Should Medications Be Stopped Before Aldosteronism Screening?

Whether medications that affect the renin-angiotensin-aldosterone system should routinely be withdrawn before screening for primary aldosteronism (PA) remains unsettled, according to an expert debate in The Journal of Clinical Endocrinology & Metabolism.

Antihypertensive drugs can alter renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR). Beta-blockers may raise the ratio by suppressing renin, producing false-positive results. Mineralocorticoid receptor antagonists, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers may lower it, potentially producing false negatives.

Christina Pamporaki and Jacques Lenders argue for withdrawal or substitution of interfering drugs when safe and feasible, particularly in patients with moderate or high pretest probability of PA. They emphasize that a false-negative result can end further diagnostic evaluation and delay targeted treatment. They illustrate medication interference with two cases: an initially false-positive result during bisoprolol treatment and a false-negative result during spironolactone treatment.

Ada Teo and Morris Brown argue that routine withdrawal is unnecessary for most patients. They emphasize that medication adjustment can worsen hypertension or hypokalemia, delay testing, and create barriers to diagnosis. They cite a retrospective analysis of 1,306 patients in which screening without medication withdrawal achieved sensitivity up to 97.7% and a negative predictive value of 99%.

The authors describe the 2025 Endocrine Society guideline as allowing testing on existing treatment, partial substitution, or complete withdrawal, depending on safety and feasibility. They also acknowledge that much of the evidence is retrospective or observational and frequently measures biochemical changes rather than clinical outcomes. The authors call for prospective trials to clarify diagnostic approaches and establish the long-term benefits of aldosterone-targeted therapy.

Source: Teo AED, Pamporaki C, Lenders JWM, Brown MJ. Must RAAS-modifying drugs be withdrawn for the diagnosis of primary aldosteronism? J Clin Endocrinol Metab. 2026;dgag375. doi:10.1210/clinem/dgag375