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Defects of the GNAS gene have been mainly associated with pseudohypoparathyroidism Ia. To date, pathogenic missense, frameshift, non-sense and splicing variants have been described in all the 13 exons of the GNAS gene. Of them, a specific mutation, namely the 4 bp deletion c.565_568delGACT, is currently considered a mutation hotspot. Recent articles performed genotype-phenotype correlations in patients with GNAS -related pseudohypoparathyroidism Ia (PHP1a) but a specific focus on this hotspot is still lacking. We reported two cases, from our department, of PHP1a associated with c.565_568delGACT deletion and performed a literature review of all the previously reported cases of the 4 bp deletion hotspot. We found a higher prevalence of brachydactyly, round face, intellectual disability and subcutaneous/heterotopic ossifications in patients with the c.565_568delGACT as compared to the other variants in the GNAS gene. The present study highlights the different prevalence of some clinical features in patients with the c.565_568delGACT variant in the GNAS gene, suggesting the possibility of a personalized diagnostic follow-up and surveillance for these patients.

Children born small for gestational age (SGA) are defined as those having birth weight and/or length below -2 SD for gestational age. In approximately 90% of cases, SGA children experience catch-up growth in the first two years of life and a subsequent regular growth rate, reaching normal adult height. However, in the remaining 10% of cases, SGA children fail to have catch-up growth, showing persistent short stature and a constantly impaired growth rate, leading to decreased adult height compared with both general population and their mid-parental height. Therefore, in these children GH treatment may be indicated to improve growth outcome. As it can be started in most countries from the age of 4 years and is usually recommended until the completion of puberty, long-term GH treatment in SGA children (namely, longer than three years) showed a persistent improvement in height and an initial improvement in growth rate in the first year of treatment, followed by a stable, regular growth rate over time. In the present article, we systematically reviewed the currently available reports about efficacy of long-term GH treatment in SGA children, with a particular focus on growth rate over time and adult height., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Children born Small for Gestational Age (SGA) without early catch-up growth may show impaired growth rate, adult height, and metabolic profile [1]. Growth Hormone (GH) is recommended for their treatment, and it has been shown to have positive effects on growth and metabolic profile and good tolerability [2]., Objective: The study aimed to evaluate the auxological and metabolic effects and safety of GH treatment in SGA children., Methods: 34 SGA children (15 F, 19 M; mean age: 8.72 ± 2.48 yrs) treated with GH (starting dosage: 32.24 ± 2.88 mcg/kg/die) were evaluated every six months for 24 months with growth and metabolic parameters., Results: After two years, SGA children showed a significant improvement in height, weight, and growth rate, already evident after six months (p < 0.001), with a constant, significant improvement in height throughout the treatment (p ≤ 0.03 T0 vs. T12, T12 vs. T24). Conversely, although significantly higher than baseline at each visit (p < 0.001), the growth rate significantly decreased from 6 to 18 months (p ≤ 0.015 T6 vs. T12, T12 vs. T18). During the follow-up, an increase in glycemia (p ≤ 0.042 vs. T12, T18) and urycemia (p ≤ 0.01 vs. T12, T18, and T24) and a decrease in AST (p ≤ 0.021 vs. T12, T18, and T24) and LDL cholesterol (p = 0.03 vs. T24) were observed. Overall, treatment was found to be well tolerated, with poor compliance being the most frequent adverse event (11.8%) and no reported hyperglycemia., Conclusion: In conclusion, GH can be considered an effective, safe treatment in SGA children, improving height and growth rate, although proper metabolic follow-up is required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rationale: Children born small for gestational age (SGA) not showing catch-up during the first two years of life reportedly show an impaired growth rate and adult height, as well as a worse metabolic outcome, mainly in terms of glycemic and lipid profile, compared to general population. In SGA children with short stature, treatment with recombinant growth hormone (GH) is currently recommended until adolescence; therefore, it may last long-term., Study Methods: The aim of the current study was to evaluate the auxological and metabolic effects and the safety of long-term recombinant GH treatment in SGA children. The study included 15 SGA children (5 F, 10 M; mean age: 6.78 yrs) treated with GH for at least 48 months. Growth and metabolic parameters, including glycemic and lipid profile, transaminases, and urycemia, were collected every six months., Results: Compared to baseline, SGA children showed a significant improvement in height, weight, and growth rate after four yaers of treatment with GH (p ≤ 0.002), being already evident after six months of treatment (p < 0.001). Noteworthy, patients showed a constant, significant improvement in height throughout the treatment, as it was significantly higher at each follow-up compared to the previous one, until 42 months of treatment, except at 30 months of treatment (p < 0.001 T6VST12; p < 0.01 T12VST18, T18VST24; p < 0.05 T30VST36, T36VST42). Considering metabolic parameters, compared to baseline, a recurring increase in glycemia (p ≤ 0.028 vs T30, T36, and T48) and decrease in AST (p ≤ 0.035 vs T36, T42, and T48) and an occasional decrease in LDL cholesterol (p ≤ 0.04 vs T24 and T42) and triglycerides (p = 0.008 vs T18) and increase in urycemia (p = 0.034 vs T42). Considering safety profile, treatment was well tolerated, as the most frequently reported adverse event was poor compliance (20%); no hyperglycemia, hypercholesterolemia or hyperstransaminasemia occurred throughout the treatment, CONCLUSIONS: Long-term GH treatment showed to be effective in improving height and growth rate in SGA children, with a positive impact of metabolic profile and a safety profile, although glycemia should be carefully monitored over time., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Primary adrenal insufficiency (PAI) is an endocrine disorder characterized by direct adrenal failure , with consequent glucocorticoid, and eventually mineralocorticoid, deficiency. In children, the main cause of PAI is congenital adrenal hyperplasia (CAH), due to a loss of function of adrenal steroidogenic enzymes, but also rarer forms, including autoimmune polyglandular syndrome, adrenoleucodistrophy, adrenal hypoplasia congenita, familial glucocorticoid deficiency, and Allgrove's Syndrome, may be observed. In PAI children, growth alterations represent a major issue, as both inadequate and excessive glucocorticoid replacement treatment may lead to reduced growth rate and adult height impairment. However, growth abnormalities are poorly studied in rare forms of paediatric PAI, and specific studies on growth rate in these children are currently lacking. In the present review, the currently available evidence on growth alterations in children with rare PAI forms will be summarized, with a major focus on comorbidities with a potential impact on patients' growth rate., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment., Objective: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment., Methods: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression., Results: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment., Conclusion: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.

