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PubMed This is a summary of 20 peer-reviewed journal articles Updated
Endocrinology · Primary Aldosteronism

Medical Management: Blocking the Hormone’s Effects

At a Glance

The primary treatment for bilateral primary aldosteronism is medication, usually mineralocorticoid receptor antagonists (MRAs) like spironolactone or eplerenone. Successful treatment requires not only lowering blood pressure but also normalizing renin levels to protect your heart and kidneys.

If testing shows that both of your adrenal glands are overproducing hormones (bilateral primary aldosteronism), surgery is generally not recommended [1]. Instead, the standard of care is targeted medical management. The goal is to “cancel out” the effects of the excess aldosterone to protect your heart, kidneys, and blood vessels from long-term damage [2].

The Shield: Mineralocorticoid Receptor Antagonists (MRAs)

The primary tools for managing bilateral PA are a class of drugs called Mineralocorticoid Receptor Antagonists (MRAs) [1]. You can think of these as a “shield.” While your body continues to produce too much aldosterone, these drugs sit on the “docking sites” (receptors) where the hormone would normally attach, blocking it from doing any harm [3].

There are two main types of MRAs used today:

  • Spironolactone: This is the most common and effective MRA [4]. However, it can sometimes block other hormones like testosterone. This may lead to side effects such as breast tenderness (gynecomastia) or sexual dysfunction [5][6].
  • Eplerenone: This is a newer, more “selective” MRA. It is designed to block aldosterone without affecting other hormones, making it a preferred choice for patients who experience side effects from spironolactone [7][8].

Beyond Blood Pressure: The PAMO Success Criteria

In the past, doctors often stopped adjusting medication as soon as a patient’s blood pressure looked “good.” Today, we use more rigorous standards called the PAMO (Primary Aldosteronism Medical Treatment Outcome) criteria [9].

Under PAMO, “complete success” means two things happen [9][10]:

  1. Clinical Success: Your blood pressure is normal.
  2. Biochemical Success: Your renin levels return to normal.

Remember, the “fingerprint” of PA is suppressed renin. If your renin stays low, it means the aldosterone is still winning the battle and your dose needs to be adjusted (titrated) upward [11]. Normalizing your renin is the only way to ensure your heart is fully protected from scarring and remodeling [12][13].

The Horizon: Aldosterone Synthase Inhibitors (ASIs)

While current MRAs act as a shield, a new class of “smarter” drugs is on the way. Aldosterone Synthase Inhibitors (ASIs), such as baxdrostat and lorundrostat, are currently in large-scale (Phase 3) clinical trials [14][15].

Rather than just blocking the hormone’s effects, these drugs stop the “factory” from producing aldosterone in the first place [16]. In early studies, they have shown incredible promise in lowering blood pressure for patients who haven’t responded to other treatments [17][18]. These medications represent the future of PA care, potentially offering better control with fewer side effects.

A Lifelong Partnership

Managing bilateral PA with medication requires regular check-ups. Because MRAs cause your body to hold onto potassium, your doctor will frequently monitor your blood to ensure you don’t develop hyperkalemia (too much potassium), especially when you are first starting or changing your dose [19][20]. With the right dose and consistent monitoring, medical therapy can be just as effective as surgery at reducing your risk of stroke and heart disease [2].

Common questions in this guide

Should I take spironolactone or eplerenone for primary aldosteronism?
Spironolactone is the most common and effective MRA, but it can cause side effects like breast tenderness. Eplerenone is a newer alternative that blocks aldosterone without affecting other hormones, making it a good choice if you experience side effects from spironolactone.
How do I know if my primary aldosteronism medication is working?
According to the PAMO criteria, complete success means your blood pressure is normal and your renin levels have returned to normal. If your renin remains low, your doctor may need to adjust your medication dose to ensure your heart is fully protected.
Why do I need blood tests while taking MRA medications?
MRAs can cause your body to hold onto too much potassium, a condition called hyperkalemia. Your doctor will frequently monitor your blood to check potassium levels and kidney function, especially when you are starting or changing your medication dose.
What are aldosterone synthase inhibitors (ASIs)?
ASIs are a new class of medications currently in clinical trials for primary aldosteronism. Instead of just blocking aldosterone's effects, these drugs are designed to stop your adrenal glands from producing excess aldosterone in the first place.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Should I be taking spironolactone or eplerenone, and what are the trade-offs regarding side effects?
  2. 2.What is my current renin level, and do we need to increase my MRA dose until my renin is no longer 'suppressed'?
  3. 3.How will we monitor my potassium and kidney function while we are adjusting (titrating) my medication?
  4. 4.Does my current medication plan meet the 'complete success' threshold of the PAMO criteria?
  5. 5.Am I a candidate for any clinical trials for new drugs like aldosterone synthase inhibitors (ASIs)?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (20)
  1. 1

    Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.

    Naruse M, Katabami T, Shibata H, et al.

    Endocrine journal 2022; (69(4)):327-359 doi:10.1507/endocrj.EJ21-0508.

    PMID: 35418526
  2. 2

    Aldosterone as a Mediator of Cardiovascular Damage.

