Key result
Two positive serial ARR measurements achieve ~77% balanced accuracy for diagnosing primary aldosteronism.
Why the study?
Guidelines recommend repeating aldosterone-to-renin ratio testing when clinical suspicion of primary aldosteronism remains high, but evidence-based guidance on interpreting serial ARR measurements is lacking.
How do different interpretation strategies for serial aldosterone-to-renin ratio (ARR) measurements affect diagnostic performance for primary aldosteronism?
Cohort (n=342)
No
How do different interpretation strategies for serial aldosterone-to-renin ratio (ARR) measurements affect diagnostic performance for primary aldosteronism?
In the diagnostic work-up of primary aldosteronism, requiring two concordant positive serial ARR measurements maximizes diagnostic accuracy, while discordant results indicate an intermediate probability requiring clinical integration.
May support two concordant positive serial ARRs to refine PA diagnosis in referrals; hypothesis-generating and needs prospective validation before practice change.
CONTEXT: 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. OBJECTIVE: To compare alternative strategies for interpreting serial ARR measurements during the diagnostic work-up of PA. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Parasiliti-Caprino et al. (2026) conducted a cohort in Primary aldosteronism (n=342). Serial aldosterone-to-renin ratio (ARR) measurements vs. Alternative interpretation strategies was evaluated on Balanced accuracy for diagnosing primary aldosteronism requiring both serial ARR measurements to be positive at a threshold of 49. Requiring two serial aldosterone-to-renin ratio measurements to be positive at a threshold of 49 achieved 77.1% balanced accuracy for diagnosing primary aldosteronism.
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