The syndromes of low-renin hypertension: "separating the wheat from the chaff"

Abstract

Primary aldosteronism (PA) is characterized by hypertension and suppressed renin activity with or without hypokalemia and comprises the aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia or idiopatic hyperaldosteronism (IHA). In recent series employing the aldosterone (aldo, ng/dL):renin (ng/mL·h) ratio (ARR) for screening, prevalence of PA among hypertensives soars to 8-20%; current predominance of IHA (>80%) over APA suggests the inclusion of former low-renin essential hypertensives (LREH), in whom plasma aldo can be reduced by suppressive maneuvers. We evaluated the test characteristics of the ARR obtained retrospectively from 127 patients with PA (81 APA; 46 IHA) and 55 with EH (30 LREH; 25 NREH) studied from 1975 to 1990. Using the combined ROC-defined cutoffs of 27 for the ARR and 12ng/dL for aldo, we obtained 89.8% sensitivity (Ss) and 98.2% specificity (Sp) in discriminating PA from EH: all APA and 72% of the IHA patients had values above these limits, but only one (3%) with LREH. Among the 46 IHA patients, 10 (21.7%) had ARR <27, four of whom with aldo <12ng/dL, virtually indistinguishable from LREH. Use of higher cutoff values (ARR >100; aldo >20) may attain 84%Ss and 82.6%Sp in separating APA from IHA. Because IHA and LREH ("the chaff") may be spectrum stages from the same disease, definite discrimination between these entities seems immaterial. However, precise identification of the APA ("the wheat") is critical, since it is the only surgically curable form of PA. Thus, while patients who may harbor an APA must be thoroughly investigated and surgically treated, non-tumoral disease (IHA and LREH) may be best treated with an aldo-receptor antagonist that will also prevent the aldo-mediated inflammatory effects involved in myocardial fibrosis and abnormal cardiac remodeling.