Comparing ARR Versus Suppressed PRA as Screening Tests for Primary Aldosteronism.

Background: In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR.

Who and How Should We Screen for Primary Aldosteronism?

There are mounting data that at least 30% of hypertensives who are appropriately screened have primary aldosteronism (PA), rather than the commonly reported figure of 5% to 10%. Second, there are similar data that undertreated patients with PA have a 3-fold higher risk profile than essential hypertensives with the same blood pressure levels. Third, clinicians managing hypertension measure success as sustainable lowering of blood pressure; untreated hypertensive patients with PA are thus in double jeopardy.

Primary Aldosteronism: Where Are We Now? Where to From Here?

Primary aldosteronism, the most common secondary form of hypertension, is thought to be present in ≈5% to 10% of hypertensive adults. However, recent studies indicate that its prevalence may be at least 3-fold higher based on the identification of renin-independent (autonomous) aldosterone production that is not suppressible with dietary sodium loading in a large fraction of adults with primary hypertension. Currently, the screening rate for primary aldosteronism in adults with primary hypertension is <1%.

A tumour suppressive relationship between mineralocorticoid and retinoic acid receptors activates a transcriptional program consistent with a reverse Warburg effect in breast cancer.

Background: The role of nuclear receptors in both the aetiology and treatment of breast cancer is exemplified by the use of the oestrogen receptor (ER) as a prognostic marker and treatment target. Treatments targeting the oestrogen signalling pathway are initially highly effective for most patients. However, for the breast cancers that fail to respond, or become resistant, to current endocrine treatments, the long-term outlook is poor.

Primary Aldosteronism: Where Are We Now? Where to from Here?

The past nine years have seen major advances in establishing the etiology of unilateral primary aldosteronism, and very possibly that of bilateral hyperaldosteronism, in response to somatic mutations in aldosterone synthase expressing cells. Though there have been important advances in the management of primary aldosteronism, in small but convincing studies, they represent minor changes to current guidelines. What has been totally absent is consideration of the public health issue that primary aldosterone represents, and the public policy issues that would be involved in addressing the disorder.

Primary Aldosteronism: Present and Future.

Primary aldosteronism (PA), currently recognized to be 5-10% of hypertension, has a cardiovascular risk profile double that in age-, sex-, and blood pressure-matched essential hypertensives. Screening for PA is by determining the plasma aldosterone to renin ratio (ARR), followed by one of half a dozen confirmatory/exclusion tests. Unilateral hyperaldosteronism normally reflects an aldosterone producing adenoma; bilateral disease is the more common form, and termed idiopathic hyperaldosteronism (IHA).

Aldosterone Research: 65 Years, and Counting.

Aldosterone was characterized as the major mineralocorticoid hormone 65 years ago, and since then its physiologic role in epidural electrolyte homeostasis the province of nephrologists. In epithelia it acts via the mineralocorticoid receptor (MR) to retain Na and excrete K; MRs, however, are widely expressed in organs not known to be aldosterone target tissues. MRs are not merely "aldosterone receptors," as they have equivalently high affinity for the physiologic glucocorticoids, and for progesterone.

Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency.

Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene () cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the gene result either in severe AME or a milder phenotype (type 2 AME).

Primary Aldosteronism: The Next Five Years.

The management of primary aldosteronism is widely varied within various published guidelines, with very little in the way of data supporting the choice of one variation over others. Current estimates of prevalence are probably accurate for aldosterone producing adenoma, but fall very short of that for bilateral adrenal hyperplasia. Discovery at the level of basic science has proven illuminating over the past 6 years in terms of unilateral disease and both somatic and germline mutations, with much less focus on the much more common bilateral disease; Attempts at harmonization have begun - for example, criteria for complete/partial/absent cure after adrenalectomy for unilateral disease; again focus on bilateral disease is muted.

Spironolactone in cardiovascular disease: an expanding universe?

Spironolactone has been marketed for over half a century as a 'potassium-sparing diuretic', used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction.