The Spectrum from Overt Primary Aldosteronism to Mild Dysregulated Aldosterone Production in Incidentally Discovered Adrenocortical Adenomas

Abstract

Background: Incidental adrenocortical adenomas (IA) are common. Current guidelines suggest screening for primary aldosteronism (PA) only in cases of hypertension or hypokalemia. This study aimed to evaluate the spectrum from overt PA to mild dysregulated aldosterone production with a sensitive protocol irrespective of blood pressure (BP) and potassium in patients with IA. Methods: 254 consecutive patients (excluding hypercortisolism) were evaluated. The spectrum of PA was defined as a suppressed renin plus the following criteria: 1)Overt PA: aldosterone-to-renin-ratio (ARR) >30 ng/dL-to-ng/mL/hr, plasma aldosterone concentration (PAC) >15ng/dL, and/or 24h urinary aldosterone >10 ug/24h; 2)Moderate PA: ARR 20-30 ng/dL-to-ng/mL/hr, PAC 10-15 ng/dL; 3)Mild dysregulated aldosterone production: ARR <20 ng/dL-to-ng/mL/hr and PAC >5-10 ng/dL. Results: 35% (n=89/254) met criteria for PA spectrum, 20% (34/89) were initially normotensive and 94% (84/89) normokalemic. Overt, moderate, and mild groups were 10%, 12%, and 13%. There were trends across groups of clinical severity: systolic BP (153±19, 140±14, 137±14 mmHg, p-trend<0.05), resistant hypertension (50%, 23%, 7% p-trend=<0.001), daily defined dose of antihypertensives (DDD) (3.2±1.6, 1.2±1.5, 0.4±0.6 p-trend=0.001), and lower eGFR (75.5±30.8, 97.8±38.5, 101±25.5, p-trend<0.01). At follow-up (mean 28±15 months), 87% had treatment with MR antagonists or surgery with decreased systolic BP relative to clinical severity, -31.3 ±23, -12.7 ±19, and -11.4 ±19 mmHg, (p-trend<0.001). Similar trends were observed for DDD, with significant increase in renin. Conclusions: There is a prevalent spectrum of clinically-relevant PA and dysregulated aldosterone production in IA, irrespective of BP or potassium, usually undetected. Aldosterone-directed treatment improved BP and normalized renin even in milder cases.