GHD come predittore di sindrome metabolica

Il GH, la cui principale azione consiste nella stimolazione della crescita corporea, continua ad esercitare funzioni metaboliche in et\ue0 adulta, per cui l\u2019ormai riconosciuta \u201csindrome da deficit di GH (GHD) dell\u2019adulto\u201d configura un vero e proprio modello di sindrome metabolica (SM). La prevalenza di SM nel GHD \ue8 infatti significativamente pi\uf9 alta rispetto alla popolazione generale anche se ad oggi sono ancora limitati gli studi prospettici di lunga durata che hanno analizzato specificatamente la prevalenza di SM e delle sue individuali componenti in soggetti GHD. Le azioni metaboliche del GH sono tessuto-specifiche, esplicandosi prevalentemente a livello di fegato, tessuto adiposo, muscolo e pancreas. La mancanza di queste azioni determina di conseguenza le alterazioni metaboliche associate al GHD, che includono insulino-resistenza e vari gradi di alterazioni del metabolismo glucidico, obesit\ue0 viscerale, profilo lipidico aterogenico. Sui valori pressori invece il GH agisce in modo bivalente, con azione vasodilatatrice tramite la produzione di ossido nitrico, ma anche con azione sodio-ritentiva e di aumento del volume extracellulare, per cui la mancanza di queste azioni potrebbe spiegare la non univocit\ue0 dei dati sulla prevalenza di ipertensione arteriosa nel GHD

Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess

The interplay between vitamin D and the growth hormone (GH)/insulin-like growth factor (IGF)-I system is very complex and to date it is not fully understood. GH directly regulates renal 1 alpha-hydroxylase activity, although the action of GH in modulating vitamin D metabolism may also be IGF-I mediated. On the other hand, vitamin D increases circulating IGF-I and the vitamin D deficiency should be normalized before measurement of IGF-I concentrations to obtain reliable and unbiased IGF-I values. Indeed, linear growth after treatment of nutritional vitamin D deficiency seems to be mediated through activation of the GH/IGF-I axis and it suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and GH/IGF-I secretion. Vitamin D levels are commonly lower in patients with GH deficiency (GHD) than in controls, with a variable prevalence of insufficiency or deficiency, and this condition may worsen the already known cardiovascular and metabolic risk of GHD, although this finding is not common to all studies. In addition, data on the impact of GH treatment on vitamin D levels in GHD patients are quite conflicting. Conversely, in active acromegaly, a condition characterized by a chronic GH excess, both increased and decreased vitamin D levels have been highlighted, and the interplay between vitamin D and the GH/IGF-I axis becomes even more complicated when we consider the acromegaly treatment, both medical and surgical. The current review summarizes the available data on vitamin D in the main disorders of the GH/IGF-I axis, providing an overview of the current state of the art

Reduction in insulin sensitivity and inadequate \u3b2-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth hormone deficiency during 12 months of growth hormone treatment

Purpose: To evaluate the performance of various indexes of insulin sensitivity and secretion and to identify the most useful indicator of deterioration of glucose metabolism in a cohort of children with growth hormone (GH) deficiency (GHD) during GH treatment. Methods: In 73 GHD children (55 M, 18 F; mean age 10.5 years) at baseline and after 12 months of treatment, we evaluated a number of surrogate indexes of insulin secretion and sensitivity. In a subgroup of 11 children we also performed an euglycemic hyperinsulinemic clamp. Results: After 12 months, a significant increase in fasting glucose (p < 0.001) and HbA1c levels (p < 0.001) was documented, despite all children remained with a normal glucose tolerance. With regard the insulin secretion, Homa-\u3b2 did not show any significant change (p = 0.073), while oral disposition index (DIo) showed a significant decrease (p = 0.031). With regard the insulin sensitivity, Homa-IR significantly increased (p < 0.001) with a concomitant decrease in QUICKI (p < 0.001). ISI Matsuda showed a decrease, although not statistically significant (p = 0.069). In the subgroup of 11 children, the M value derived from clamp showed a significant decrease (p = 0.011) and a significant positive correlation was found between M value and ISI Matsuda both at baseline (\u3c1 0.950; p = 0.001) and after 12 months (\u3c1 0.980; p = 0.001) but not with Homa-IR and QUICKI. Conclusions: 12 months of GH treatment lead to a decrease in insulin sensitivity and impairment in insulin secretion relative to insulin sensitivity even without evident changes in glucose tolerance. DIo has proven to be the most useful indicator of deterioration of glucose metabolism even in cases in which the overt glucose abnormalities have not yet appeared

