Interpreting Serial Aldosterone-to-Renin Ratio Measurements in the Diagnostic Work-up of Primary Aldosteronism

Guidelines recommend repeating aldosterone-to-renin ratio (ARR) testing when clinical suspicion of primary aldosteronism (PA) remains high, but evidence-based guidance on how serial ARR measurements should be interpreted is lacking.

To compare alternative strategies for interpreting serial ARR measurements during the diagnostic work-up of PA.

We retrospectively studied patients evaluated for PA at a referral centre for endocrine hypertension who had two valid ARR measurements. Diagnostic performance was compared for ARR1, the mean of ARR1 and ARR2, at least one positive ARR, and two concordant positive ARR results using different thresholds. Additional analyses evaluated concordant and discordant patterns and progressively more stringent biochemical definitions.

Among 342 patients with two serial ARR measurements, 214 (62.6%) had PA. Different interpretation strategies produced distinct trade-offs between sensitivity and specificity. At an ARR threshold of 49, requiring both measurements to be positive achieved the highest balanced accuracy (77.1%), with 82.2% sensitivity and 71.9% specificity. PA prevalence increased from 21.3% in patients with two negative ARR measurements to 83.0% in those with two positive measurements, whereas both discordant patterns showed an intermediate probability of PA (36.8% and 36.0%). Averaging the first two ARR measurements modestly improved discrimination across progressively more stringent operational biochemical definitions, with the AUC increasing from 0.772 to 0.803 for ARR ≥49 plus post-SST SAC ≥100 ng/L (p = 0.015).

Serial ARR measurements provide complementary rather than interchangeable information. Different interpretation strategies offer distinct diagnostic trade-offs, whereas discordant results identify an intermediate-probability group requiring integration with the overall clinical context.