Background: Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine., Objectives: In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls., Methods: An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry., Results: Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (p<0.05). Moreover, no difference in Bisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose., Conclusion: BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this review is to provide a general overview of the possible associations among the vitamin D status, air pollution and obesity. Sunlight exposure accounts in humans for more than 90 % of the production of vitamin D. Among emerging factors influencing sunlight-induced synthesis of vitamin D, prospective and observational studies proved that air pollution constitutes an independent risk factor in the pathogenesis of vitamin D hypovitaminosis. In addition, environmental pollutants can affect risk of obesity when inhaled, in combination with unhealthy diet and lifestyle. In turn, obesity is closely associated with a low vitamin D status and many possible mechanisms have been proposed to explain this association. The associations of air pollution with low vitamin D status on the hand and with obesity on the other hand, could provide a rationale for considering obesity as a further link between air pollution and low vitamin D status. In this respect, a vicious cycle could operate among low vitamin D status, air pollution, and obesity, with additive detrimental effects on cardio-metabolic risk in obese individuals. Besides vitamin D supplementation, nutrient combination, used to maximize the protective effects against air pollution, might also contribute to improve the vitamin D status by attenuating the "obesogen" effects of air pollution.

Low vitamin D status and obesity have concomitantly reached epidemic levels worldwide. Up to now the direction of the association between low vitamin D status and obesity, the exact mechanisms responsible for this association and the clinical usefulness to increase vitamin D status for reducing adiposity still warrant further evaluation. The aim of the present review was to examine the current evidence linking low vitamin D status and obesity in relation to the role of the nutritionist. On the one side, considering obesity as a causal factor, low sun exposure in obese individuals due to their sedentary lifestyle and less outdoor activity, vitamin D sequestration in adipose tissue, and volumetric dilution of ingested or cutaneously synthesized vitamin D 3 in the large fat mass of obese patients, might represent some of the factors playing a major role in the pathogenesis of the low vitamin D status. On the other side, the expression of both vitamin D 3 receptors and enzymes responsible for vitamin D 3 metabolism in adipocytes depicted a role for the low vitamin D status per se in the development of obesity by modulating adipocyte differentiation and lipid metabolism. Nutritionists need to accurately address the aspects influencing the low vitamin D status in obesity and the vitamin D supplementation in obese individuals.

Psoriasis is a chronic immune-mediated inflammatory skin disease. Psoriasis lesions are characterized by hyper-proliferation of epidermal keratinocytes associated with inflammatory cellular infiltrate in both dermis and epidermis. The epidermis is the natural source of vitamin D synthesis by sunlight action. Recently, a role for vitamin D in the pathogenesis of different skin diseases, including psoriasis, has been reported. Indeed, significant associations between low vitamin D status and psoriasis have been systematically observed. Due to its role in proliferation and maturation of keratinocytes, vitamin D has become an important local therapeutic option in the treatment of psoriasis. To date, the successful treatment based on adequate dietary intake of vitamin D or oral vitamin D supplementation in psoriasis represent an unmet clinical need and the evidence of its beneficial effects remains still controversial. This information is important either for Dermatologists and Nutritionists to increases the knowledge on the possible bi-directional relationships between low vitamin D status and psoriasis and on the potential usefulness of vitamin D in psoriasis with the aim not only to reduce its clinical severity, but also for delineating the risk profile for co-morbidities cardiac risk factors that may result from psoriasis. In the current review, we analyzed the possible bi-directional links between psoriatic disease and vitamin D.

Background: Nutrition is an environmental factor affecting bone health. Nutrition is considered essential to achieve and maintain optimal bone mass. Mediterranean diet (MD) has shown to prevent bone disease. Aim of this study is to investigate the relationship between bone health status and adherence the MD., Methods: Four-hundred eighteen healthy people (105 males and 313 females, age 50 ± 14 years) were recruited in the outdoor hospital of the "Campus Salute Onlus" held in Piazza del Plebiscito in Naples, October 17-20th 2013 and 09-11th October 2014. All subjects underwent clinical assessment, calcaneal quantitative ultrasound (QUS) scanner and PREvención con DIeta MEDiterránea (PREDIMED) questionnaire., Results: Globally, prevalence of osteoporosis and osteopenia were 7.7 and 46.0%, respectively. The majority of subjects (60.5%) had an average score (score 6-9) of adherence to MD. The T-score showed positive correlation with PREDIMED score (r = 0.250, p < 0.001). The higher T-scores were positively associated with a higher consumption of extra-virgin olive oil (EVOO), vegetables, fruits, legumes, and fish and negatively associated with consumption of red meat. The higher T-scores were positively associated with the highest odds of PREDIMED scores (higher adherence) (OR 6.91, IC 6.27-7.61, p < 0.001). Multiple regression analysis models indicated that, among the single food items investigated, high T-score can be predicted by consumption of EVOO (p < 0.001), fish (p < 0.001) and fruit (p = 0.002) intake. A PREDIMED score of 3 was found to be predictive for a low T-score (α = 0.05, R-squared index = 0.417)., Conclusions: The results demonstrate a positive correlation between bone health status and adherence to MD, suggesting that a high adherence to MD promotes bone health. The observations here reported confirmed that a specific dietary approach, such as MD, can represent a modifiable environmental factor for osteoporosis' prevention.

