JNEPHROL 2008; 21: 447-454 THOROUGH CRITICAL APPRAISAL 447 ABSTRACT Over the last few years compelling evidence has been gathered to support the view that primary aldosteronism (PA) is far more prevalent than usually held: its preva- lence rate among consecutive newly diagnosed hyper- tensive patients referred to hypertension centers can be as high as 11.2%. Moreover, about 4.8% of cases are a surgically curable endocrine form of hypertension, and the majority of cases do not exhibit hypokalemia at the time of clinical presentation. The impact of these results on the strategy to be used in the clinical investigation of patients with hypertension is discussed in light of novel information on the optimal screening strategy to be used for pinpointing the PA patients from the vast array of hy- pertensive patients. Key words: Aldosterone, Hypertension, Primary aldos- teronism, Renal damage, Renin INTRODUCTION The pathophysiology of the adrenal gland remained unde- fined until 1948 when Deane found that the mineralocorticoid electrocortin, thereafter renamed aldosterone, was produced in the adrenal cortex (for a review of history of aldosterone, see (1)). In 1955, Dr. Jerome W. Conn described for the first time, and before aldosterone was known, primary aldostero- nism (PA), in a woman with an adrenocortical tumor who was cured with adrenalectomy (2, 3). Ten years later he contended that PA was quite common even in the absence of hypokalemia, one of the hallmarks of the disease, because more than 20% of the hypertensive patients he had screened were eventually found to have PA (4-6). However, as others could not confirm this experience, most continued to believe that PA was extremely rare. Even though Conn eventually admitted that a more realistic estimate of the prevalence of PA was 7.5% (7), estimates of PA prevalence were subse- quently reported over an enormous range, from 1.4% to 32% (median 8.8%), most likely because of differences across the studies, which were almost uniformly performed retrospec- tively in selected cohorts (for review, see (8)). Nevertheless, many experts perceived that PA could be far more prevalent than was usually held (9-26). In 2006, a large prospective sur- vey of consecutive newly diagnosed hypertensive patients referred to hypertension centers nationwide in Italy, the PA Prevalence in Hypertensives (PAPY) study eventually provid- ed conclusive evidence to support this view. In this study, after a screening test based on the plasma aldosterone con- centration (PAC) to plasma renin activity (PRA) ratio (known as the aldosterone renin ratio [ARR]) at baseline and after captopril, the patients underwent a comprehensive diagnostic work-up that allowed the presence or absence of PA to be Gian Paolo Rossi, Teresa Maria Seccia, Achille Cesare Pessina Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padua, Padua - Italy Primary aldosteronism - Part I: prevalence, screening, and selection of cases for adrenal vein sampling www.sin-italy.org/jnonline – www.jnephrol.com