The aldosterone-to-renin ratio (ARR) is widely accepted as the preferred screening test for primary aldosteronism (PA). Although a suppressed renin is considered a hallmark of PA, patients with non-suppressed renin and a falsely negative ARR have been reported that would have been missed if the recommended diagnostic pathway was followed. This report describes eight patients (2 women and 6 men, median age 48 [range 35-63]) with a proven aldosterone-producing adenoma (APA) but a non-suppressed renin (PRC > 8.4 mU/L). Their systolic and diastolic blood pressures on referral were 157 (114-195) and 103 (74-119) mmHg on 2.5 (1-6) antihypertensives. Five were on potassium-sparing diuretics and/or potassium replacement. After medication adjustment to agents known to have minimal effect on renin and aldosterone levels, PRC, PAC and ARR were 18.5 (9-43) mU/L, 780 (270-1940), and 47 (8-78, normal <75), respectively. Seven patients had two consecutive ARR measurements and five of them had two negative tests. Renal artery stenosis (RAS) was carefully ruled out in all patients. Further evaluation for PA was pursued because of high clinical suspicion (hypokalaemia and/or an adrenal mass lesion on imaging). Five patients underwent a suppression test and although aldosterone did not suppress, renin also failed to suppress. All underwent adrenal vein sampling confirming unilateral PA. Seven were managed with unilateral adrenalectomy and one is awaiting surgery. Postsurgical follow-up data were available for seven patients. Three had a postoperative suppression test confirming biochemical cure; the other four displayed an excellent clinical or biochemical response.
Many known and unknown factors influence the ARR. Strict control of these factors is crucial to avoid false-negative results. Other causes that could explain a non-suppressed renin should be ruled out. In patients with a consistently non-suppressed renin further diagnostic workup for PA should be considered if clinical suspicion remains high.