In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.

Abstract-Primary aldosteronism (PA) has been associated with cardiovascular hypertrophy and fibrosis, in part independent of the blood pressure level, but deleterious effects on the kidneys are less clear. Likewise, it remains unknown if the kidney can be diversely involved in PA caused by aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Hence, in the Primary Aldosteronism Prevalence in Italy (PAPY) Study, a prospective survey of newly diagnosed consecutive patients referred to hypertension centers nationwide, we sought signs of renal damage in patients with PA and in comparable patients with primary hypertension (PH). Patients (nϭ1180) underwent a predefined screening protocol followed by tests for confirming PA and identifying the underlying adrenocortical pathology. Renal damage was assessed by 24-hour urine albumin excretion (UAE) rate and glomerular filtration rate (GFR). UAE rate was measured in 490 patients; all had a normal GFR. Of them, 31 (6.4%) had APA, 33 (6.7%) had IHA, and the rest (86.9%) had PH. UAE rate was predicted (PϽ0.001) by body mass index, age, urinary Na ϩ excretion, serum K ϩ , and mean blood pressure. Covariate-adjusted UAE rate was significantly higher in APA and IHA than in PH patients; there were more patients with microalbuminuria in the APA and IHA than in the PH group (Pϭ0.007). Among the hypertensive patients with a preserved GFR, those with APA or IHA have a higher UAE rate than comparable PH patients. Thus, hypertension because of excess autonomous aldosterone secretion features an early and more prominent renal damage than PH. Key Words: hypertension, endocrine Ⅲ aldosterone Ⅲ mineralocorticoids Ⅲ kidney Ⅲ hypertrophy Ⅲ adrenal gland T he results of large intervention trials 1,2 and cross-sectional studies (reviewed by Rossi et al 3 ) have recently refueled the interest on the deleterious cardiovascular effects of excess aldosterone. Moreover, growing evidence 4 indicates that primary aldosteronism (PA) is a common cause of secondary hypertension: in the Primary Aldosteronism Prevalence in Italy (PAPY) study, a prospective survey of 1180 consecutive newly diagnosed hypertensive patients referred to specialized hypertension centers, aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were found in 4.8% and 6.4% of all patients, respectively, thus leading to an overall prevalence of PA of Ϸ11%. 5 It has been contended that this form of secondary hypertension is relatively "benign," that is, devoid of cardiovascular complications, because of the suppression of the renin-angiotensin system, which plays a substantial role in cardiovascular remodeling and damage. 6,7 This view has, however, been challenged by recent data. 3,8 PA has in fact been associated with widespread tissue fibrosis, 9 vascular remodeling, 10 and excess prevalence of left ventricular hypertrophy and diastolic dysfunction 11 that were corrected by adrenalectomy. 12 A higher incidence of cardiovascular complications, including atrial fibrillation, has also been...

Objective. Benign thyroid nodules are a common occurrence whose only remedy, in case of symptoms, has always been surgery until the advent of new techniques, such as radiofrequency ablation (RFA). This study aimed at evaluating RFA efficacy, tolerability, and costs and comparing them to hemithyroidectomy for the treatment of benign thyroid nodules. Design and Methods. 37 patients who underwent RFA were retrospectively compared to 74 patients surgically treated, either in a standard inpatient or in a short-stay surgical regimen. Efficacy, tolerability, and costs were compared. The contribution of final pathology was also taken into account. Results. RFA reduced nodular volume by 70% after 12 months and it was an effective method for treating nodule-related clinical problems, but it was not as effective as surgery for the treatment of hot nodules. RFA and surgery were both safe, although RFA had less complications and pain was rare. RFA costed €1,661.50, surgery costed €4,556.30, and short-stay surgery costed €4,139.40 per patient. RFA, however, did not allow for any pathologic analysis of the nodules, which, in 6 patients who had undergone surgery (8%), revealed that the nodules harboured malignant cells. Conclusions. RFA might transform our approach to benign thyroid nodules.

Background-Although in vitro studies have suggested that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might be involved in vascular biology, its potential role in the pathogenesis and/or treatment of atherosclerosis has not been investigated. Methods and Results-Both recombinant human TRAIL and an adeno-associated virus vector expressing human TRAIL were used to deliver TRAIL in apolipoprotein E (apoE)-null mice in which diabetes mellitus was induced by destruction of islet cells with streptozotocin. Diabetes in apoE-null mice was associated with a significant increase in atherosclerotic plaque area and complexity in the aorta as assessed by a marked increase in interstitial collagen, cellular proliferation, and macrophage infiltration and a focal loss of endothelial coverage. Repeated intraperitoneal injections of recombinant human TRAIL and a single intravenous injection of adeno-associated virus-human TRAIL significantly attenuated the development of atherosclerotic plaques in apoE-null animals. TRAIL also markedly affected the cellular composition of plaque lesions by inducing apoptosis of infiltrating macrophages and increasing the vascular smooth muscle cell content. Moreover, TRAIL promoted the in vitro migration of cultured human aortic vascular smooth muscle cells but not of monocytes or macrophages. Conversely, TRAIL selectively induced apoptosis of human cultured macrophages but not of vascular smooth muscle cells. Conclusions-Overall, data from the present study indicate that atherosclerosis in diabetic apoE-null mice is ameliorated by systemic TRAIL administration and that adeno-associated virus-mediated TRAIL gene delivery might represent an innovative method for the therapy of diabetic vascular diseases.

