What New Treatment Options Exist for Primary Aldosteronism?

Important Note: The standard of care for bilateral primary aldosteronism remains mineralocorticoid receptor antagonists (MRAs) like spironolactone or eplerenone. The new medications and procedures discussed on this page—including aldosterone synthase inhibitors (ASIs) and nonsteroidal MRAs—are investigational or off-label for this condition. Never change or stop your medications without consulting your healthcare provider.

If you have bilateral primary aldosteronism (where both adrenal glands overproduce aldosterone) or are not a candidate for surgery, lifelong medical therapy is usually required ^[1]. The standard treatment is a mineralocorticoid receptor antagonist (MRA) such as spironolactone, alongside a diet low in sodium ^[1][2].

While spironolactone is effective, it can cause frustrating sex-hormone-related side effects, particularly in men (such as breast enlargement and loss of libido) ^[3]. When these occur, doctors often switch patients to eplerenone, an established, more selective MRA that causes fewer of these side effects ^[4].

However, researchers are also actively testing new investigational treatments—most notably a class of drugs called aldosterone synthase inhibitors (ASIs)—to provide more options for patients whose condition is not fully controlled or who cannot tolerate current therapies.

How Aldosterone Synthase Inhibitors Work

Current MRAs (spironolactone and eplerenone) are potassium-sparing medicines that block the downstream receptors that aldosterone normally targets ^[5]. While this prevents aldosterone from doing damage, your body notices the blockade and can react by producing even more aldosterone ^[6].

Aldosterone synthase inhibitors (ASIs), such as baxdrostat and lorundrostat, work through a different mechanism. They target and inhibit a specific enzyme (CYP11B2) that your adrenal glands use to manufacture aldosterone ^[5]. By inhibiting this enzyme, ASIs are designed to lower the actual amount of aldosterone circulating in your blood ^[6].

A major challenge with these drugs is ensuring they only stop aldosterone and not cortisol, a vital stress hormone produced by a nearly identical enzyme ^[7]. In laboratory studies, newer ASIs demonstrate a strong selectivity for the aldosterone enzyme ^[8]. However, because clinical trials are still ongoing, it is not yet guaranteed that cortisol production is perfectly preserved in every patient. Patients in these trials are carefully monitored for signs of cortisol suppression (adrenal insufficiency) ^[5].

Potential Benefits for Bilateral Disease

Because ASIs target the synthesis of aldosterone directly, they do not act on the androgen and progesterone receptors the way spironolactone does ^[9]. This means they may avoid the sexual and hormonal side effects associated with traditional MRAs ^[7]. However, long-term safety, cardiovascular benefits, and head-to-head comparisons against standard MRAs have not yet been established ^[10].

Clinical Trials for ASIs

Clinical trials are currently evaluating these medications (check official registries like ClinicalTrials.gov for the most up-to-date enrollment status):

• Baxdrostat: In an early Phase II clinical trial called SPARK-PA, baxdrostat was reported to reduce blood pressure and improve biochemical markers in patients with confirmed primary aldosteronism ^[11]. Based on these early results, a larger Phase III trial program (BaxPA) is being conducted to further evaluate its safety and effectiveness ^[11].
• Lorundrostat: Lorundrostat has been studied in resistant or uncontrolled hypertension trials. For example, in the Phase III Launch-HTN trial (NCT06153693), a 50 mg dose provided a 9.1-mmHg placebo-adjusted reduction in systolic blood pressure at 6 weeks ^[12]. However, lorundrostat has not yet been established in trials specifically for biochemically confirmed primary aldosteronism, and its use for this condition remains investigational ^[13].

Risks and Required Monitoring

Manipulating the aldosterone pathway carries significant risks related to the body’s fluid and electrolyte balance. In clinical trials, ASIs have been associated with:

• Hyperkalemia (High Potassium): Elevated blood potassium can cause dangerous heart rhythm problems ^[14].
• Reduced Kidney Function: Modest declines in estimated glomerular filtration rate (eGFR), which require close clinical interpretation by a doctor ^[15][16].
• Hyponatremia (Low Sodium): Drops in blood sodium levels ^[15][16].

Important Safety Warning: If you are taking MRAs or participating in an ASI trial, frequent monitoring of your potassium, kidney function, and blood pressure is essential ^[2]. Do not use potassium supplements or potassium-enriched salt substitutes, as these can cause severe hyperkalemia when combined with these medications.

Other Emerging Alternatives

Beyond ASIs, researchers are exploring other experimental options:

• Nonsteroidal MRAs (Finerenone): In an early 12-week, single-arm study of 57 patients with primary aldosteronism, finerenone lowered blood pressure and improved potassium levels ^[9]. However, larger, randomized head-to-head trials against spironolactone are needed before it can be considered a standard substitute ^[9].
• Procedural Interventions: For highly selected patients with bilateral disease treated at specialized centers, early experimental procedures like catheter-based adrenal ablation and superselective adrenal arterial embolization are being tested ^[17][18]. While small, non-randomized studies show potential, these are not established standard treatments. They carry serious potential risks, including bleeding, contrast-related kidney injury, non-target tissue damage, and unintended adrenal insufficiency ^[18].