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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.

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: Growth hormone (GH) influences glucose homeostasis by negatively affecting insulin sensitivity, leading to a compensatory increase in insulin secretion. It has recently been reported, in animals and humans, that GH might also stimulate insulin secretion by directly affecting the growth and function of pancreatic β-cells. The aim of this work was to longitudinally study the insulin sensitivity (HOMA-S), insulin secretion [insulinogenic index (IGI)] and capacity of β-cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in GH-deficient (GHD) children under GH treatment. Methods: We studied 99 GHD (62 male, 37 female; age 8.9 ± 3.5 years) children for a median period of 6 years (range 1.5-16.2). Every year, our patients underwent an oral glucose tolerance test, which was used to calculate the HOMA-S, IGI and ODI. Results: Although HOMA-S remained unchanged, an increase in IGI and ODI was observed, becoming significant after 6 years of treatment (1.25 ± 1.28 vs. 2.35 ± 2.38, p < 0.05 and 0.57 ± 0.68 vs. 1.50 ± 1.92, p < 0.01, respectively). Conclusion: Our results suggest a positive influence of GH treatment on the β-cell secretory capacity in children with GH deficiency.

Background Growth hormone (GH) has a strong positive influence on bone, stimulating both bone elongation and increase in size. The aim of the study was to compare the effect of two different GH dosages on final height and bone geometry in two groups of GH-deficient children. Methods We evaluated 121 children (86 m, 35f). Group 1 (77 patients) treated with GH at a mean dose of 0.16 mg/kg/week and group 2 (44 patients) at 0.3 mg/kg/week. Bone geometry was evaluated at final height from a digitalized X-ray of the left hand considering the following parameters: metacarpal index (MI), cross-sectional area (CSA), cortical area (CA) and medullary area (MA). Results At baseline, group 2 was shorter than group 1 (−1.54 vs −1.01 SDS; p

Italy is the sixth largest country in Europe and has the second highest average life expectancy, reaching 79.4 years for men and 84.5 years for women in 2011. There are marked regional differences for both men and women in most health indicators, reflecting the economic and social imbalance between the north and south of the country. The main diseases affecting the population are circulatory diseases, malignant tumours and respiratory diseases. Italy's health care system is a regionally based national health service that provides universal coverage largely free of charge at the point of delivery. The main source of financing is national and regional taxes, supplemented by copayments for pharmaceuticals and outpatient care. In 2012, total health expenditure accounted for 9.2 percent of GDP (slightly below the EU average of 9.6 percent). Public sources made up 78.2 percent of total health care spending. While the central government provides a stewardship role, setting the fundamental principles and goals of the health system and determining the core benefit package of health services available to all citizens, the regions are responsible for organizing and delivering primary, secondary and tertiary health care services as well as preventive and health promotion services. Faced with the current economic constraints of having to contain or even reduce health expenditure, the largest challenge facing the health system is to achieve budgetary goals without reducing the provision of health services to patients. This is related to the other key challenge of ensuring equity across regions, where gaps in service provision and health system performance persist. Other issues include ensuring the quality of professionals managing facilities, promoting group practice and other integrated care organizational models in primary care, and ensuring that the concentration of organizational control by regions of health-care providers does not stifle innovation.

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

SummaryObjective It is still not known whether fat mass excess could exert a positive effect on bone. The aim of our study was to evaluate bone strength and quality in a group of overweight and obese children and adolescents by assessing bone geometry at metacarpal bones and ultrasound at phalangeal level. Design and patients This is a cross sectional observational study performed in 123 subjects, aged 11·2 ± 2·9 years. Measurements Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone for the determination of the outer (D) and inner (d) diameter, cortical area (CA), medullary endocortical area (EA), metacarpal index (MI) and bone strength (Bending Breaking Resistance Index; BBRI). A total of 98 subjects underwent amplitude dependent speed of sound (Ad-SOS) and bone transmission time (BTT) assessment by phalangeal ultrasonography. Results SDs for each measured parameter were as follows: Males: D = −0·71 ± 0·95, d = −0·29 ± 0·86, CA = −0·69 ± 0·69, EA = −0·32 ± 0·79, Ad-SOS = −1·14 ± 0·91, BTT = −1·17 ± 1·11 and BBRI (417 ± 151 vs 495 ± 174 mm3) were all significantly lower than in controls (P