Sclerosing Angiomatoid Nodular Transformation of the Adrenal Gland: A Case Report of a Novel Histopathological Entity

The finding of an indeterminate adrenal mass at radiological investigations is a challenge for physicians. Complex diagnostic work-up, periodic follow-up, or surgical intervention are therefore needed to rule out malignant lesions. Tertiary care hospitals are provided with F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET) and F-18-dihydroxyphenylalanine (F-18-DOPA) PET, which aid in the characterization of indeterminate adrenal masses. Nevertheless, the histopathological examination may be required to exclude malignancy or rare etiologies. A 54-year-old woman presented to our clinic 6 months after a cerebral hemorrhage. She was hypertensive and had recently discovered a left adrenal mass of 15 mm during an abdominal ultrasound. Contrast-enhanced CT, following adrenal protocol, revealed a 14-mm adrenal mass without characteristics suggestive of an adrenal adenoma. Tumor markers were negative. Functional tests excluded hormone hypersecretion. An F-18-DOPA PET was negative. An F-18-FDG PET showed mild uptake of both the adrenal glands, with a more circumscribed pattern in the left one (maximum standardized uptake value 5 4). As the clinical diagnosis was still indeterminate, we performed laparoscopic left adrenalectomy. The histopathological examination described a sclerosing angiomatoid nodular transformation (SANT) of the adrenal gland, a benign lesion already described as a rare occurrence only in the spleen. IgG4 levels were reduced. In conclusion, this is a report of a SANT of the adrenal gland, a novel entity that should be taken into consideration in the differential diagnosis of indeterminate adrenal masses at CT scan. Copyright (C) 2019 Endocrine Societ

Body mass index rather than the phenotype impacts precocious ultrasound cardiovascular risk markers in polycystic ovary syndrome

Objective Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism. This study evaluates the most promising US CV risk markers in PCOS and compares them between different PCOS phenotypes and BMI values. Design Women fulfilling the Rotterdam criteria for PCOS were recruited from our outpatient clinic for this cross-sectional study. Methods Participants (n\u2009=\u2009102) aged 38.9 \ub1 7.4 years were stratified into the four PCOS phenotypes and the three BMI classes (normal-weight, overweight, obese). They were assessed for clinical and biochemical parameters together with the following US markers: coronary intima-media thickness (cIMT), flow-mediated vascular dilation (FMD), nitroglycerine-induced dilation (NTG), and epicardial fat thickness (EFT). Results There was no statistical difference among the four phenotypes in terms of cIMT, FMD, NTG or EFT, however all the US parameters except NTG showed significant differences among the three BMI classes. Adjusting for confounding factors in multiple regression analyses, EFT retained the greatest direct correlation with BMI and cIMT remained directly correlated but to a lesser degree. Conclusions This study showed that obesity rather than the hyperandrogenic phenotype negatively impacts precocious US CV risk markers in PCOS. In addition, EFT showed the strongest association with BMI, highlighting its potential for estimating CV risk in PCOS

Il sistema endocannabinoide e il controllo del metabolismo energetico: fisiologia e fisiopatologia

The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system has recently been shown to control several metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, therefore drugs interfering with this overactivation by blocking CB1 receptor are considered as valuable candidates for the treatment of obesity and related cardiometabolic risk factors. \ua9 2008 AIM Publishing Srl

Metabolic consequences: Obesity and energy expenditure, can they be treated?

Obesity and hypopituitarism are major side effects of craniopharyngiomas. Awareness of the presence of obesity and/or food-seeking behavior in patients affected by acquired pathologic processes damaging the hypothalamic centers is highly recommended. The craniopharyngiomas cause structural damage to the hypothalamus before or, more often, after surgery. These tumors may occur at any age but are more common in childhood and adolescence. Obesity may often appear before any therapeutic approach is attempted. Obesity and hyperphagia as a consequence of surgical or radiotherapy treatment must be managed with particular care. This chapter will try to highlight the potential medical and surgical treatments to limit obesity, hyperphagia, and alterations in energy expenditure often described in patients affected by craniopharyngioma, elucidating at the same time the mechanisms by which all these metabolic alterations may occur