The Mediterranean diet is a healthy dietary pattern known to actively modulate the cell membrane properties. Phase angle (PhA) is a direct measure by Bioelectrical Impedance Analysis (BIA) used as marker of cell membrane integrity. Both food behaviour and PhA are influenced by age, sex and body weight. The aim of this study was to cross-sectionally evaluate the association between the adherence to Mediterranean diet and PhA in 1013 healthy adult patients stratified according to sex, age, and body mass index (BMI). The adherence to the Mediterranean diet was evaluated using the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. PhA was calculated by BIA phase-sensitive system (50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy Akern). In both sexes, at ROC analysis a PREDIMED score ≥ 6 predicted a PhA beyond the median value. At the multivariate analysis, among PREDIMED score, age, and BMI, the PREDIMED score was the major determinant of PhA, explaining 44.5% and 47.3% of PhA variability, in males and females respectively ( p < 0.001). A novel association was reported between the adherence to the Mediterranean diet and PhA, independently of sex, age, and body weight. This association uncovered a new potential benefit of the Mediterranean diet on health outcomes, as in both sexes higher adherence to the Mediterranean diet was associated to larger PhAs, as expression of cell membrane integrity.

Background & Aims: Nutrition is the major environmental factor that influences the risk of developing pathologies, such as obesity. Although a number of recent reviews pinpoint a protective effects of milk on body weight and obesity related co-morbidities, an inaccurate estimate of milk might contribute to hamper its beneficial effects on health outcomes. Seven-day food records provide prospective food intake data, reducing recall bias and providing extra details about specific food items. Milk intake stimulates the somatotropic axis at multiple levels by increasing both growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. On the other hand, obesity is associated with reduced spontaneous and stimulated GH secretion and basal IGF-1 levels. Aim of this study was to evaluate the milk consumption by using the 7-days food record in obese individuals and to investigate the association between milk intake and GH secretory status in these subjects., Methods: Cross-sectional observational study carried out on 281 adult individuals (200 women and 81 men, aged 18-74 years) with moderate-severe obesity (BMI 35.2-69.4 kg/m 2 ). Baseline milk intake data were collected using a 7 day food record. Anthropometric measurements and biochemical profile were determined. The GH/IGF-1 axis was evaluated by peak GH response after GHRH + ARGININE and IGF-1 standard deviation score (SDS)., Results: The majority of individuals (72.2%) reported consuming milk; 250 mL low-fat milk was the most frequently serving of milk consumed, while no subjects reported to consume whole milk. Milk consumers vs no milk consumers presented the better anthropometric measurements and metabolic profile. At the bivariate proportional odds ratio model, after adjusting for BMI, age and gender, milk consumption was associated the better GH status (OR = 0.60; p < 0.001). Among milk consumers, subjects consuming 250 mL reduced-fat milk vs 250 mL low-fat milk presented the better anthropometric measurements and metabolic profile. At the bivariate proportional odds ratio model, after adjusting for BMI, age and gender, the consume of 250 mL reduced-fat milk was associated better GH status (OR = 0.54; p = 0.003)., Conclusions: A novel positive association between milk consumption, GH status, and metabolic profile in obese individuals was evidenced. Regardless of the pathogenetic mechanisms, this novel association might be relevant in a context where commonly obese individuals skip breakfast, and suggests the need of a growing cooperation between Nutritionists and Endocrinologists in the management of the obese patients., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is a growing body of evidence indicating that patients with adult GH deficiency (GHD) are characterized by a cluster of traditional and emerging cardiovascular risk factors and markers, which can significantly increase their cardiovascular morbidity and mortality possibly linked to aberrations in GH status. Patients with adult GHD present multiple different cardiovascular abnormalities. In addition, cardiovascular risk in adult GHD is increased due to altered body composition, abnormal lipid profile, insulin resistance and impaired glucose metabolism. Cardiovascular risk factors can be reversed, at least partially, after GH replacement. However, evidence on the effects of GH replacement on cardiovascular events and mortality is too limited in adult GHD patients. Aim of this review is to provide an at-a-glance overview of the role of the GH/IGF-I on the cardiovascular system and the state of art of the effects of GH replacement on cardiovascular system., (Copyright © 2017. Published by Elsevier Ltd.)

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity.

