Abstract-In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study.Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04 -12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; PϽ0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls. (Hypertension. 2012;60:618-624.) • Online Data Supplement Key Words: Conn syndrome Ⅲ aldosterone Ⅲ renin Ⅲ cardiovascular Ⅲ morbidity Ⅲ mortality A ldosterone is a key regulator of fluid and electrolyte balance in human physiology. Aldosterone excess in the presence of a high-sodium diet raises blood pressure. High blood pressure, together with direct proinflammatory and profibrotic effects of aldosterone on the vessel wall, causes and sustains cardiovascular atherosclerosis. 1,2 In keeping with these findings, high aldosterone levels are associated with mortality in heart failure cohorts, 3 and blockade of the renin-angiotensin-aldosterone system by mineralocorticoid antagonists improves outcome in heart failure and after myocardial infarction. 4,5 The contribution of aldosterone to the development of arterial hypertension in the general population has been suggested by the Framingham Offspring Study, in which plasma aldosterone levels in normotensive subjects predicted subsequent increases in blood pressure and the development of hypertension. 6 Recent evidence suggests that primary aldosteronism (PA) is more common than previously thought. 7 Several studies have provided evidence that patients with PA are especially prone to cardiovascular and renal complications. In a recent study by Catena et al, 8 aldosterone excess caused left ventricular hypertrophy and diastolic dysfunction independent of blood pressu...

Abstract-Primary aldosteronism is the most frequent cause of endocrine hypertension. Three forms of familial hyperaldosteronism (FH) have been described, named FH-I to -III. Recently, a mutation of KCNJ5 has been shown to be associated with FH-III, whereas the cause of FH-II is still unknown. In this study we searched for mutations in KCNJ5 in 46 patients from 21 families with FH, in which FH-I was excluded. We identified a new germline G151E mutation in 2 primary aldosteronism-affected subjects from an Italian family and 3 somatic mutations in aldosterone-producing adenomas, T158A described previously as a germline mutation associated with FH-III, and G151R and L168R both described as somatic mutations in aldosterone-producing adenoma. The phenotype of the family with the G151E mutation was remarkably milder compared with the previously described American family, in terms of both clinical and biochemical parameters. Furthermore, patients with somatic KCNJ5 mutations displayed a phenotype indistinguishable from that of sporadic primary aldosteronism. The functional characterization of the effects of the G151E mutation in vitro showed a profound alteration of the channel function, with loss of K ϩ selectivity, Na ϩ influx, and membrane depolarization. These alterations have been postulated to be responsible for voltage gate Ca 2ϩ channel activation, increase in cytosolic calcium, and stimulation of aldosterone production and adrenal cell proliferation. In conclusion, we describe herein a new mutation in the KCNJ5 potassium channel associated with FH-III, responsible for marked alterations of channel function but associated with a mild clinical and hormonal phenotype. (Hypertension. 2012;59: 235-240.) • Online Data Supplement Key Words: familial hyperaldosteronism Ⅲ endocrine hypertension Ⅲ primary aldosteronism Ⅲ aldosterone Ⅲ KCNJ5 P rimary aldosteronism (PA) is the most frequent cause of secondary hypertension, and its prevalence increases with blood pressure severity. 1 PA diagnosis is of paramount importance for the patient, not only because specific therapy is available, mineralocorticoid receptor antagonists for bilateral forms and adrenalectomy for unilateral forms, 2 but also because aldosterone causes detrimental effects on the cardiovascular system that are at least partly independent of blood pressure levels. 3,4 Current guidelines of the Endocrine Society recommend the confirmation or exclusion of PA in all groups of patients with an increased risk of the disease, 1 which include hypertensive patients with a family history of early onset hypertension or cerebrovascular events at a young age and all hypertensive first-degree relatives of patients with PA. These indications recognize the importance of testing for PA in patients at risk for familial hyperaldosteronism (FH). Three forms of FH have been described to date, named FH-I to -III. 5-8 FH-I, also known as glucocorticoid-remediable aldosteronism (GRA), is attributed to a chimeric CYP11B1/ CYP11B2 gene encoding a hybrid enzyme able to synthesize al...

Persistent postoperative hypoaldosteronism with hyperkalemia occurs in 5% of adrenalectomized PA patients through prolonged ZG insufficiency, requiring long-term fludrocortisone treatment. Potassium levels after adrenalectomy must be monitored to avoid life-threatening hyperkalemia.

Aldosterone excess has a direct negative effect on β-cell function in patients with PA. After adrenalectomy, glucose-induced first-phase insulin secretion improves significantly in the patients.

Objective: Adrenal vein sampling (AVS) is considered the gold standard in the differential diagnosis of primary aldosteronism (PA), but success rates vary between centers. We hypothesized that rapid (intraprocedure) cortisol measurement can improve performance in a center with initially low AVS success rate. Design: We analyzed 46 patients with confirmed PA studied between 2008 and 2010. Forty-seven PA patients studied between 2004 and 2008 identified by retrospective chart review served as controls. All patients were treated at a single tertiary care university hospital. Methods: Starting in 2008, rapid cortisol assays (RCA) were performed in all patients during the AVS procedure. A cortisol gradient of R2.0 between adrenal vein and a femoral vein sample was used as success criterion. Up to two repeat samples were drawn if adrenal vein cortisol was below this threshold. Results: During the control period 26 of 47 AVS were successful (55%). After introduction of RCA, 39 out of 46 AVS (85%) were successful (PZ0.003). In 21 of the 46 cases (46%) a resampling was necessary. The increase in overall success was due to an increase in successful right AVS (85 vs 62% before introduction of RCA; PZ0.02) and a training effect (PZ0.024 for trend). Conclusion: RCA during AVS are useful in centers with an initially low AVS success rate.

This study supports the RAAS to be involved in the pathogenesis of depression as patients with PA seem to be more depressive and anxious compared to the normal population. Gender differences in the regulation of the RAAS seem to be apparent, as females were more affected by the dysregulation than males.

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