Low-renin hypertension in incidental adrenal adenomas and response to aldosterone-targeted therapy: a prospective...

Incidental adrenal adenomas are common, yet renin status is infrequently assessed in hypertensive patients. Emerging evidence supports a spectrum of renin-independent aldosterone excess associated with adverse cardiovascular risk.

To determine the frequency of a low-renin phenotype in a prospective cohort of hypertensive patients with adrenal adenomas and to evaluate the clinical response to aldosterone-targeted therapy across baseline aldosterone categories. Low-renin phenotype was defined as suppressed renin (PRA <1.0 ng/mL/h or DRC <10 µIU/mL). Among these patients, plasma aldosterone concentration (PAC) was categorized as 5-10 ng/dL (Group 1), 10-15 ng/dL (Group 2), and >15 ng/dL (Group 3). Patients with suppressed renin were treated with MR antagonists or adrenalectomy and followed longitudinally using PAMO/PASO criteria.

Low renin was present in 47% (138/290) of hypertensive patients. Increasing aldosterone levels were associated with higher systolic blood pressure (SBP), resistant hypertension, higher antihypertensive treatment burden, lower potassium, and reduced eGFR (p-trend <0.001). After a mean follow-up of 24±18 months (n = 121), aldosterone-targeted therapy (75% medical, 25% surgical) led to significant reductions in SBP (-18, -26, and -30 mmHg across Groups 1-3; all p < 0.001), decreased medication and significant increases in renin (all p < 0.001), irrespective of aldosterone category.

Nearly half of hypertensive patients with adrenal incidentalomas exhibit suppressed renin levels associated with greater blood pressure burden and favorable response to aldosterone-targeted therapy, even in lower aldosterone levels categories. These findings support systematic renin assessment in hypertensive patients with incidental adrenal adenomas and provide a rationale for testing aldosterone-targeted therapy in broader hypertensive populations beyond adrenal adenomas.