Emerging Medical Therapies for Primary Aldosteronism

Medical therapy for primary aldosteronism has been stagnant for decades, relying on mineralocorticoid receptor antagonists, which block downstream signaling of aldosterone rather than aldosterone production. This approach typically leads to reactive elevation of aldosterone production, and possible implications of its nongenomic effects. In addition, steroidal mineralocorticoid receptor antagonist use is limited by cross-reactivity with other nuclear receptors and concern for hyperkalemia, particularly in kidney insufficiency. These limitations have propelled a rising interest in therapies that suppress aldosterone production. Aldosterone synthase inhibitors directly target aldosterone synthase overexpression and aldosterone excess. This review presents the evolving landscape of primary aldosteronism therapies, including emerging aldosterone synthase inhibitors and nonsteroidal mineralocorticoid receptor antagonists, and it presents a perspective on expected benefits and limitations of these emerging classes.