Psoriasis is a common, chronic, immune-mediated skin disease with systemic pro-inflammatory activation, where both environmental and genetic factors contribute to its pathogenesis. Among the risk factors for psoriasis, evidence is accumulating that nutrition plays a major role, per se, in psoriasis pathogenesis. In particular, body weight, nutrition, and diet may exacerbate the clinical manifestations, or even trigger the disease. Understanding the epidemiological relationship between obesity and psoriasis is also important for delineating the risk profile for the obesity-related comorbidities commonly found among psoriatic patients. Moreover, obesity can affect both drug's pharmacokinetics and pharmacodynamics. Additionally, the overall beneficial effects on the obesity-associated comorbidities, clinical recommendations to reduce weight and to adopt a healthy lifestyle could improve the psoriasis severity, particularly in those patients with moderate to severe disease, thus exerting additional therapeutic effects in the conventional treatment in obese patients with psoriasis. Education regarding modifiable environmental factors is essential in the treatment of this disease and represents one of the primary interventions that can affect the prognosis of patients with psoriasis. The goal is to make psoriatic patients and health care providers aware of beneficial dietary interventions. The aim of this review is to assess the relevance of the environmental factors as modifiable risk factors in psoriasis pathogenesis, with particular regard to the involvement of obesity and nutrition in the management of psoriasis, providing also specific nutrition recommendations.

Background: Obesity, metabolic syndrome (MetS), and psoriasis, largely driven by environmental factors, show multiple bidirectional associations, with important metabolic implications in psoriatic patients. Besides body mass index (BMI) as a measure of obesity, data on phase angle (PhA), a direct measure by bioelectrical impedance analysis (BIA), used as a marker of cellular health and a predictor of morbidity and mortality in various diseases, are still lacking in psoriasis. In this case-control, cross-sectional study, we investigated the PhA in 180 pairs of adult psoriatic patients and healthy controls, evaluating also the potential use of the PhA as marker of the clinical severity, the quality of life, and the presence of the MetS in psoriatic patients., Methods: Anthropometric measures, metabolic profile and bioelectrical variables were evaluated. The clinical severity was assessed by standardized psoriasis area and severity index (PASI) score and c-reactive protein (CRP) levels, and the quality of life was evaluated by dermatology life quality index (DLQI). MetS was diagnosed according to Adult Treatment Panel III., Results: Psoriatic patients presented smaller PhA (p < 0.001) and higher prevalence MetS compared with controls. The PhA was significantly associated with number of parameters of MetS in both groups (p < 0.001). After adjusting for BMI, this association remained significant in psoriatic patients only (p < 0.001). Among psoriatic patients, the PhA was the major index value for the diagnosis of MetS (OR 5.87, 95 % CI 5.07-6.79) and was inversely associated with both PASI score and DLQI, independently of BMI (p < 0.001). At multiple regression analysis, the PhA well predicted the PASI score and DLQI. Based on ROC curves, the most sensitive and specific cutoffs of PhA to predict the highest PASI score and the lowest DQLI were ≤4.8° and ≤4.9°, respectively., Conclusions: We reported that psoriatic patients presented small PhAs, with a novel association between PhA, clinical severity, quality of life in psoriatic patients, and MetS. Further studies are required to validate the PhA's prognostic ability in assessing the clinical severity and MetS in psoriatic patients.

Hypovitaminosis D represent an environmental risk factors for cardiovascular (CV) disease. To investigate the prevalence of hypovitaminosis D and the correlation between GH/IGF-I deficiency and hypovitaminosis D with CV risk in GH deficiency (GHD) patients. A link between these hormones has been shown. Forty-one hypopituitaric patients with GHD (22 males, age 18-84 years) and 41 controls were enrolled in the study. Anthropometric parameters, blood pressure, glucose and lipid profile, parathyroid hormone (PTH), 25(OH) vitamin D (vitamin D), metabolic syndrome (MS), GH peak after GHRH + ARG, IGF-I, and standard deviation score (SDS) of IGF-I (zIGF-I) were assessed. Vitamin D levels were lower in patients than in controls (21.3 ± 12.3 vs. 28.2 ± 9.4, p = 0.006). Deficiency was found in 51 % of patients versus 14.6 % of controls (p < 0.01), insufficiency in 26.8 versus 41.4 % (p = 0.269) and normal vitamin D levels in 21.9 versus 43.9 % (p = 0.060). The prevalence of dyslipidemia was 51.2 % in patients versus 12.1 % in controls (p < 0.001), type 2 diabetes mellitus (DM) was 7.3 versus 17 % (p = 0.292), hypertension was 44 versus 22 % (p = 0.060), and MS was 17 versus 14.6 % (p = 0.957). In patients, an association was found between the presence of hypovitaminosis D and the prevalence of dyslipidemia, hypertension and MS and between zIGF-I and the prevalence of hypertension. Hypovitaminosis D was the most powerful predictor of the prevalence of dyslipidemia and hypertension. GHD patients have an increased prevalence of hypovitaminosis D compared with controls. The presence of hypovitaminosis D was the most powerful predictor of the prevalence of dyslipidemia and hypertension in GHD patients, suggesting the involvement of both factors in the CV risk in these patients.

The aim of the study is to clarify the relationship between adipose tissue dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor (IGF)-I secretion in healthy adult subjects. We investigated the metabolic profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I levels, and visceral adiposity index (VAI). Anthropometric measures, lipid profile, and glucose and insulin levels during oral glucose tolerance test, Homa-IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were analyzed. The subjects with high VAI showed lower GH peak (22.8 ± 11.1 vs. 42.2 ± 21.3 µg/L; p = 0.049) and lower IGF-I (presented as IGF-I under normal range, UNR) (0.54 ± 0.14 vs. 0.64 ± 0.12; p = 0.005) than group with normal VAI. ROC curve analysis identified the cut-off, able to detect subjects with high VAI, i.e., 31.8 µg/L for GH peak and 0.63 for IGF-1 UNR. The subjects with GH peak and IGF-I UNR under the cut-off showed significantly higher levels of VAI, systolic and diastolic blood pressure, glucose and insulin levels, Homa-IR, and lower ISI Matsuda, with a concomitant worse lipid profile (all p < 0.001). A strong relationship between GH axis, VAI and metabolic risk has been demonstrated. A percentage of apparently healthy subjects show a degree of visceral adipose dysfunction associated with GH and IGF-I levels that do not meet the criteria of overt GH deficiency (GHD). Long-term prospective studies could help to clarify and confirm whether a hypothetical condition of subclinical GHD could be taken into account as a new clinical entity.

