The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Growth hormone nadir during oral glucose load depends on waist circumference, gender and age: normative data in 231 healthy subjects.

Objective  (i) To analyse the predictors of GH suppression after standard glucose load (oGTT) in the healthy population and (ii) to establish the 97th percentile of GH nadir post-oGTT according to these variables. Design  Analytical, retrospective. Measurements  GH nadir after oGTT. Subjects  Two hundred and thirty-one healthy subjects (113 women, 118 men 15-80 years) were studied. Results  The GH nadir after glucose load ranged from 0·01 (<assay detection limit) to 0·65 μg/l was higher in women and was inversely correlated with age, BMI, waist circumference, waist/hip, total cholesterol, triglycerides, basal and maximal glucose and basal insulin levels and directly correlated with basal GH levels, IGF-I SDS and HDL-cholesterol (P values ranging 0·004-<0·0001). On multistep regression analysis, the best predictors of nadir GH levels were waist circumference (t = -9·64, P < 0·0001), gender (t = -3·86, P = 0·0001) and age (t = -3·63, P = 0·0003). The results of comparative analysis among subjects grouped according to these variable showed different results in GH nadir in premenopausal women with waist circumference ≤88 cm (97th percentile 0·65 μg/l), in premenopausal women with waist circumference ≤88 cm and in men of any age with waist circumference ≤102 cm (97th percentile 0·33 μg/l) and in subjects of either gender and any age with waist circumference >88 cm in women and 102 cm in men (97th percentile 0·16 μg/l). Conclusions  The results of this study show that GH nadir after oGTT should be analysed according to gender, menopausal status and waist circumference. The GH cut-off should be limited to the assay used

Pasireotide Long-Acting Release Treatment for Diabetic Cats with Underlying Hypersomatotropism

BACKGROUND: Long‐term medical management of hypersomatotropism (HS) in cats has proved unrewarding. Pasireotide, a novel somatostatin analogue, decreases serum insulin‐like growth factor 1 (IGF‐1) and improves insulin sensitivity in cats with HS when administered as a short‐acting preparation. OBJECTIVES: Assess once‐monthly administration of long‐acting pasireotide (pasireotide LAR) for treatment of cats with HS. ANIMALS: Fourteen cats with HS, diagnosed based on diabetes mellitus, pituitary enlargement, and serum IGF‐1 > 1000 ng/mL. METHODS: Uncontrolled, prospective cohort study. Cats received pasireotide LAR (6–8 mg/kg SC) once monthly for 6 months. Fructosamine and IGF‐1 concentrations, and 12‐hour blood glucose curves (BGCs) were assessed at baseline and then monthly. Product of fructosamine concentration and insulin dose was calculated as an indicator of insulin resistance (Insulin Resistance Index). Linear mixed‐effects modeling assessed for significant change in fructosamine, IGF‐1, mean blood glucose (MBG) of BGCs, insulin dose (U/kg) and Insulin Resistance Index. RESULTS: Eight cats completed the trial. Three cats entered diabetic remission. Median IGF‐1 (baseline: 1962 ng/mL [range 1051–2000 ng/mL]; month 6: 1253 ng/mL [524–1987 ng/mL]; P < .001) and median Insulin Resistance Index (baseline: 812 μmolU/L kg [173–3565 μmolU/L kg]; month 6: 135 μmolU/L kg [0–443 μmolU/L kg]; P = .001) decreased significantly. No significant change was found in mean fructosamine (baseline: 494 ± 127 μmol/L; month 6: 319 ± 113.3 μmol/L; P = .07) or MBG (baseline: 347.7 ± 111.0 mg/dL; month 6: 319.5 ± 113.3 mg/dL; P = .11), despite a significant decrease in median insulin dose (baseline: 1.5 [0.4–5.2] U/kg; 6 months: 0.3 [0.0–1.4] U/kg; P < .001). Adverse events included diarrhea (n = 11), hypoglycemia (n = 5), and worsening polyphagia (n = 2). CONCLUSIONS AND CLINICAL IMPORTANCE: Pasireotide LAR is the first drug to show potential as a long‐term management option for cats with HS

