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Context Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children. Objective To describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI. Patients and Methods Data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected. Results The following etiologies were reported: 85% (n = 682) congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n = 25) X-linked adrenoleukodystrophy; 3.1% (n = 25) autoimmune polyglandular syndrome type 1; 2.5% (n = 20) autoimmune adrenal insufficiency; 2% (n = 16) adrenal hypoplasia congenital; 1.2% (n = 10) non-21-OHD CAH; 1% (n = 8) rare syndromes; 0.6% (n = 5) familial glucocorticoid deficiency; 0.4% (n = 3) acquired adrenal insufficiency; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis other than 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%), and hypotension (31%). Elevated adrenocorticotropic hormone (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%), and hypoglycemia (33.7%). The median age at presentation was 6.5 ± 5.1 years (0.1-17.8 years) and the mean duration of symptoms before diagnosis was 5.6 ± 11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patient-years. Three patients died from the underlying disease. Adult height, evaluated in 70 patients, was −0.70 ± 1.20 standard deviation score. Conclusions We characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.

To verify the accuracy of different indices of glucose homeostasis in recognizing the metabolic syndrome in a group of adult patients with Prader–Willi syndrome (PWS), 102 PWS patients (53 females/49 males), age ±SD 26.9 ± 7.6 yrs, Body Mass Index (BMI) 35.7 ± 10.7, were studied. The following indices were assessed in each subject during an oral glucose tolerance test (OGTT): 1 h (>155 mg/dL) and 2 h (140–199 mg/dL) glucose levels, the oral disposition index (ODI), the insulinogenic index (IGI), the insulin resistance (HOMA‐IR) were evaluated at baseline, 1 h and 2 h. Although minor differences among indices were found, according to the ROC analysis, no index performed better in recognizing MetS. Furthermore, the diagnostic threshold levels changed over the years and therefore the age‐related thresholds were calculated. The easily calculated HOMA‐IR at baseline may be used to accurately diagnose MetS, thus avoiding more complicated procedures.

The aim of the “Smuovi La Salute” (“Shake Your Health”) project was to implement an integrated and comprehensive model to prevent and treat overweight and obesity in low socioeconomic status (SES) and minority groups living in three different districts in the north of Italy. An app and a cookbook promoting transcultural nutrition and a healthy lifestyle were developed, and no-cost physical activities were organized. Healthy lifestyle teaching was implemented in 30 primary school classrooms. Learning was assessed through pre- and post-intervention questionnaires. At the Obesity Pediatric Clinic, overweight and obese children of migrant background or low SES were trained on transcultural nutrition and invited to participate in the project. Primary school students increased their knowledge about healthy nutrition and the importance of physical activity (p-value &lt, 0.001). At the Obesity Pediatric Clinic, after 6 months, pre–post-intervention variation in their consumption of vegetables and fruit was +14% (p &lt, 0.0001) and no variation in physical activity habits occurred (p = 0.34). In this group, the BMI z-score was not significantly decreased (−0.17 ± 0.63, p= 0.15). This study demonstrates the feasibility and efficacy of telematic tools and targeted community approaches in improving students’ knowledge with regard to healthy lifestyle, particularly in schools in suburbs with a high density of migrants and SES families. Comprehensive and integrated approaches provided to the obese patients remain mostly ineffective.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity. This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2–18.5) years, height SDS 0.27 ± 1.04 (−3.49–4.35), and BMI SDS 2.94 ± 0.59 (1.60–4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L. Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p

Context: Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity. Objective: To longitudinally study insulin sensitivity [via homeostasis model assessment of insulin sensitivity (HOMA-S)], insulin secretion [insulinogenic index (IGI)], and capacity of b cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in girls with Turner syndrome (TS) undergoing GH treatment. Design and Setting: Longitudinal, retrospective, 7-year study conducted in a tertiary pediatric endocrine unit and university pediatric clinic. Patients and Methods:We studied 104 patientswith TS (mean age6standard deviation, 9.163.4 years) for a median of 7.2 years. Intervention: Every year, the children underwent an oral glucose tolerance test, which was used to calculate HOMA-S, IGI, and ODI. Results: HOMA-S, IGI, and ODI did not significantly change. Conclusion: The results are reassuring, showing no negative influence of GH treatment on insulin sensitivity and on b-cell secretory capacity in girlswith TS.

Background The physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone–insulin-like growth factor (GH–IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate. Objectives To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children. Patients and Methods Ten GHD (male/female [M/F], 6/4; age [mean ± SEM], 10.7 ± 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean ± SEM], 10.3 ± 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min. Results Peak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion. Conclusions Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action.

Obesity has been considered to have a protective effect against the risk of fractures in adults. However, a high frequency of fracture is described in obese adults with Prader-Willi syndrome. To evaluate bone geometry, density and strength in a group of adult obese patients with Prader-Willi syndrome (PWS) and to examine the modulating effect on bone of treatment with growth hormone (GH) and sex steroids. This was a cross-sectional study performed in 41 (17 males, 24 females) obese subjects with genetically confirmed PWS, aged 29.4 ± 8.6 years. Forty-six healthy subjects (22 males and 24 females) served as controls. Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone to assess bone geometry, i.e. cross-sectional area (CSA), cortical area (CA), medullary area (MA), metacarpal index (MI) and bone strength evaluated as bending breaking resistance index (BBRI). DEXA was also used to evaluate body composition and bone mineral density (total body, lumbar spine and femoral neck). PWS subjects, after adjusting for height and bone size, had a reduced CSA, CA and BBRI, while bone density was not different. GH treatment had a positive effect and sex steroids a negative effect on bone size and strength. PWS subjects showed a reduced bone size at the metacarpus leading to a reduced strength, while bone density was appropriate for size. GH treatment improves bone geometry but not bone density. Bone strength was significantly reduced in PWS patients who did not receive GH and had been treated with sex steroids.

