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.

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.

No abstract

We investigated the natural course of adrenal incidentalomas in 115 patients by means of a long-term endocrine and morphological (CT) follow-up protocol (median 4 year, range 1 -7 year). At entry, we observed 61 subclinical hormonal alterations in 43 patients (mainly concerning the ACTH -cortisol axis), but confirmatory tests always excluded specific endocrine diseases. In all cases radiologic signs of benignity were present. Mean values of the hormones examined at last follow-up did not differ from those recorded at entry. However in individual patients several variations were observed. In particular, 57 endocrine alterations found in 43 patients (37.2%) were no longer confirmed at follow-up, while 35 new alterations in 31 patients (26.9%) appeared de novo. Only four alterations in three patients (2.6%) persisted. Confirmatory tests were always negative for specific endocrine diseases. No variation in mean mass size was found between values at entry (25.470.9 mm) and at follow-up (25.770.9 mm), although in 32 patients (27.8%) mass size actually increased, while in 24 patients (20.8%) it decreased. In no case were the variations in mass dimension associated with the appearance of radiological criteria of malignancy. Kaplan -Meier curves indicated that the cumulative risk for mass enlargement (65%) and for developing endocrine abnormalities (57%) over time was progressive up to 80 months and independent of haemodynamic and humoral basal characteristics. In conclusion, mass enlargement and the presence or occurrence over time of subclinical endocrine alterations are frequent and not correlated, can appear at any time, are not associated with any basal predictor and, finally, are not necessarily indicative of malignant transformation or of progression toward overt disease.

Objective: To compare clinical and humoral parameters before and after surgery in patients with incidental adrenocortical adenomas. Design: Six patients with subclinical Cushing's syndrome and nine with non-functioning adenomas were investigated before and 12 months after removal of the mass. Methods: Anthropometric (body weight, body mass index and waist to hip ratio), haemodynamic (blood pressure and heart rate), metabolic (lipids and oral glucose tolerance test (OGTT)), hormonal (cortisol, plasma renin activity, aldosterone, androgens and catecholamines) and bone metabolism (hydroxyproline, parathyroid hormone, osteocalcin and ostase) parameters were evaluated. Results: In the whole group, a significant decrease in body weight ð69:7^3:5 vs 70:8^3:5 kg; P , 0:03Þ; in systolic ð135:3^5:1 vs 145:6^4:9 mmHg; P , 0:009Þ and diastolic ð83:7^1:9 vs 91:0^3:5 mmHg; P , 0:03Þ blood pressure and in glucose levels in response to OGTT ð106:4^9:6 vs 127:5^6:5 mg=dl; P , 0:05Þ was observed after surgery. All other parameters examined did not change significantly. This trend was also found in both groups separately. Analytical data showed a high frequency of overweight/obesity (66.6%), hypertension (66.6%) and impaired glucose profile (26.6%) in our patients, with a greater prevalence of these cardiovascular risk factors in the subclinical Cushing's syndrome group. After surgery, values normalized or improved in eight out of ten hypertensive patients and in three out of four patients with impaired glucose profile. Conclusions: Solid adrenocortical incidentalomas are associated with some cardiovascular risk factors which may be corrected after removal of the mass. Therefore, surgery may be an appropriate choice in patients with subclinical Cushing's syndrome but also in those with solid non-functioning adenomas and coexistent cardiovascular risk factors.

The effects of interferon-alpha (IFN-alpha) on clinical and serologic manifestations of mixed cryoglobulinemia (MC) were investigated by randomized, crossover-controlled trial in 26 patients. The trial alternated 6 months with and 6 months without IFN-alpha therapy (2 x 10(6) IU daily for a month, then every other day for 5 months). In 22 patients, pretreatment steroid dosage remained unchanged during the study. Six patients dropped out (three because of side effects), whereas another 20 patients experienced a significant improvement of purpura (P < .02) and serum transaminases (P < .005) during IFN-alpha treatment. The presence of clinical improvement was supported by the outcome measurements of several immunologic parameters. In particular, serum cryoglobulins were significantly reduced (P < .04) during IFN- alpha therapy. A rebound phenomenon of clinical and serologic parameters was observed after IFN-alpha discontinuation. In addition, no variations were recorded during 6 months without therapy. Hepatitis C virus (HCV) RNA was detected in 91% (20/22) of our MC patients; in 2/13 cases HCV RNA was no longer detectable in serum samples after IFN- alpha therapy. Thus, IFN-alpha could be considered as treatment for MC in patients with HCV seropositivity.

The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P < 0.03-0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P < 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P < 0.02), while A was negatively associated with body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.

EMANUELE MARZO, PIER VITTORIO FOSELLA, GIAMPIERO PASERO. and STEFAN0 BOMBARDIER1The prevalence of antibodies to hepatitis C virus (HCVAb) was investigated in 52 unselected patients with mixed cryoglobulinemia and in 84 patients with other systemic immunologic diseases. HCVAb were detected by an enzyme-linked immunosorbent assay, and their specificity was evaluated by a recombinant-based immunoblot assay. The presence of HBV-related markers was investigated in the same samples. HCVAb were found in 54% of mixed cryoglobulinemia patients, and the finding was confirmed by recombinant-based immunoblot assay in all cases. HCVAb and/or HBV markers were present in 70% of the patients. HCVAb seropositivity was significantly more frequent in mixed cryoglobulinemia patients with biopsy-proven liver involvement (P < 0.01) and with increased serum transaminase levels (P < 0.01). HCVAb were virtually absent in control patients with other immunologic diseases. These results support the notion that viral agents, i.e., HCV and possibly HBV, have a role in the pathogenesis of mixed cryoglobulinemia patients.