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51\u2009\ub1\u200913 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensitivity check index, insulin sensitivity index Matsuda, insulin-like growth factor-I and visceral adiposity index. At baseline growth hormone deficiency patients showed higher waist circumference (p\u2009<\u20090.001), low-density lipoprotein cholesterol (p\u2009<\u20090.001) and visceral adiposity index (p\u2009=\u20090.003) with lower insulin sensitivity index (p\u2009=\u20090.007) and high-density lipoprotein cholesterol (p\u2009=\u20090.001) than controls. During growth hormone treatment we observed a significant increase in insulin-like growth factor-I (p\u2009<\u20090.001), high-density lipoprotein (p\u2009<\u20090.001) with a trend toward increase in insulin sensitivity index (p\u2009=\u20090.055) and a significant decrease in total cholesterol (p\u2009<\u20090.001) and visceral adiposity index (p\u2009<\u20090.001), while no significant changes were observed in other clinical and metabolic parameters. The visceral adiposity index was the only parameter that significantly correlated with growth hormone peak at diagnosis (p\u2009<\u20090.001) and with insulin-like growth factor-I and insulin sensitivity index both at diagnosis (p\u2009=\u20090.009 and p\u2009<\u20090.001) and after 12 (p\u2009=\u20090.026 and p\u2009=\u20090.001) and 24 months (p\u2009<\u20090.001 and p\u2009=\u20090.001) of treatment. The visceral adiposity index, which has shown to be associated with both insulin-like growth factor-I and insulin sensitivity, proved to be the most reliable index of metabolic perturbation, among the most common indexes of adiposity assessment and a marker of benefit during treatment in adult growth hormone deficiency patients

Serum visfatin levels in acromegaly: Correlation with disease activity and metabolic alterations

Objective: The studies that have extensively evaluated the relation between adipokines and metabolic parameters in acromegaly treatment are quite discordant. We aimed to evaluate and correlate a set of selected adipokines, known to have a metabolic role, with the disease activity, metabolic status and treatment modalities. Design: Data of 56 consecutive acromegalic patients (31 M and 25 F; aged 54 \ub1 12 years), admitted to the section of Endocrinology of the University of Palermo during the years 2005-2014, including 16 newly diagnosed untreated (ND), 21 during therapy with somatostatin analogues (SA), 12 with pegvisomant (PE) and 7 after surgical treatment (SU), grouped into uncontrolled (group A: No. 33) and controlled (group B: No. 23) were evaluated. Anthropometric and metabolic parameters, insulin sensitivity indexes, visceral adiposity index (VAI), leptin, soluble leptin receptor, adiponectin, visfatin, resistin, adipsin and non-esterified fatty acids (NEFAs) were assessed. In a subgroup of 21 subjects, the insulin sensitivity index (M value) derived from euglycemic clamp was calculated. Results: Group A showed higher Homa-IR (p < 0.001), VAI (p < 0.001), triglycerides (p < 0.001), visfatin (p < 0.001), and NEFAs (p < 0.001) and lower ISI Matsuda (p < 0.001), M value (p < 0.001), HDL cholesterol (p < 0.001) and leptin (p < 0.001) than group B. ND patients showed higher VAI, triglycerides, Homa-IR, and visfatin and lower ISI Matsuda, M-value, and leptin compared to other groups (all p < 0.050), while no differences were found among SA, PE and SU patients. IGF-1 (p = 0.048), M-value (p = 0.0029) and VAI (p = 0.010) were independently associated with visfatin, while only ISI Matsuda (p = 0.019) was associated with leptin. Conclusions: In acromegaly visfatin could be considered a useful index of disease activity and metabolic alterations, such as insulin resistance and adipose dysfunction, regardless of the type of treatment

Correlation between Severity of Growth Hormone Deficiency and Thyroid Metabolism and Effects of Long-Term Growth Hormone Treatment on Thyroid Function in Children with Idiopathic Growth Hormone Deficiency.

BACKGROUND/AIM: The significance of changes in thyroid function in children during growth hormone (GH) treatment remains uncertain. We aimed to evaluate the impact of GH replacement on thyroid status in children with idiopathic GH deficiency (GHD). METHODS: Data of 105 GHD children (82 M, 23 F; aged 11.13 years) during a 36-month follow-up were analyzed. At diagnosis the areas under the curve of GH (AUCGH) were calculated during a GH-releasing hormone + arginine (GHRH-Arg) and insulin tolerance test. RESULTS: A significant \u394fT3 (p < 0.001) was documented at 12 months, without any further change at 24 and 36 months and without fT4 and TSH modifications. Grouping patients according to \u394fT3 at 12 months into those with lower (n = 80, 76%) or greater values than the 75th percentile (n = 25, 24%), the latter showed lower AUCGH and GH peak during a GHRH-Arg (p = 0.018 and 0.014, respectively) and insulin tolerance test (p = 0.023 and 0.020, respectively) at diagnosis. In addition, children with lower GH at diagnosis showed a greater \u394fT3 at 12 months (p = 0.030). CONCLUSIONS: In GHD children, GH treatment is associated with a significant increase in fT3 in the first 12 months, more pronounced in patients with more severe GHD, highlighting the strong correlation between severity of GHD and thyroid metabolism

Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

INTRODUCTION: Although liraglutide is widely recognized to have glycemic and extra-glycemic effects, few studies have compared these effects in relation to hypoglycemic treatment starting from the diagnosis of diabetes. We evaluated the effectiveness of liraglutide in reducing the Framingham risk score (FRS) and visceral adiposity index (VAI) in relation to first-line hypoglycemic treatment from diagnosis of type 2 diabetes, continued without any changes. METHODS: We selected 105 diabetic outpatients who were treated with liraglutide for at least 48 months as an add-on therapy to metformin alone (group A, n = 52) or insulin secretagogues (group B, n = 53) from diagnosis time. RESULTS: Although both groups showed a reduction in BMI, waist circumference, blood pressure, HbA1c and triglycerides, only group A showed a significant reduction in FRS (p &lt; 0.001) and VAI (p = 0.012) after 48 months. No significant intergroup difference was found for any parameters at either baseline or 48 months, with the exception of FRS at 48 months, lower in group A (p = 0.002), regardless of duration of disease, improvement in glycemic control and VAI. CONCLUSION: Our data show that during a 48-month follow-up liraglutide was more efficacious in reducing cardiovascular risk than when it was used as add-on therapy to the first-line therapy from diagnosis with metformin and not with insulin secretagogues

Corneal thickness in children with growth hormone deficiency: The effect of GH treatment.

Abstract OBJECTIVE: The eye represents a target site for GH action, although few data are available in patients with GH deficiency (GHD). Our aim was to evaluate central corneal thickness (CCT) and intraocular pressure (IOP) values in GHD children to assess the role played by GHD or GH treatment on these parameters. DESIGN: In 74 prepubertal GHD children (51M, 23F, aged 10.4\ub12.4years) we measured CCT and IOP before and after 12months of treatment. A baseline evaluation was also made in 50 healthy children matched for age, gender and body mass index. The study outcome considered CCT and IOP during treatment and their correlations with biochemical and auxological data. RESULTS: No difference in CCT and IOP between GHD children at baseline and controls was found (all p>0.005). GHD children after 12months of therapy showed greater CCT (564.7\ub113.1\u3bcm) than both baseline values (535.7\ub117\u3bcm; p<0.001) and control subjects (536.2\ub112.5\u3bcm; p<0.001), with a concomitantly higher corrected mean IOP (15.6\ub10.7mmHg; p<0.001) than both baseline (12.5\ub10.8mmHg; p<0.001) and controls (12.3\ub10.5mmHg; p<0.001), without correlation with auxological and biochemical parameters. CONCLUSIONS: 12months of GH treatment in children with GHD, regardless of auxological and biochemical data, affect CCT and IOP. Our findings suggest careful ocular evaluation in these patients to prevent undesirable side effects during the follow-up

Pasireotide versus pituitary surgery: a retrospective analysis of 12 months of treatment in patients with Cushing's disease

Pituitary surgery represents the first-line treatment for most patients with Cushing\u2019s disease (CD). In the case of surgery failure, additional treatment options are required. Pasireotide has shown favourable results in the first-line treatment of patients with CD, who are not candidates for surgery or in the second-line when surgery has failed. The aim of the current study is to compare the effects of surgery and pasireotide treatment in a cohort of patients with CD, and to evaluate the differences in response rate in terms of hormonal and clinical control, and improvement of metabolic complication

More favorable metabolic impact of three-times-weekly versus daily growth hormone (GH) treatment in na\uefve GH-deficient children

OBJECTIVE: Growth hormone treatment (GHT) is commonly administered daily, although pulsatile GH secretion is unlikely to be achieved. The auxological effect of a three-injections-per-week (TIW) regimen is controversial, while the metabolic effects have been never evaluated in children. The objective was to evaluate whether two different regimens of weekly injections could lead to similar auxological and metabolic effects in children with GH deficiency (GHD). DESIGN: 32 GHD children (25 males, mean age 10.5 \ub1 2.2 yr) were randomly assigned to receive daily (group A, No 16) or TIW (group B, No 16) GHT for 12 months. METHODS: Auxological parameters, insulin-like growth factor-I (IGF-I), glucose and insulin during OGTT, glycosylated hemoglobin (HbA1c), lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR) and the insulin sensitivity index (ISI). RESULTS: After 12 months, both groups showed a significant and comparable improvement in height (p<0.001) and IGF-I (p<0.001). As regards the metabolic parameters, in both groups we found a significant increase in fasting insulin (p<0.001 and p=0.026) and Homa-IR (p<0.001 and p=0.019). A significant increase in fasting glucose (p=0.001) and a decrease in ISI (p<0.001) and DIo (p=0.002) were only found in group A. CONCLUSIONS: The TIW regimen is effective and comparable with the daily regimen in improving auxological parameters and has a more favorable metabolic impact in GHD children (www.ClinicalTrials.gov. NCT03033121)