High prevalence of hypovitaminosis D in Sicilian children affected by growth hormone deficiency and its improvement after 12 months of replacement treatment.

PURPOSE: Although the correlation between vitamin D and growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis is documented, as of date, few and conflicting studies have prospectively analyzed vitamin D before and after GH treatment. Our aim was to evaluate as to how the condition of GH deficiency (GHD) or GH treatment influences vitamin D in children. METHODS: Eighty Sicilian GHD children (M/F 58/22; mean age 10.3 years), grouped according to the season of evaluation in group A (June-September; 41 children) and group B (November-February; 39 children), were evaluated at baseline and after 12 months of GH treatment. RESULTS: Twenty-eight children (35 %) were vitamin D insufficient and 32 (40 %) deficient at baseline, and lower vitamin D levels were found in group B than in A (17.3 ± 5.3 vs. 31.1 ± 11.1 ng/ml; p < 0.001). A positive correlation between vitamin D and baseline GH levels (p < 0.001) was found. After 12 months, increased vitamin D was found both in all children (34.4 ± 16.4 vs. 24.5 ± 11.1 ng/ml; p = 0.002) and in group A (38.5 ± 14 vs. 31.1 ± 11.1 ng/ml; p < 0.001) and B (30 ± 17.7 vs. 17.3 ± 5.3 ng/ml; p < 0.001). Overall, only 25 (31 %) children remained insufficient and 15 (19 %) deficient, with an increase in prevalence of children with normal levels (p = 0.001). CONCLUSIONS: Our data demonstrated a very high prevalence of hypovitaminosis D in Sicilian GHD children, with an improvement after 12 months of GH treatment. Vitamin D assessment should therefore be considered routinely in GHD children both at diagnosis and during the follow-u

Abitare la sanità: la riqualificazione dell'edilizia ospedaliera mediante il Building information modeling

2013 - 2014XIII n.s

Vitamin D Deficiency in Cushing's Disease: Before and After Its Supplementation

Background: The primary objective of the study was to assess serum 25-hydroxyvitamin D [25(OH)D] values in patients with Cushing's disease (CD), compared to controls. The secondary objective was to assess the response to a load of 150,000 U of cholecalciferol. Methods: In 50 patients with active CD and 48 controls, we evaluated the anthropometric and biochemical parameters, including insulin sensitivity estimation by the homeostatic model of insulin resistance, Matsuda Index and oral disposition index at baseline and in patients with CD also after 6 weeks of cholecalciferol supplementation. Results: At baseline, patients with CD showed a higher frequency of hypovitaminosis deficiency (p = 0.001) and lower serum 25(OH)D (p &lt; 0.001) than the controls. Six weeks after cholecalciferol treatment, patients with CD had increased serum calcium (p = 0.017), 25(OH)D (p &lt; 0.001), ISI-Matsuda (p = 0.035), oral disposition index (p = 0.045) and decreased serum PTH (p = 0.004) and total cholesterol (p = 0.017) values than at baseline. Multivariate analysis showed that mean urinary free cortisol (mUFC) was independently negatively correlated with serum 25(OH)D in CD. Conclusions: Serum 25(OH)D levels are lower in patients with CD compared to the controls. Vitamin D deficiency is correlated with mUFC and values of mUFC &gt; 240 nmol/24 h are associated with hypovitaminosis D. Cholecalciferol supplementation had a positive impact on insulin sensitivity and lipids

Hutchinson Gilford Progeria Syndrome: A Therapeutic Approach via Adenoviral Delivery of CRISPR/cas Genome Editing System

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare human genetic disease caused by mutations in the LMNA gene. LMNA codes for structural components of the nuclear lamina. Alterations of nuclear lamina lead to a very variable class of diseases known as laminopathies. In detail, HGPS manifests a severe premature ageing phenotype due to the accumulation of a dominant negative form of lamin-A called progerin. With current treatments, the life expectancy of HGPS patients does not exceed their second decade. Death is usually due to cardiovascular complications. Recently, a new technology for mammals in vivo gene editing has been developed: the clustered regularly interspaced short palindromic repeats/Cas protein (CRISPR/Cas) system. The CRISPR/Cas technology permits to edit the genome at specific loci. Even if the CRSIPR/Cas constructs are transiently administered to the target cells, the genome editing is permanent. The advantages of the combination of non-integrating transient vectors in combination with the CRISPR/Cas constructs could give rise to a secure approach for the treatment of disease of genetic origin, especially those caused by dominant negative mutations, such as HGPS. A potential application of non-integrating transient vectors carrying CRISPR/Cas constructs for the treatment of HGPS will be discussed in detail

Utility of C-peptide for a reliable estimate of insulin secretion in children with growth hormone deficiency.

