Aldosterone-related biochemical phenotypes in adrenal incidentalomas: clinical relevance in a cohort including normotensive patients.

backgroundCurrent guidelines recommend screening for primary aldosteronism (PA) only in patients with hypertension and/or hypokalemia. However, recent evidence raises the question of whether normotensive patients with adrenal incidentalomas (AIs) might also exhibit biochemical features of aldosterone dysregulation. This study aimed to evaluate the prevalence and clinical significance of aldosterone-related abnormalities in normotensive patients with AIs.

methodsWe retrospectively analyzed 452 patients with AIs, of whom 202 were normotensive. Hormonal evaluation included plasma aldosterone concentration (PAC) and either plasma renin activity or concentration. The aldosterone-to-renin ratio (ARR) was considered elevated if > 20 when calculated with plasma renin activity or > 1.8 when using direct renin concentration. We performed comparative analyses according to blood pressure (BP) status, PAC, ARR, and combined aldosterone phenotypes (PAC > 10 ng/dL with elevated ARR, PAC > 10 ng/dL with normal ARR, and PAC ≤ 10 ng/dL with elevated ARR). Median follow-up was 3 years.

resultsNormotensive patients had a median age of 57 years (IQR 14), and 46.3% were male. Among them, 44.8% had PAC > 10 ng/dL and 33.3% had an elevated ARR. Serum potassium levels were within the normal range (median 4.3 mmol/L, IQR 0.5). In normotensive patients, no significant differences in systolic or diastolic BP were observed according to PAC or ARR alone. In the overall cohort, diastolic BP was higher in patients with elevated ARR. Importantly, diastolic BP differed significantly across combined aldosterone phenotypes (p = 0.015), with higher values observed in patients with PAC > 10 ng/dL and elevated ARR compared with those with PAC > 10 ng/dL and normal ARR (adjusted p = 0.048). During follow-up, incident hypertension was numerically higher among ARR-positive normotensive patients (18.4% vs. 11.0%), although this difference did not reach statistical significance (p = 0.215). A total of 10 patients were diagnosed with confirmed PA, including two normotensive individuals.

conclusionBiochemical evidence of aldosterone dysregulation is common in patients with AIs, including normotensive individuals. While isolated elevations in PAC or ARR were not associated with significant BP differences, the coexistence of elevated PAC and ARR identified a subgroup with a more pronounced hemodynamic profile. These findings support the concept of a continuum of aldosterone excess and suggest that combined biochemical phenotypes may be more informative than isolated markers. Further prospective studies are needed to clarify the clinical implications of these findings and to define optimal screening strategies in this population.