Is It Time to Retire Aldosterone Suppression Testing?

Primary aldosteronism (PA) is the most common endocrine hypertension. For decades, PA diagnosis has required proving nonsuppressibility of aldosterone following maneuvers modulating the renin-angiotensin-aldosterone pathway. This includes oral salt suppression, intravenous saline suppression, captopril suppression, and others. Grounded in rational first principles from pathophysiologic considerations and small, early pathophysiologic studies following Conn's initial PA description, such testing has been widely recommended. However, a modern understanding of PA pathophysiology and critical appraisal of diagnostic test studies suggest that traditional suppression testing is not suited to diagnosis or disease definition. There are four main problems recently raised regarding aldosterone suppression testing: (i) PA is now known to exist along a continuous biochemical spectrum and it is scientifically impossible to draw a single, diagnostic threshold within this continuum. (ii) Aldosterone assay uncertainty is sufficiently large to yield contradictory final diagnoses when applied to a threshold during suppression testing. (iii) The pathophysiology of PA is multifactorial with multiple mechanisms not necessarily relevant to salt and volume loading tests. (iv) Finally, meta-analysis of suppression testing studies demonstrated extensive biases and confounders, which have overestimated the diagnostic value. A recent prospective, blinded study of saline suppression for PA diagnosis defined by medical or surgical response to PA-targeted therapy showed no discrimination according to nadir aldosterone level. Given the clinical value of a PA diagnosis and the high prevalence of the disease, modern evidence suggests that aldosterone suppression testing should now be retired from the diagnostic pathway; new ways of approaching the definition of PA are provided to spur further discussion.