Background: Many studies have evaluated the role of individual nutrients on the development of psoriasis. However, only few studies have investigated the effect of a healthy eating pattern, such as the Mediterranean diet. In this study, we aimed to investigate the relationship between adherence to the Mediterranean diet, the body composition and the severity of psoriasis in a group of naïve-treatment patients with psoriasis., Methods: This is a cross-sectional case-control observational study. Sixty-two patients (49 males and 13 females, mean age: 50.2±10.5yrs) affected with mild-to-severe psoriasis were consecutively enrolled. Sixty-two age-, sex- and body mass index (BMI)-matched healthy subjects served as control group. A validated 14-item questionnaire (PREDIMED: PREvención con DIeta MEDiterránea) was used for the assessment of adherence to the Mediterranean diet. The severity of psoriasis was by assessed by standardized Psoriasis Area and Severity Index (PASI) score and C-reactive protein (CRP) levels. Body composition was analyzed with bioelectrical impedance analysis., Results: A higher percentage of psoriatic patients had a lower PREDIMED score compared to the control group (30.6% vs 4.8%). PASI score was significantly associated with the percentage of fat mass (FM%) and CRP levels. PASI score and CRP levels were significantly associated with the dietary components included in the PREDIMED questionnaire or with the PREDIMED score. At multiple regression analysis, the major predictor of PASI score were FM among BIA parameters, (r(2)=0.537, β=0.740, p<0.001), and FM (r(2)=0.537, β=0.603, p<0.001) and PREDIMED score (r(2)=0.599, β=-0.296, p=0.007) among anthropometric measures, FM and PREDIMED score. Finally, among all items of the PREDIMED questionnaire, EVOO (r(2)=0.548, β=-0.741, p<0.001), and fish consumption (r(2)=0.139, β=-0.372, p=0.005) have an independent predictive value for PASI score and CRP levels., Conclusions: This is the first study to evaluate the association between adherence to the Mediterranean diet and the severity of psoriasis. Moreover, our study highlights the usefulness of the assessment of body composition by bioelectrical impedance analysis in the evaluation of the psoriatic patients.

Objective: Primary empty sella (PES) is a frequent anatomical condition rarely causing pituitary dysfunction. We assessed cardiovascular risk in a cohort of PES patients referred to Endocrine Units., Design: The study was performed in three Italian tertiary referral centres. We evaluated pituitary function and cardiovascular risk, on the basis of lipid and glucose metabolism parameters and of Framingham score (FS), in 94 consecutive patients with PES diagnosis and in 94 gender, age and BMI matched controls., Patients: Pituitary function was normal in 30 patients (group A), whereas a single or multiple pituitary hormone deficiency was demonstrated in 64 (group B). Growth hormone deficiency (GHD) was diagnosed in 56, central hypothyroidism in 35, hypogonadotropic hypogonadism in 32 and central hypoadrenalism in 24 cases., Results: Framingham score was higher and glucose and lipid profile were worse in PES patients than in controls. Cardiovascular risk parameters were not different between group A and B. In group B, increased cardiovascular risk was associated with hypothyroidism and hypogonadism, but not with GHD. In group A, cardiovascular risk was higher and FT3 and FT4 levels were lower than in controls. Moreover, PES patients stratified for BMI showed a worse glucose and lipid profile and (in the overweight subgroup) higher FS than matched controls., Conclusions: Primary empty sella patients show increased cardiovascular risk, regardless of BMI. A worse lipid and glucose profile and higher FS were associated with secondary hypothyroidism, even subclinical, as well as hypogonadism., (© 2012 John Wiley & Sons Ltd.)

The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular abnormalities and restores the normal life expectancy.

Aging is associated with decay in the somatotroph axis, that has been considered to cause many of the catabolic sequelae of normal aging. The physiological changes that the human body undergoes during aging are similar to those observed in GH deficiency (GHD). Changes of aging are represented by increased fat mass, increased cardiovascular risk, reduced muscle mass, reduced exercise tolerance, decreased strength and impaired quality of life. Some authors conjecture that the elderly could be GH deficient and would benefit from GH treatment. However, the endocrine pattern of aging is distinct from the decrease of GH/IGF-I levels associated with hypopituitarism, although there is not sufficient evidence for a clear therapeutic role of GH treatment during somatopause. So, further studies are needed to evaluate the real benefit of somatotropic treatment in aging. This review is focused on the effects of the somatopause and summarize the potentials for a therapeutic role of the recombinant human GH (rhGH) or of GH secretagogues in aging.