La terapia farmacologica dell'obesità

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by partially blocking the hydrolysis of dietary triglycerides. A recent meta-analysis evaluated 22 studies lasting for at least 12 months, in obese patients with a mean body mass index of 36.7 kg/m2, where orlistat was associated with hypocaloric diet or behavioral interventions: the net average weight loss was 2.89 kg (confidence interval 2.27-3.51 kg). Considering the principal studies, attrition rate ranged from 33 to 57%. Orlistat significantly decreases waist circumference, blood pressure, total and LDL cholesterol, but has no effect on HDL and triglycerides. This drug significantly reduced the incidence of diabetes only in subjects with impaired glucose tolerance. The major adverse effects with orlistat are mainly gastrointestinal (fatty and oily stool, fecal urgency, oily spotting, fecal incontinence) and attenuate over time. Orlistat should be avoided in patients with chronic malabsorption and cholestasis. Rimonabant is a selective antagonist of cannabinoid type 1 receptor. This drug, by inhibiting the overactivation of the endocannabinoid system, produces anorectic stimuli at the central nervous level, but also has effects on the peripheral systems involved in metabolism control, such as liver, adipose tissue, skeletal muscles, endocrine pancreas, and gastrointestinal apparatus, influencing many processes partially unknown. An ample experimental program named RIO (Rimonabant In Obesity) involved about 6600 obese or overweight patients to identify the effects of rimonabant in weight loss and associated cardiometabolic abnormalities, over and beyond a caloric restriction of 600 kcal in the treatment and placebo arms. In the four double-blind RIO trials published (Rio-North America, RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant 20 mg significantly (p < 0.001) reduced weight by 6.3-6.9 kg in the non-diabetic groups vs placebo (-1.5-1.8 kg), whereas in the diabetic subjects enrolled in RIO-Diabetes, weight loss was 5.3 vs 1.4 kg in the placebo group. Attrition rate at 1 year ranged between 40 and 50%, similar to the studies with sibutramine or orlistat. Similarly to weight loss, also waist circumference was significantly reduced by rimonabant. As for cardiometabolic parameters, rimonabant induced a significant increase in HDL cholesterol and a significant decrease in triglycerides. Even if no significant LDL reduction was achieved, the RIO-Lipids study showed a significant decrease in small dense LDL particles, more atherogenic, in rimonabant-treated subjects. Non-diabetic treated patients improved basal insulin and indirect indexes of insulin resistance, while in the RIO-Diabetes study, the only one including diabetics, glycated hemoglobin improved by 0.7% in the active treatment arm vs placebo. The effects on HDL cholesterol and glycated hemoglobin seem in a large percentage unrelated to weight loss. These effects have been confirmed by another trial, named SERENADE, evaluating the treatment in naive diabetic patients. Rimonabant is not recommended in patients with a history of depressive disorders or suicidal ideation and with uncontrolled psychiatric illness, and is contraindicated in patients with ongoing major depression or ongoing antidepressive treatment. In conclusion, despite an enormous advancement in basic research to understand the pathogenetic mechanisms at the base of obesity, the pharmacological research did not reach the therapeutic opportunities available for other chronic conditions, like hypertension and dyslipidemia. However, the few molecules available for clinical practice (sibutramine, orlistat, rimonabant) have shown, when properly used, to contribute to reduce body weight and undoubtedly improve cardiometabolic risk factors. With this preamble, according to current guidelines and pharmacoeconomic studies, patients who might benefit from antiobesity treatment are those with a body mass index ≥ 30 or 27-29.9 kg/m2 with major obesity-related comorbidities such as hypertension, diabetes, dyslipidemia, obstructive sleep apnea, and metabolic syndrome. © 2008 AIM Publishing Srl

Glucocorticoids and Type 2 Diabetes: From Physiology to Pathology

Type 2 diabetes mellitus is the result of interaction between genetic and environmental factors, leading to heterogeneous and progressive pancreatic β-cell dysfunction. Overweight and obesity are major contributors to the development of insulin resistance and impaired glucose tolerance. The inability of β cells to secrete enough insulin produces type 2 diabetes. Abnormalities in other hormones such as reduced secretion of the incretin glucagon-like peptide 1 (GLP-1), hyperglucagonemia, and raised concentrations of other counterregulatory hormones also contribute to insulin resistance, reduced insulin secretion, and hyperglycaemia in type 2 diabetes. Clinical-overt and experimental cortisol excess is associated with profound metabolic disturbances of intermediate metabolism resulting in abdominal obesity, insulin resistance, and low HDL-cholesterol levels, which can lead to diabetes. It was therefore suggested that subtle abnormalities in cortisol secretion and action are one of the missing links between insulin resistance and other features of the metabolic syndrome. The aim of this paper is to address the role of glucocorticoids on glucose homeostasis and to explain the relationship between hypercortisolism and type 2 diabetes

The unrelenting fall of the pharmacological treatment of obesity

Nowadays pharmacological therapy to limit obesity has reached a critical stage: not only have Authorities limited the use of antiobesity drugs due to their proven inefficacy and dangerous side effects, but bariatric surgery has delivered better results. At present, when the number of obese subjects is growing exponentially worldwide and more and more pathological mechanisms inducing fat accumulation have been discovered, no drugs are available to help patients and physicians to limit one the most dreadful causes of death. Following the failures of promising drugs as sibutramine and rimonabant, many companies stopped to invest in the field of obesity pharmacotherapy. At the same time, leading Authorities have started to require more solid evidence before providing authorization for these drugs to enter the market. This review aims at revising the failed promises of antiobesity drugs and describing the few potential future candidates in order to shed some light in the still uncertain field of antiobesity drugs. It also provides a critical contribution to the ongoing debate among scientists, clinicians, patients and Authorities on the possibility to treat obesity with pharmacological drugs