OBJECTIVE: Primary aldosteronism (PA) is form of hypertension characterized by production of aldosterone by the adrenal that is excessive and relatively autonomous of the renin-angiotensin system. Once detected, unilateral PA can be usually cured by surgical removal of the affected adrenal, while bilateral PA can be specifically treated by medications, which antagonize aldosterone action. Clinical guidelines of Endocrine Societies in Europe and the US recommend screening for PA among most hypertensive patients. The incidence of PA among hypertensive patients varies from 5-30% between different studies. This may be due, at least in part, to variability in screening approaches and assay performance.

DESIGN AND METHOD: There is an urgent need for a versatile PA screening approach that doesn't require withdrawal of potentially interfering medications and therefore allows the clear identification of PA patients without potentially complex and risky treatment amendments being necessary during the course of the diagnostic process. The Aldosterone-to-Angiotensin-II-Ratio (AA2-Ratio) is a novel LC-MS/MS based high-throughput test for PA that combines the plasma levels of aldosterone and physiologically active angiotensin II into a diagnostic ratio.

RESULTS: The AA2-Ratio has the potential to be superior to the ARR in terms of its ability to discriminate between PA and other forms of hypertension, accuracy in measuring aldosterone, better reflecting the activity of the true direct circulating regulator of aldosterone (i.e. angiotensin II rather than renin), and being less affected by antihypertensive medications including ACE inhibitors. First data obtained in a proof-of-concept study investigating PA positive and negative patients proved the AA2-Ratio to be a powerful and cost-effective diagnostic tool for the diagnosis of PA among hypertensives.

CONCLUSIONS: The availability of novel diagnostic approaches for the Renin-Angiotensin-Aldosterone-System (Equilibrium Analysis) might pave the way for Angiotensin peptides to be used in clinical routine testing by solving pre-analytic problems of analyte stability.