Background: The aim of this observational study was to determine, in a retrospective analysis, whether growth hormone (GH) and insulin-like growth factor-1 (IGF-1) at baseline or changes in the GH/IGF-1 axis after laparoscopic adjustable gastric banding (LAGB) is associated with weight loss and body composition changes in severely obese nondiabetic patients., Methods: Weight loss (expressed as percent excess weight loss [EWL%]), anthropometry, body composition by bioelectrical impedance analysis (BIA), serum IGF-1, and GH peak after GH-releasing hormone (GHRH) plus arginine (ARG) test were measured and expressed as standard deviation scores (SDS) of reference values in 104 women and 36 men, age (mean +/- SD) 34 +/- 11 and 30.2 +/- 11 years, and BMI 44 +/- 5.7 and 39 +/- 3.2, respectively, before and 6 months after LAGB., Results: After LAGB, 25% of women and 22.5% of men had GH deficiency, while 30.8% of women and 33.3% of men had IGF-1 deficiency or insufficiency. The median EWL was 36.8% in women and 40.0% in men. In both genders, percent decrease of waist circumference, EWL, and fat mass (FM) and percent increase of fat-free mass (FFM) was greater in patients with normal GH secretion and IGF-1 levels. The GH peak after GHRH + ARG, IGF-1 levels, and IGF-1 SDS were inversely correlated with EWL% (r = -0.50, r = -0.53, and r = -0.42, respectively; p < 0.0001) and percent FM (r = -0.41, r = -0.36, and r = -0.35, respectively; p < 0.0001). In stepwise linear regression analysis, the GH peak after GHRH + ARG was the major determinant of EWL% (p < 0.0001) and FM (p = 0.001)., Conclusions: The efficacy of LAGB was greater in the patients with a normal GH response to GHRH + ARG and with normal IGF-1 levels. The percent of FM, FFM, and EWL were significantly correlated with the GH response to GHRH + ARG and with IGF-1 levels.

Objective: The objective of the study was to reevaluate the diagnostic accuracy of GH peak after GHRH plus arginine test (GHRH+ARG) according to patients' age, body mass index (BMI), and waist circumference to diagnose GH deficiency (GHD)., Outcome Measures: GH peak after GHRH+ARG and IGF-I levels reported as sd score., Subjects: Subjects included 408 controls (218 women, 190 men, aged 15-80 yr) and 374 patients with hypopituitarism (167 women, 207 men, aged 16-83 yr)., Results: In the (elderly) healthy subjects 15-25 yr old (young), 26-65 yr old (adults) and older than 65 yr, GH cutoffs were 15.6, 11.7, and 8.5 microg/liter, 11.8, 8.1, and 5.5 microg/liter, and 9.2, 6.1, and 4.0 microg/liter, respectively, in the lean, overweight, and obese subjects. Waist circumference was the best predictor of GH peak (t = -7.6, P < 0.0001) followed by BMI (t = -6.7, P < 0.0001) and age (t = -5.7, P < 0.0001). Based on the old (<9.1 microg/liter) and new GH cutoff, 286 (76.5%) and 276 (73.8%) of 374 hypopituitary patients had severe GHD. The receiving-operator characteristic analysis showed GH cutoffs in line with the third percentile or slightly higher results so that the prevalence of GHD increased to 90.1%., Conclusions: The results of the current study show that waist circumference and BMI are the strongest predictors of GH peak after GHRH+ARG followed by age. However, the old cutoff value of 9.0 microg/liter was in line with the new cutoffs in 95% of patients.

Context: GH secretion is reduced in obese subjects and increases after body weight loss. It is still unclear if changes in the GH/IGF-I axis after laparoscopic-adjustable silicone gastric banding (LASGB) are associated with changes of body composition., Objective: To analyse the relationships between changes in the GH/IGF-I axis and those of body weight and composition before and after LASGB., Design: Observational, prospective., Setting: University 'Federico II' of Naples (Italy)., Patients: Seventy-two severely obese females (BMI: 44.9 +/- 4.68; mean age: 33.1 +/- 11.34 years) were studied., Main Outcome Measures: GH peak after GHRH plus arginine test, IGF-I, IGFBP-3 and ALS levels, fat mass (FM) and free fat mass (FFM) (by Bioelectrical Impedance Analysis) at baseline and 6 months after LASGB. The change in percentage of individual variables was calculated as well as that of excess of body weight loss (EBWL%). The FM%, FFM% and EBWL% were correlated with peak GH and IGF-I levels changes., Results: At baseline, GH deficiency (GHD) (GH peak = 4.1 microg/l) was found in 22 patients (31%), 16 of them also had IGF-I deficiency (< -2SDS). IGF-I levels were inversely correlated with waist circumference (r = -0.72, P < 0.001) and FM% (r = -0.75, P < 0.001). Post-LASGB the patients were classified as follows: group (1) GH and IGF-I sufficient (n = 44; 61.1%); group (2) GH and IGF-I deficient (n = 14; 19.4%) and group (3) GH sufficient and IGF-I deficient (n = 14; 19.4%). The percentage changes of EWBL (P < 0.05, P = 0.051, respectively) and FM (P < 0.001, P < 0.01, respectively) were lower in groups (2) and (3) than in group (1). At the stepwise linear regression analysis, postoperative IGF-I levels were the strongest determinant of percent changes of FM (P < 0.0001), of FFM (P = 0.009) and of EBWL (P < 0.0001)., Conclusions: IGF-I levels is the most sensitive to unfavourable changes in body composition 6 months after LASGB making investigation of the somatotropic axis useful in the evaluation of bariatric surgery outcomes.

