Potential under-recognition of primary aldosteronism in young adults with hypertension

The aldosterone-to-renin ratio (ARR) is the primary screening test for primary aldosteronism (PA), but it is strongly influenced by renin activity, which varies with age. Fixed ARR thresholds may therefore under-recognize PA in younger adults. We retrospectively analyzed 14,750 hypertensive patients who underwent saline infusion testing for suspected PA. An ARR of 20 was consistently used as the local reference threshold, but confirmatory testing could proceed despite ARR < 20 when clinical suspicion was high. Baseline plasma renin activity (PRA), aldosterone concentration (ALD), and ARR were measured before saline infusion. Of 13,428 patients with calculable ARR, 8703 (64.8%) underwent saline infusion testing despite ARR < 20, and 1578 had confirmed PA. Among 3966 confirmed PA patients with classifiable age-ARR data, ARR < 20 occurred in 57.5, 50.6, 35.4, and 33.2% of patients aged <35, 35-44, 45-54, and ≥55 years, respectively. Increasing age remained associated with lower odds of ARR < 20 after adjustment for sex, body mass index, blood pressure, potassium, creatinine, and a documented adrenal nodule (adjusted OR per year, 0.975; 95% CI, 0.967-0.984). The gradient persisted after restricting analyses to patients without a documented adrenal nodule, with potassium ≥3.5 mmol/L and eGFR ≥60 mL/min/1.73 m². Younger adults with confirmed PA frequently had baseline ARR values below 20, largely with relatively preserved PRA. Although residual referral bias cannot be excluded, these findings support cautious, age-informed interpretation of ALD, PRA, and ARR.