BMI correlated with PAC independent of age, sex, and sodium intake in PH, but not in PA patients. This association of BMI is particularly evident in overweight-obese PH patients, and suggests a pathophysiological link between visceral adiposity and aldosterone secretion. However, it does not impact on the diagnostic accuracy of the ARR for discriminating PA from PH patients.

Serum osteoprotegerin (OPG) is significantly increased in diabetic patients, prompting expanded investigation of the correlation between OPG production/release and glycemic levels. Serum levels of OPG, but not of its cognate ligand receptor activator of nuclear factor-B ligand (RANKL), were significantly increased in type 2 diabetes mellitus patients compared with healthy blood donors. Serum OPG was also significantly elevated in a subgroup of recently diagnosed diabetic patients (within 2 years). The relationship between serum OPG and diabetes mellitus onset was next investigated in apoE-null and littermate mice. Serum OPG increased early after diabetes induction in both mouse strains and showed a positive correlation with blood glucose levels and an inverse correlation with the levels of free (OPG-unbound) RANKL. The in vitro addition of tumor necrosis factor-␣ to human vascular endothelial cells, but not human peripheral blood mononuclear cells, markedly enhanced OPG release in culture. In contrast, high glucose concentrations did not modulate OPG release when used alone or in association with tumor necrosis factor-␣. Moreover, the ability of soluble RANKL to activate the extracellular signal-regulated kinase/mitogen-activated protein kinase and endothelial nitric-oxide synthase pathways in endothelial cells was neutralized by preincubation with recombinant OPG. Altogether, these findings suggest that increased OPG production represents an early Receptor activator of nuclear factor (NF)-B ligand (RANKL) is a member of the tumor necrosis factor (TNF) family of cytokines, which exists either as type II membrane or as soluble protein.1 RANKL was originally described as being expressed by activated T lymphocytes and osteoblasts, and it has been involved in the interaction between T lymphocytes and dendritic cells, osteoclast differentiation from monocytic precursor cells, and activation of mature osteoclasts.1-6 Two receptors for RANKL have been identified: transmembrane RANK and soluble osteoprotegerin (OPG).2,3,5 RANK mRNA is ubiquitously expressed in human tissues, but RANK protein expression has been characterized only in normal dendritic cells, CD4 and CD8 T lymphocytes, osteoclast monocytic precursors, and endothelial cells, suggesting that expression of this protein is posttranscriptionally regulated. 6 For the purpose of this study, it is noteworthy that, by interacting with RANK, RANKL induces a variety of biological effects on endothelial cells, such as promotion of cell survival and angiogenesis. [7][8][9] Although the affinity of RANKL for OPG is weaker than that for RANK,5 when present at high concentrations soluble OPG prevents RANKL interaction with transmembrane RANK, thus acting as a decoy receptor. 3,5 It has been shown that OPG is produced by a wide range of tissues, including the cardiovascular system, and that OPG levels are particularly high in aortic and renal arteries. 10 -12 Interestingly, different groups of investigators have reported that serum OPG is significantly increased in both t...

Primary aldosteronism (PA) causes cardiovascular damage in excess to the blood pressure elevation, but there are no prospective studies proving a worse long-term prognosis in adrenalectomized and medically treated patients. We have, therefore, assessed the outcome of PA patients according to treatment mode in the PAPY study (Primary Aldosteronism Prevalence in Hypertension) patients, 88.8% of whom were optimally treated patients with primary (essential) hypertension (PH), and the rest had PA and were assigned to medical therapy (6.4%) or adrenalectomy (4.8%). Total mortality was the primary end point; secondary end points were cardiovascular death, major adverse cardiovascular events, including atrial fibrillation, and total cardiovascular events. Kaplan-Meier and Cox analysis were used to compare survival between PA and its subtypes and PH patients. After a median of 11.8 years, complete follow-up data were obtained in 89% of the 1125 patients in the original cohort. Only a trend (=0.07) toward a worse death-free survival in PA than in PH patients was observed. However, at both univariate (90.0% versus 97.8%; =0.002) and multivariate analyses (hazard ratio, 1.82; 95% confidence interval, 1.08-3.08;=0.025), medically treated PA patients showed a lower atrial fibrillation-free survival than PH patients. By showing that during a long-term follow-up adrenalectomized aldosterone-producing adenoma patients have a similar long-term outcome of optimally treated PH patients, whereas, at variance, medically treated PA patients remain at a higher risk of atrial fibrillation, this large prospective study emphasizes the importance of an early identification of PA patients who need adrenalectomy as a key measure to prevent incident atrial fibrillation.

This study shows that a single radiofrequency ablation was effective in 50 % of patients with autonomously functioning benign thyroid nodules. Patients responded gradually to the treatment. It is possible that longer follow-up studies might show greater response rates.