Maria Cristina Savanelli

Growth Hormone Treatment on Atherosclerosis : Results of a 5-Year Open, Prospective, Controlled Study in Male Patients with Severe Growth Hormone Deficiency

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.

Nutrition and psoriasis: is there any association between the severity of the disease and adherence to the Mediterranean diet?

BackgroundMany 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.MethodsThis 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.ResultsA 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, (r2=0.537, β=0.740, p<0.001), and FM (r2=0.537, β=0.603, p<0.001) and PREDIMED score (r2=0.599, β=−0.296, p=0.007) among anthropometric measures, FM and PREDIMED score. Finally, among all items of the PREDIMED questionnaire, EVOO (r2=0.548, β=−0.741, p<0.001), and fish consumption (r2=0.139, β=−0.372, p=0.005) have an independent predictive value for PASI score and CRP levels.ConclusionsThis 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.

The cardiovascular system in growth hormone excess and growth hormone deficiency.

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.

GH and IGF‐I deficiency are associated with reduced loss of fat mass after laparoscopic‐adjustable silicone gastric banding

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.

Vitamin D and its role in psoriasis: An overview of the dermatologist and nutritionist

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.

Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender

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 Z-scores. 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.

Environmental Risk Factors in Psoriasis: The Point of View of the Nutritionist

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.

Endocrine Aspects of Environmental “Obesogen” Pollutants

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.

Low vitamin D status and obesity: Role of nutritionist

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 D3 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 D3 receptors and enzymes responsible for vitamin D3 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.

Role of pituitary dysfunction on cardiovascular risk in primary empty sella patients

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.