PROGRESS IN ALDOSTERONISM: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension

Abstract

Primary aldosteronism (PA) secondary to excessive and/or autonomous aldosterone secretion from the renin-angiotensin system accounts for w10% of cases of hypertension and is primarily caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenomas (APAs). Although the diagnosis has traditionally been supported by low serum potassium levels, normokalaemic and even normotensive forms of PA have been identified expanding further the clinical phenotype. Moreover, recent evidence has shown that serum aldosterone correlates with increased blood pressure (BP) in the general population and even moderately raised aldosterone levels are linked to increased cardiovascular morbidity and mortality. In addition, aldosterone antagonists are effective in BP control even in patients without evidence of dysregulated aldosterone secretion. These findings indicate a higher prevalence of aldosterone excess among hypertensive patients than previously considered that could be attributed to disease heterogeneity, aldosterone level fluctuations related to an ACTH effect or inadequate sensitivity of current diagnostic means to identify apparent aldosterone excess. In addition, functioning aberrant receptors expressed in the adrenal tissue have been found in a subset of PA cases that could also be related to its pathogenesis. Recently a number of specific genetic alterations, mainly involving ion homeostasis across the membrane of zona glomerulosa, have been detected in w50% of patients with APAs. Although specific genotype/phenotype correlations have not been clearly identified, differential expression of these genetic alterations could also account for the wide clinical phenotype, variations in disease prevalence and performance of diagnostic tests. In the present review, we critically analyse the current means used to diagnose PA along with the role that ACTH, aberrant receptor expression and genetic alterations may exert, and provide evidence for an increased prevalence of aldosterone dysregulation in patients with essential hypertension and pre-hypertension.

A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism

“…The prevalence of PA varies considerably among hypertensive patients in different studies, depending on patient selection, diagnostic methodology employed, and severity of arterial hypertension (1,2,3,4).…”

The prevalence of primary aldosteronism (PA) in a group of 350 hypertensive patients

“…To reduce the proportion of both false positive rates and false negative, it is essential to eliminate the effects negative factors affecting the RAAS. The estimation specificity of ARR varies from 71-84% with sensitivity ranging from 73% to 93%, whereas the prevalence of PA was found to be 13% [9].…”

“…Most commonly PA is due to bilateral adrenal hyperplasia (BAH) of zona glomerulosa; less frequent is an aldosterone producing adenoma (APA) -classic Conn's syndrome [9]. Other cause of PA are even more rare, such as cancer (about 1%), ectopic secretion of aldosterone (approx.…”

“…1%) (the so-called 1% rule) [10]. Recently, in approximately 50% of patients with APA specific genetic alteration have been detected [9].…”

“…However, a 10% prevalence of PA was found among hypertensive patients in prospective studies, and this figure raised to around 30% when aldosterone-renin ratio (ARR) was used as a screening test by general practitioner [9]. Gordon et al (1994) in one of the most important reports found PA in 8.5% of 199 patients with normokalaemic hypertension [14].…”