Background: Severe GH deficiency (GHD) is associated with, increased cardiovascular risk and intima-media thickness (IMT) at major arteries., Objective: The objective of the study was to investigate the 5-yr effects of GH replacement on common carotid IMT and insulin resistance syndrome (IRS) (at least two of the following: triglycerides levels > or = 1.7 mmol/liter, high-density lipoprotein-cholesterol levels < or = 1.0 mmol/liter, blood pressure above 130/85 mm Hg, fasting glucose 6.1-7 or 2 hr after glucose 7.7-11.1 mmol/liter)., Design: This was an interventional, open, prospective, controlled study., Patients: Patients included 35 men with severe GHD and 35 age-matched healthy men as controls., Intervention: All patients received standard replacement therapy; GH replacement was added in 22 patients (group A) and refused by 13 others (group B)., Measurements: Five-year changes in IMT and IRS prevalence were measured., Results: At baseline, IMT was higher in the patients with (P < 0.001) and without IRS (P = 0.004) than in controls. Eighteen patients (51.4%) and two controls (5.7%; P < 0.0001) had IRS. At study end, use of lipid-lowering drugs (92.3, vs. 13.6 and 34.3%, P < 0.0001), glucose-lowering drugs (69.2 vs. 31.4 and 22.7%; P = 0.016), and antihypertensive drugs (61.5 vs. 20.0 and 4.5%; P < 0.0001) was higher in group B patients than controls and group A patients. IGF-I levels normalized in all group A patients and remained lower than -1 sd score in 77% of group B patients. IMT significantly decreased only in group A and significantly increased in controls and nonsignificantly in group B patients. IRS prevalence significantly reduced only in group A patients., Conclusions: Severely hypopituitary GHD men have more frequently increased IMT at common carotid arteries and IRS than controls. After 5 years, only in GH replaced patients, IMT and prevalence of IRS decreased.

Obesity is characterized by abnormal GH secretion, with GH levels reduced up to levels that are comparable to those found in adult patients with organic GH deficiency (GHD). Despite the marked GH insufficiency, obese patients with no evidence of pituitary disease have generally normal levels of total IGF-I but increased levels of free IGF-I. Although the mechanism of the low GH in obesity is not completely understood nor is it clear whether its relationship with visceral adiposity is causal, it is widely accepted that the low GH secretory state in obesity is reversible since it is completely reversed by the normalization of body weight. Since overweight and obesity might affect the GH response to all provocative stimuli, particular attention has been recently paid to the confounding effect of body weight on the interpretation of GH stimulating tests and appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults. As the definition of appropriate criteria for the correct diagnosis of GHD in obesity is still debated, and the beneficial effects of chronic recombinant human GH replacement on obese individuals have not been definitely proved yet, further studies are therefore mandatory to confirm the real effectiveness of GH supplementation in conditions associated with a blunted GH secretion without organic hypopituitarism and to understand the physiological relevance of "functional" GHD on the pathogenesis of the multiple maladaptative endocrine changes involved in the pathogenesis of obesity.

GH deficiency (GHD) in adults is accompanied by reduced bone mass that may revert only after 2 yr of GH replacement. However, it is unclear whether the gender may modify bone responsiveness to GH replacement in adults. In this study we have evaluated whether bone mineral density (BMD) and turnover improve after GH replacement according to patients' gender. BMD at lumbar spine (LS) and femoral neck (FN), serum osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) were assessed in 64 hypopituitaric patients (35 men, 30-50 yr) before and 2 yr after the beginning of GH replacement. Values of IGF-I and BMD at LS and at FN were expressed as Zscores. At study entry, IGF-I and BMD resulted similar among men and women with GHD. During GH replacement, IGF-I levels increased in both men and women without any difference in the percentage of IGF-I increase between the genders (p=0.47). In women receiving estrogen replacement, however, the percentage of IGF-I increase (p<0.05), and the Z IGF-I score (p<0.001) were significant lower than estrogen untreated women, although IGF-I levels were similar in the 2 groups (p=0.53). The GH dose adjusted for body weight required to restore normal age- and sex- matched IGF-I levels was lower in men than in women (p<0.001), and was higher in women receiving than in those not receiving estrogen replacement (p<0.05). In contrast, hypogonadal men treated with testosterone and eugonadal men received a similar GH dose (p=0.97). Also OC, Ntx levels, lumbar and femoral BMD improved (p<0.001) in all patients. Nevertheless, a greater increase in lumbar BMD increase was observed in men than in women (8.0+/-2.1 vs 2.6+/-0.4%; p<0.05). No significant difference was revealed in bone parameters in women treated or untreated with estrogen replacement and in men treated or not with testosterone replacement for concomitant hypogonadism. At the multiple correlation analysis, gender was a stronger predictor for the required GH dose than the age (p<0.001 and p=0.02, respectively). In conclusion, a 2-yr GH replacement normalizes IGF-I levels, increases bone mass and improves bone turnover both in men and in women with GHD without any difference between the 2 groups, provided that the dose of GH was modulated on the basis of IGF-I levels. Women receiving oral estrogens should receive a GH dose approximately doubled, as compared to men and women not receiving oral estrogens, to achieve similar effects on bone density and turnover. In particular, GH replacement dose, to be successful on bone mass and turnover, depends on gender in hypopituitary patients aged below 50 yr.