Prematurity and low birth weight are associated with a decrease in bone mass. Aim of the study was to investigate bone geometry, strength, and quality in children born at term small for gestational age (term SGA), premature appropriate for gestational age (prem AGA), and premature SGA (prem SGA). 91 patients (46 f, 45 m), mean age 11.28 years, height SDS 0.03 ± 0.21, and BMI SDS −0.31 ± 0.19. 20 were term SGA, 22 prem SGA, and 49 prem AGA. Bone geometry was assessed on the 2nd metacarpal bone, by evaluating the outer and inner diameter, the cortical area, medullary area, metacarpal index, cross-sectional area, and bone strength. Bone quality was evaluated by ultrasound and expressed as amplitude-dependent speed of sound and bone transmission time (BTT). Term SGA, prem SGA, and prem AGA had values of bone geometry, strength, and quality significantly lower than our reference range (p

Obese children have disadvantageous bone geometry, bone of low quality, and reduced strength at non-weight-bearing skeletal sites. The aim of our study was to investigate the role of parathormone (PTH) and the Wnt/β-catenin signaling pathway and its inhibitors, sclerostin and Dickkopf-1 (DKK1), as negative modulators of fat mass on bone. This was a cross-sectional observational study performed in 44 (26 males and 18 females) obese subjects, aged 11.41 ± 2.61 years. Thirty-seven normal-weight, healthy children (22 males and 15 females) of the same chronological age served as controls for the biochemical parameters and bone markers, while the data on bone geometry were evaluated according to our normative data obtained previously in a group of 325 control children. Digitalized X-rays were evaluated at the level of the second metacarpal bone for the determination of bone geometry: total cross-sectional area (TCSA), cortical area (CA), medullary area (MA), and bone strength (bending breaking resistance index [BBRI]). Serum bone markers (intact procollagen-1N-terminal propeptide [P1NP] and serum carboxy-terminal telopeptide of collagen-1 [CTX]), sclerostin, DKK1, PTH, 25-hydroxyvitamin D and were also measured. Data for TCSA, CA, MA, and BBRI are expressed as a standard deviation score in order to normalize them for age and sex. TCSA (mean ± SD, −2.92 ± 2.71), CA (−0.60 ± 0.82), MA (−0.45 ± 1.14), and BBRI (−2.65 ± 2.31) were all significantly smaller than in controls (p

Thanks to vaccination policies, Italy has a low (

A reliable surveillance system is the key to establishing connections between the epidemiological situation and the planning, monitoring and evaluation of public health interventions. Periodic evaluation of surveillance systems is essential to verify whether they are operating efficiently. In Italy, viral hepatitis is a statutorily notifiable disease and cases are reported to the notification system of the Ministry of Health. In addition, a voluntary sentinel surveillance system, named SEIEVA, coordinated by the National Institute of Health, has been active since …

Background Most estimates of disease burden due to infectious diseases focus on the impact of acute infections and do not fully capture the effects of (long-term) sequelae. To provide evidence-based and comparable estimates, the European Centre for Disease Prevention and Control (ECDC) initiated the Burden of Communicable Diseases in Europe (BCoDE) project. Methods Disability-adjusted life-years (DALYs) were used in an incidence-based and pathogen-based approach to accommodate infectious disease characteristics. This approach involves outcome trees representing the natural history of diseases and links future sequelae to the initial infection by conditional probabilities. For calculating years of life lost (YLLs), life expectancy at birth for males and females was set to 79·9 and 82·5 years, respectively (Global Burden of Disease [GBD] 2004 study standards). For YLLs due to disability, disability weights were taken from the 2004 GBD study and from additional sets or proxies. Multiplication factors (MFs) were used to adjust for underestimation of country-specific incidences (average reported cases 2005–2007). Disease models for 32 pathogens were built in Excel, where @Risk was used to model uncertainty. No time discounting or age weighting was applied. Findings Taking the example of hepatitis B in Germany, a loss of 7745 DALYs per year (95% CI 5527–10 256) was estimated, resulting in 9·4 DALYs per 100 000 (95% CI 6·7–12·4). 2·2% (170·4) of DALYs were due to acute infections. Chronic infections resulted in a loss of 2852 DALYs per year (95% CI 2455–3275). The disease burdens due to compensated liver cirrhosis, decompensated liver cirrhosis, and hepatocellular carcinoma were estimated at 637 DALYs per year (95% CI 478–792), 2150 DALYs per year (1294–3049), and 1790 DALYs per year (464–3376), respectively, together accounting for 59% (4577) of the overall DALYs. Interpretation The BCoDE methodology quantifies the burden of short-term and long-term sequelae due to present infection. Quality of notification data and choice of appropriate MFs are crucial as these are the most sensitive inputs. Funding The BCoDE consortium has been funded by the European Centre for Disease Prevention and Control (Specific agreement No. 1 to Framework Partnership Agreement GRANT/2008/003) for the conduct of burden of infectious disease studies in Europe. The funding source had no influence on writing the manuscript or on the decision to submit the abstract for publication. The corresponding author did not get any payment for writing the abstract from a pharmaceutical industry or other agency. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Nowadays, childhood obesity is one of the biggest health emergencies in the developed countries. Obesity leads to multiple metabolic alterations which increase the risk of developing diabetes and cardiovascular diseases. Thyroid function has been often described as altered in obese children, however, it is not clear whether the altered thyroid function is the cause or the consequence of fat excess. On the other hand, thyroid structure seems also to be affected. Nevertheless, both functional and structural alterations seem to improve after weight loss and therefore no treatment is needed. Conflict of interest:None declared.