Nutritional and Environmental Factors in Thyroid Carcinogenesis

Several epidemiological studies suggest an increased incidence of thyroid carcinoma (TC) in recent years, especially for the papillary histotype (PTC), suggesting that specific carcinogens might promote molecular abnormalities that are typical of PTC. The increased incidence is probably attributed to more intensive and sensitive diagnostic procedures, even if recent data suggest that various toxic elements could explain the phenomenon. Ionizing radiation exposure represents the most accepted risk factor for differentiated thyroid cancer that includes both the follicular and papillary histotypes. In this review, we examined the other environmental carcinogens that play a role in TC, such as eating habits, living in volcanic areas, and xenobiotic elements. Among eating habits, iodine intake represents one of the more discussed elements, because its deficiency is associated with follicular thyroid carcinomas (FTCs), while its progressive increment seems to be responsible for PTC. The gas, ash, and lava emissions of volcanoes are composed of various toxic compounds that pollute ground water, vegetables, and animals, contaminating humans via the food chain. Finally, the risk of developing PTC has also been associated with exposure of the population to xenobiotics in the environment or in the home. Their carcinogenic effects are probably caused by their accumulation, but additional studies are necessary to better understand the mechanisms of action

Pasireotide for the Medical Management of Feline Hypersomatotropism

BACKGROUND: Feline hypersomatotropism (HST) is a cause of diabetes mellitus in cats. Pasireotide is a novel multireceptor ligand somatostatin analog that improves biochemical control of humans with HST. HYPOTHESIS/OBJECTIVES: Pasireotide improves biochemical control of HST and diabetes mellitus in cats. ANIMALS: Hypersomatotropism was diagnosed in diabetic cats with serum insulin‐like growth factor‐1 (IGF‐1) concentration >1,000 ng/mL by radioimmunoassay and pituitary enlargement. METHODS: Insulin‐like growth factor 1 was measured and glycemic control assessed using a 12‐hour blood glucose curve on days 1 and 5. On days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF‐1, insulin dose, and estimated insulin sensitivity (product of the area under the blood glucose curve [BGC] and insulin dose) were compared pre‐ and post treatment. Paired t‐tests or Wilcoxon signed rank tests were employed for comparison where appropriate; a linear mixed model was created to compare BGC results. RESULTS: Insulin‐like growth factor 1 decreased in all 12 cats that completed the study (median [range] day 1: 2,000 ng/mL [1,051–2,000] and day 5: 1,105 ng/mL [380–1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5 than on day 1 (mean reduction 1.3 [0–2.7] units/kg/injection, P = .003, paired t‐test). The product of insulin dose and area under the BGC was lower on day 5 than day 1 (difference of means: 1,912; SD, 1523; u × mg/dL × hours, P = .001; paired t‐test). No clinically relevant adverse effects were encountered. CONCLUSIONS: Short‐acting pasireotide rapidly decreased IGF‐1 in cats with HST and insulin‐dependent diabetes. The decrease in IGF‐1 was associated with increased insulin sensitivity

Managing Cushing's disease: the state of the art.

Cushing's disease is a rare chronic disease caused by a pituitary adenoma, which leads to excess secretion of adrenocorticotropic hormone (ACTH). The over-production of ACTH leads to hyperstimulation of the adrenal glands and a chronic excess of cortisol, resulting in the signs and symptoms of a severe clinical state (Cushing's syndrome) that leads to significant morbidity, negative impacts on the patient's quality of life, and, if untreated, increased mortality. The management of patients with Cushing's disease is complicated by the heterogeneity of the condition, with signs and symptoms that overlap with those of other diseases, and high subclinical incidence rates. Controversies surrounding the tests used for screening and identifying patients with Cushing's disease add to the challenge of patient management. Surgical intervention to remove the adenoma is the first-line treatment for patients with Cushing's disease, but medical therapies are useful in patients who relapse or are unsuitable for surgery. The recent introduction of pasireotide, the first pituitary-directed medical therapy, expands the number of treatment options available for patients with Cushing's disease. This state-of-the-art review aims to provide an overview of the most recent scientific research and clinical information regarding Cushing's disease. Continuing research into improving the diagnosis and treatment of Cushing's disease will help to optimize patient management

Self-Assessment of Adherence to Medication: A Case Study in Campania Region Community-Dwelling Population.

Objectives. The aim of the study was to assess self-reported medication adherence measure in patients selected during a health education and health promotion focused event held in the Campania region. The study also assessed sociodemographic determinants of adherence. Methods. An interviewer assisted survey was conducted to assess adherence using the Italian version of the 8-item Morisky Medication Adherence Scale (MMAS-8). Participants older than 18 years were interviewed by pharmacists while waiting for free-medical checkup. Results. A total of 312 participants were interviewed during the Health Campus event. A total of 187 (59.9%) had low adherence to medications. Pearson's bivariate correlation showed positive association between the MMAS-8 score and gender, educational level and smoking (P &lt; 0.05). A multivariable analysis showed that the level of education and smoking were independent predictors of adherence. Individuals with an average level of education (odds ratio (OR), 2.21, 95% confidence interval (CI), 1.08-4.52) and nonsmoker (odds ratio (OR) 1.87, 95% confidence interval (CI), 1.04-3.35) were found to be more adherent to medication than those with a lower level of education and smoking. Conclusion. The analysis showed very low prescription adherence levels in the interviewed population. The level of education was a relevant predictor associated with that result

THE COMPLEX RELATIONSHIP BETWEEN OBESITY AND THE SOMATROPIC AXIS: THE LONG AND WINDING ROAD.

Despite the considerable body of evidence pointing to a possible relationship between state of the adipose tissue depots and regulation of the somatotropic axis, to date the relationship between obesity and low growth hormone (GH) status remains incompletely understood. The low GH status in obesity is mainly considered as a functional condition, largely reversible after a sustained weight loss. Moreover, due to the effects of the adiposity on the regulation of the somatotropic axis, the application of GH stimulation tests in obesity may also lead to an incorrect diagnosis of GH deficieny (GHD). On the other hand, similar to patients with GHD unrelated to obesity, the reduced GH response to stimulation testing in obese individuals is associated with increased prevalence of cardiovascular risk factors and detrimental alterations of body composition, which contribute to worsening their cardio-metabolic risk profile. In addition, the reduced GH secretion may result in reduced serum insulin-like growth factor (IGF)-1 levels, and the concordance of low peak GH and low IGF-1 identify a subset of obese individuals with high cardiovascular risk. Furthermore, after weight loss, the normalization of the GH response and IGF-1 levels may or may not occur, and in patients undergoing bariatric surgery the persistence of a low GH status may affect the post-operative outcomes. In this review, we will provide an overview on some clinically relevant aspects of the relationship between obesity axis and the somatotropic axis in the light of the recently published research

Obesogenic endocrine disruptors and obesity: myths and truths

Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products. The window of life during which the exposure happens could lead to different effects. A critical window is during utero and/or neonatal period in which the obesogens could cause subtle changes in gene expression and tissue organization or blunt other levels of biological organization leading to increased susceptibility to diseases in the adulthood. Some of the reasons for this increased sensitivity include the lack of the protective mechanisms that are available in adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism and the blood/brain barrier still not fully functional in the fetus or newborn. The mechanisms of action of obesogens lay on their ability to increase the number and/or the size of the adipocytes and to alter appetite, satiety and food preferences. The ability of obesogens to increase fat deposition results in an increased capacity for their own retention due to their lipophilic properties; thus prolonging the exposure and increasing the detrimental metabolic consequences