Both growth hormone (GH) and insulin-like growth factor I (IGF-I) are involved in heart development and in maintenance of cardiac structure and performance. Cardiovascular disease has been reported to reduce life expectancy in both GH deficiency (GHD) and GH excess. Patients with GHD suffer from a cluster of abnormalities associated with increased cardiovascular risk, including abnormal body composition, unfavorable lipid profile, increased fibrinogen and C-reactive protein levels, insulin resistance, early atherosclerosis and endothelial dysfunction, and impaired left ventricular (LV) performance (i.e., reduced diastolic filling and impaired response to peak exercise). Long-term GH replacement therapy reverses most of these abnormalities. More consistently, GH replacement reduces body fat and visceral adipose tissue, reduces low-density lipoprotein cholesterol and triglyceride levels, and improves endothelial function. GH replacement also reduces intima media thickness at major arteries and improves LV performance, but these results have been observed only in small series of patients treated on a short-term basis. This review discusses the roles of GHD and GH replacement therapy in the development of cardiovascular disease.

Morbidly obese subjects are characterized by multiple endocrine abnormalities and these are paralleled by unfavorable changes in body composition. In obese individuals, either 24-h spontaneous or stimulated GH secretion is impaired without an organic pituitary disease and the severity of the secretory defect is proportional to the degree of obesity. The GHRH+arginine (GHRH+ARG) test is likely to be the overall test of choice in clinical practice to differentiate GH deficiency (GHD) patients. Similarly to other provocative tests, GHRH+ARG is influenced by obesity per se. Therefore, a new cut-off limit of peak GH response of 4.2 microg/l in obese subjects has been recently assumed. The aim of the present study was to investigate the reciprocal influence between decreased GH secretion and body composition in a group of 110 morbidly obese subjects, using the new cut-off limit of peak GH response to GHRH+ARG test for these subjects. In our study, GHD was identified in 27.3% of the obese subjects, without gender difference. In GDH obese subjects body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), fat mass (FM), and resistance (R) were higher while reactance (Xc), phase angle, body cell mass (BCM), IGF-I, or IGF-I z-scores were lower than in normal responders (p<0.001). In all obese subjects, GH peak levels showed a negative correlation with age, BMI, waist circumference and FM, and a positive correlation with IGF-I. In the stepwise multiple linear regression, waist circumference and FM were the major determinants of GH peak levels and IGF-I. In conclusion, using the new cut-off limit of peak GH response to GHRH+ARG test for obese subjects, about 1/3 morbidly obese subjects were GHD. GHD subjects showed a significantly different body composition compared with normal responders, and the secretory defect was correlated to different anthropometric variables with waist circumference and FM as the major determinants.

To explore early effects of GH treatment or deprivation on cardiovascular risk factors and carotid intima-media thickness (IMT), we designed this randomized, cross-over study in 34 adult patients with severe GH deficiency. At study entry, the patients were randomized into two groups (A and B); group A (n = 17) received appropriate replacement therapy including GH at standard doses for 6 months and then were withdrawn from GH for the subsequent 6 months; group B (n = 17) received appropriate replacement therapy excluding GH for 6 months with the addition of GH in the subsequent 6 months. After the first 6 months, we observed a significant increase in IGF-I levels and of high-density lipoprotein (HDL)-cholesterol together with a significant decrease in diastolic blood pressure, the total/HDL-cholesterol ratio, and C-reactive protein in the patients in group A, whereas vascular parameters did not significantly change. In the patients in group B, none of the parameters studied significantly changed. After 6 months of GH withdrawal in the patients in group A, a significant decrease in IGF-I levels, a significant increase in the total/HDL-cholesterol ratio and C-reactive protein, and a trend toward an impairment of carotid IMT and peak velocities were observed. In the patients in group B, the addition of GH to the standard replacement induced a significant increase in IGF-I levels together with a decrease in systolic and diastolic blood pressure, total cholesterol and total/HDL-cholesterol ratio, and C-reactive protein, and an increase in HDL-cholesterol levels with a trend toward an improvement of vascular parameters. At the end of the study, mean IMT was significantly lower than at baseline both in group A (from 0.88 +/- 0.28 to 0.85 +/- 0.27 mm, P = 0.0003) and in group B (from 0.83 +/- 0.21 to 0.80 +/- 0.20 mm, P = 0.003). In conclusion, 6 months of GH replacement has beneficial effects whereas 6 months of GH deprivation has detrimental effects on cardiovascular risk factors and atherosclerosis. These findings support the indication for GH replacement in severe GH deficiency adult patients.

The physiological changes that the human body undergoes during aging are similar to those observed in GH deficiency (GHD). Early changes of aging are represented by increased fat mass, increased cardiovascular risk, reduced muscle mass and strength, reduced exercise tolerance, thinned skin, decreased strength and impaired quality of life. These observations led to hypothesize that the elderly could be GH deficient and would benefit from GH treatment. However, the effects of GH treatment in healthy elderly subjects by randomized and controlled studies are less promising than initially hypothesized. The etiopathology of age-related bone loss is multifactorial including menopause, andropause, somatopause and secondary hyperparathyroidism. GH has multiple effects on bone, either direct or mediated by IGF-I, stimulating osteoblast proliferation as well as osteoclast differentiation. Consequently, decline in GH secretion reduces bone turnover that causes osteopenia in young adults, but it has been hypothesized that it could protect against fractures in elderly subjects. The increase of bone remodeling achieved by GH therapy may be helpful in elderly men and women who have severely decreased bone turnover and impaired osteoblastic function. In conclusion, the endocrine pattern of aging is distinct from the decrease of GH/IGF-I levels associated with hypopituitarism. However, GH plays a role in metabolism and bone physiology throughout the human life span, although there is insufficient evidence for a clear therapeutic role of rhGH in aging. Thus, more data are needed to define the effects of somatopause to identify who could potentially benefit from the effects of somatotropic treatment.