OBJECTIVE: GH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic β-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of β-cell function than insulin, but few studies evaluated it during GHT. Our aim was to assess the usefulness of C-peptide in the evaluation of insulin secretion in GH deficiency (GHD) children. DESIGN: In 48 GHD children, at baseline and after 12 and 24months of GHT, and in 56 healthy subjects we evaluated fasting and glucagon-stimulated (AUCCpep) C-peptide levels in addition to other commonly used secretion indexes, such as fasting and oral glucose tolerance test-stimulated insulin levels (AUCINS), Homa-β, and insulinogenic index. The main outcomes were the change in C-peptide during GHT and its correlation with the auxological and hormonal parameters. RESULTS: At baseline GHD children showed a significant lower AUCCpep (p=0.006), while no difference was found for the other indexes. Both fasting C-peptide (beta 0.307, p=0.016) and AUCCpep (beta 0.379, p=0.002) were independently correlated with IGF-I SDS, while no correlation was found for all other indexes. After 12months an increase in Homa-β (p<0.001), fasting C-peptide (p=0.002) and AUCCpep (p<0.001) was found. At multivariate analysis, only fasting C-peptide (beta 0.783, p=0.001) and AUCCpep (beta 0.880, p<0.001) were independently correlated with IGF-I SDS. CONCLUSIONS: C-peptide, rather than the insulin-derived indexes, has proved to be the most useful marker of insulin secretion correlated to IGF-I levels in GHD children. Therefore, we suggest the use of glucagon test both as diagnostic test for the GH assessment and as a useful tool for the evaluation of insulin secretion during GHT in children

Comparison between euglycemic hyperinsulinemic clamp and surrogate indices of insulin sensitivity in children with growth hormone deficiency

Objective: Data about the impact of growth hormone treatment (GHT) on insulin sensitivity in children are quite controversial, due to the different surrogate indices that have been used. Design: We evaluated insulin sensitivity through the euglycemic hyperinsulinemic clamp, considered the gold standard technique, in 23 children affected by growth hormone deficiency (GHD) at baseline and after 12. months of GHT and in 12 controls with short stature at baseline, and we compared the clamp-derived index (M-value) with the most commonly used surrogate index of insulin sensitivity, as ISI Matsuda, and with circulating plasma markers of insulin sensitivity, as adiponectin and resistin levels. Results: At baseline, no significant difference in all metabolic parameters between GHD children and control subjects was found. After 12. months of GHT, GHD children showed a significant increase in fasting insulin (p <. 0.001) and resistin (p = 0.028) and a decrease in ISI Matsuda (p <. 0.001) and M-value (p. <. 0.001), without significant change in fasting glucose, HbA1c and adiponectin. In GHD children, M-value showed a significant but weak correlation with ISI Matsuda (rho 0.418, p = 0.047) at baseline, while no correlation with other parameters was found. After 12. months of GHT, M-value did not show any significant correlation with any other metabolic parameter analyzed. Conclusions: This study highlights the limit of the evaluation of insulin sensitivity performed through surrogate indices or circulating markers, which may lead to controversial data and do not correlate with the gold standard technique to evaluate insulin sensitivity

Prevalence and clinical features of polycystic ovarian syndrome in adolescents with previous childhood growth hormone deficiency.

