CD are at great risk of malignant complications, but in patients with CD many other disorders have been recognized. Autoimmunity diseases, such as type 1 diabetes mellitus, thyroid diseases, and autoimmune polyglandular syndromes are known to be associated with CD, and they seem to be related to gluten exposure. Growth, bone metabolism, and fertility can be affected in patients with CD, especially if they are not on a gluten-free diet. We review the literature on endocrine aspects of CD, because patients with CD are at great risk of developing endocrine disorders.

Pelvic ultrasound and color Doppler findings in different isosexual precocities

To evaluate the role of ultrasound and color Doppler analyses in improving the differential diagnosis of pubertal precocities.