    Buffolo F, Tetti M, Mulatero P, Monticone S

    Hypertension (Dallas, Tex. : 1979) 2022; (79(9)):1899-1911 doi:10.1161/HYPERTENSIONAHA.122.17964.

    PMID: 35766038
  3. 3

    Renoprotective Effects of Mineralocorticoid Receptor Antagonists Against Diabetic Kidney Disease.

    Bayne S, LeFevre J, Olstinske K, et al.

    Advanced biology 2024; (8(3)):e2300496 doi:10.1002/adbi.202300496.

    PMID: 38065929
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    Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association.

    Carey RM, Calhoun DA, Bakris GL, et al.

    Hypertension (Dallas, Tex. : 1979) 2018; (72(5)):e53-e90 doi:10.1161/HYP.0000000000000084.

    PMID: 30354828
  5. 5

    Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men's Issue?

    Manolis AA, Manolis TA, Melita H, Manolis AS

    Current hypertension reports 2019; (21(3)):22 doi:10.1007/s11906-019-0924-0.

    PMID: 30826898
  6. 6

    Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone.

    Lainscak M, Pelliccia F, Rosano G, et al.

    International journal of cardiology 2015; (200()):25-9.

    PMID: 26404748
  7. 7

    Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis.

    Elshahat A, Mansour A, Ellabban M, et al.

    BMC cardiovascular disorders 2024; (24(1)):489 doi:10.1186/s12872-024-04103-7.

    PMID: 39271992
  8. 8

    Mineralocorticoid receptor antagonist monotherapy in pediatric non-classical 11β-hydroxylase deficiency.

    Kennedy EC, Stack M, Carolan E, et al.

    Journal of pediatric endocrinology & metabolism : JPEM 2024; (37(12)):1100-1103 doi:10.1515/jpem-2024-0194.

    PMID: 39295130
  9. 9

    Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

    Yang J, Burrello J, Goi J, et al.

    The lancet. Diabetes & endocrinology 2025; (13(2)):119-133 doi:10.1016/S2213-8587(24)00308-5.

    PMID: 39824204
  10. 10

    Aldosterone-mineralocorticoid receptor interactions: new insights and therapeutic perspectives in primary aldosteronism.

    Yoshida Y, Shibata H

    Hypertension research : official journal of the Japanese Society of Hypertension 2026; (49(4)):1336-1342 doi:10.1038/s41440-026-02561-4.

    PMID: 41629686
  11. 11

    Predictors of treatment response to mineralocorticoid receptor antagonists in primary aldosteronism: insights from the SPAIN-ALDO registry.

    Goi J, Paja Fano M, Rizo Gellida A, et al.

    Journal of hypertension 2026; (44(9)):1530-1538 doi:10.1097/HJH.0000000000004365.

    PMID: 42267552
  12. 12

    Aldosterone and Impaired Nocturnal Blood Pressure Decline in Primary Aldosteronism.

    Liang NP, Li N, Wu H, et al.

    Journal of the American Heart Association 2026; (15(6)):e044976 doi:10.1161/JAHA.125.044976.

    PMID: 41804894
  13. 13

    Biochemical success after selective adrenal arterial embolization predicts long-term regression of aldosterone-mediated cardiac remodeling.

    Shuai WL, Zhang HC, Xiong HL, et al.

    American journal of hypertension 2026; (39(9)):1132-1141 doi:10.1093/ajh/hpag015.

    PMID: 41782336
  14. 14

    Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension: The Launch-HTN Randomized Clinical Trial.

    Saxena M, Laffin L, Borghi C, et al.

    JAMA 2025; (334(5)):409-418 doi:10.1001/jama.2025.9413.

    PMID: 40587141
  15. 15

    Breaking down resistance: novel aldosterone synthase inhibitors in the management of resistant hypertension.

    Eddison Chung Hung C, Kocherry C, George J

    Journal of hypertension 2025; (43(8)):1286-1295 doi:10.1097/HJH.0000000000004055.

    PMID: 40366087
  16. 16

    Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension.

    Freeman MW, Halvorsen YD, Marshall W, et al.

    The New England journal of medicine 2023; (388(5)):395-405 doi:10.1056/NEJMoa2213169.

    PMID: 36342143
  17. 17

    Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers.

    Freeman MW, Bond M, Murphy B, et al.

    Hypertension research : official journal of the Japanese Society of Hypertension 2023; (46(1)):108-118 doi:10.1038/s41440-022-01070-4.

    PMID: 36266539
  18. 18

    Aldosterone synthase inhibitors for resistant or uncontrolled hypertension: a network meta-analysis of randomized clinical trials.

    Elbahloul MA, Ali AHG, Al-Shammari AS, et al.

    Journal of hypertension 2026; (44(4)):542-552 doi:10.1097/HJH.0000000000004264.

    PMID: 41645642
  19. 19

    Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure.

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    PMID: 27057293
  20. 20

    Concomitant Enalapril and Spironolactone-Induced Hyperkalemia in a Pediatric Patient.

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This page provides educational information about medical management for primary aldosteronism. Always consult your endocrinologist or healthcare provider before starting, stopping, or adjusting any blood pressure medications.

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