BACKGROUND: Growth hormone (GH) plays a role in the regulation of ovarian function but there are limited data in women with GH deficiency (GHD). Our aim was to evaluate the features of polycystic ovarian syndrome (PCOS) in women with previous GHD. METHODS: Data of 22 adolescents previously GH-treated (group A) were compared with those of 22 women with classical PCOS (group B) and 20 controls (group C). RESULTS: Group A showed higher testosterone (p=0.048) and prevalence of menstrual irregularities (p<0.001) than group C. Compared to the group B, group A showed lower diastolic blood pressure (p=0.004), degree of hirsutism (p=0.005), testosterone (p=0.003) and prevalence of polycsytic ovaries (POC) morphology (p=0.024), with higher HDL-cholesterol (p=0.035) and 17-β-estradiol (p=0.009). CONCLUSIONS: Adolescents with previous GHD show a higher prevalence of PCOS than controls, but with milder metabolic and hormonal features than adolescents with classical PCOS. A careful long-term follow-up is advisable in these patients

Visceral Adiposity Index Is Associated with Insulin Sensitivity and Adipocytokine Levels in Newly Diagnosed Acromegalic Patients.

Context: The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of patients at metabolic risk. Objective: The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly. Patients: Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%). Outcome Measures: Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUCGH) during the oral glucose tolerance test, AUCCpeptide during a mixed-meal tolerance test, M value during euglycemic-hyperinsulinemic clamp, oral dispositional index (DIo), each component of the metabolic syndrome, leptin, adiponectin, TNF-α, and IL-6. Results: The VAI value was positively correlated with the age of patients (ρ = 0.408; P = 0.048), tumor volume (ρ = 0.638; P = 0.001), basal GH (ρ = 0.622; P = 0.001), nadir GH (ρ = 0.534; P = 0.007), AUCGH (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUCCpeptide (ρ = 0.715; p<0.001) and negatively with adiponectin (ρ = −0.766; P < 0.001), M value (ρ = −0.818; P < 0.001), and DIo (ρ = −0.512; P = 0.011). Patients with high VAI showed significantly higher basal GH levels (P = 0.018), AUCGH (P = 0.047), IGF-I (P = 0.047), AUCCpeptide (P = 0.018), lower M value (P < 0.001), DIo (P = 0.006), and adiponectin levels (P < 0.001), despite the absence of a significantly higher prevalence in the overt metabolic syndrome and glucose tolerance abnormalities. AUCGH proved to be the main independent factor influencing VAI. Conclusions: In acromegaly, VAI appears to be associated with disease activity, adiponectin levels, and insulin sensitivity and secretion and is influenced independently by GH levels. VAI could therefore be used as an easy and useful new tool in daily clinical practice for the assessment of early metabolic risk associated with active acromegal

Revaluation of the clinical and metabolic behavior of children with isolated growth hormone deficiency during GH treatment according to newly proposed note 39 of the Italian Medicines Agency (AIFA).

Purpose To evaluate the clinical and metabolic behavior of children with isolated growth hormone (GH)-deficiency (GHD), grouped according to the new AIFA criteria for the appropriateness of use and reimbursement of GH treatment in children. Methods The clinical and metabolic data of 310 prepubertal children (220 M, 90 F; mean age 10.8 years) grouped, according to new AIFA note 39, into group A (No 181 with a peak of GH 10 µg/L) were retrospectively analyzed. Group A and B, diagnosed as having GHD, were treated with GH for at least 24 months, while group C was analyzed only at baseline. Results At baseline, group A showed higher waist circumference than B (p=0.031) and C (p=0.041), while no difference in metabolic parameters was found between the 3 groups. After 12 and 24 months of treatment, group B showed lower height velocity (p<0.001 and p=0.049, respectively) than group A. As regards the metabolic parameters, both after 12 and 24 months of treatment, in group B we found higher fasting glucose (p<0.001 and p=0.020), insulin (p=0.002 and p=0.011), Homa-β (p=0.020 and p=0.015) and Homa-IR (both p=0.001) than group A, with concomitant lower QUICKI (both p<0.001) and HDL cholesterol (p=0.020 and p=0.011), without difference in other lipid parameters. The HbA1c levels, although always within the normal range, was found higher in group B than group A after 12 months (p=0.015). Conclusions Accordingly with the new AIFA criteria, the reduction of GH cut-off for GHD diagnosis can be supported by auxological and metabolic data. The real benefits from GH therapy in children with higher stimulated GH levels at diagnosis remains to better understand