If your blood pressure remains stubbornly high despite taking three or more medications, there is a reasonable chance your doctor has missed the real problem. Primary aldosteronism — a hormonal condition in which the adrenal glands produce too much aldosterone — is now estimated to affect roughly 40 million American adults, yet up to 95 percent of cases go undiagnosed for years. These patients are typically labeled as having “essential hypertension” and cycled through escalating drug regimens that never fully work, because the underlying cause is never identified. Two new drugs, baxdrostat and lorundrostat, represent the first medications designed to shut down excess aldosterone production at its source, and early trial results suggest they may finally offer a targeted solution for millions of people stuck on ineffective treatment plans. Consider a patient in her fifties who has been on four blood pressure medications for a decade.
Her readings still hover around 160/95. She has been told she has “resistant hypertension” and that some people simply do not respond well to treatment. What she has never been told is that a single morning blood test measuring aldosterone and renin levels could reveal the actual driver of her condition. A California study of 4,660 patients with resistant hypertension found that only 2.1 percent were ever screened for primary aldosteronism — a staggering failure given that the condition affects 20 to 30 percent of patients in that exact population. This article covers the scale of the missed diagnosis crisis, the new 2025 screening guidelines that could change everything, and the two breakthrough drugs now racing toward FDA approval.
Table of Contents
- Why Is Primary Aldosteronism Missed in Millions of Hypertension Patients?
- The 2025 Endocrine Society Guidelines That Could Change Screening Forever
- How Excess Aldosterone Damages the Brain and Body
- Baxdrostat and Lorundrostat — Comparing the Two New Aldosterone Synthase Inhibitors
- Why Spironolactone Falls Short and What the New Drugs Fix
- What Caregivers and Families Should Watch For
- What Comes Next for Primary Aldosteronism Treatment
- Conclusion
- Frequently Asked Questions
Why Is Primary Aldosteronism Missed in Millions of Hypertension Patients?
Primary aldosteronism has been called “one of the most significant missed opportunities in modern cardiovascular medicine,” and the numbers back that up. The condition is present in 5 to 14 percent of all hypertension patients seen in primary care and up to 30 percent of those referred to specialty clinics. Yet because most physicians were trained to view it as a rare disorder — a relic of medical school lectures about obscure adrenal tumors — screening rates remain dismal. The disconnect between how common the condition actually is and how rarely doctors look for it has created a public health gap affecting tens of millions of people. The consequences of this diagnostic blind spot extend far beyond uncontrolled blood pressure. Undiagnosed primary aldosteronism is associated with significantly elevated rates of stroke, heart failure, coronary artery disease, atrial fibrillation, diabetes, renal failure, and obstructive sleep apnea. Research published in the AHA’s Hypertension journal has documented these associations, and studies in Frontiers in Cardiovascular Medicine report that 14 to 35 percent of PA patients develop serious cardiovascular complications including myocardial hypertrophy and fibrosis.
These are not theoretical risks. They are measurable organ damage accumulating in patients who believe they are being adequately treated because they are taking their pills every morning. Part of the problem is structural. Primary care physicians manage the vast majority of hypertension cases, and most do not have aldosterone screening built into their diagnostic workflows. The test itself is straightforward — a morning seated blood draw measuring serum aldosterone and plasma renin — but it requires the physician to suspect the condition in the first place. When a patient’s blood pressure does not respond to standard medications, the reflexive response in most clinical settings is to add another drug rather than question the diagnosis. This prescribing-first, testing-later approach has allowed primary aldosteronism to hide in plain sight for decades.
The 2025 Endocrine Society Guidelines That Could Change Screening Forever
In July 2025, the Endocrine Society published a landmark update to its clinical practice guidelines for primary aldosteronism, and the central recommendation was a dramatic departure from previous guidance. The updated guideline now recommends screening all individuals with hypertension for PA — not just the high-risk subgroups that prior guidelines had targeted. This conditional recommendation was co-sponsored by the American Heart Association, the European Society of Hypertension, the European Society of Endocrinology, the American Association of Clinical Endocrinology, the International Society of Hypertension, and the Primary Aldosteronism Foundation, lending it unusual cross-organizational weight. The recommended screening method is practical enough for any primary care office: a morning seated measurement of serum aldosterone and plasma renin, with a concurrent potassium level drawn at the same time. Previous guidelines had limited screening recommendations to patients with resistant hypertension, unexplained hypokalemia, adrenal incidentalomas, or early-onset hypertension.
The problem with that narrower approach was that it missed the majority of PA patients, who often present with normal potassium levels and whose hypertension looks, on the surface, like the garden-variety kind. By expanding the screening recommendation to all hypertensive patients, the guideline acknowledges that the old strategy of screening only “suspicious” cases was failing catastrophically. However, translating a guideline into clinical practice is never instantaneous, and there are real barriers to universal adoption. Many primary care practices are already stretched thin, and adding a screening test to every hypertension visit will require workflow changes, lab coordination, and physician education. There is also the question of what happens after a positive screen — confirmatory testing and subtype classification require endocrinology referral, and the specialist workforce may not be prepared for the volume of new referrals that widespread screening would generate. The guideline is a necessary first step, but it will take years of implementation effort before screening rates meaningfully improve from the current 2 percent baseline.
How Excess Aldosterone Damages the Brain and Body
For readers of a brain health and dementia care site, the connection between primary aldosteronism and cognitive decline deserves particular attention. chronic uncontrolled hypertension is one of the strongest modifiable risk factors for vascular dementia and contributes to the progression of Alzheimer’s disease. When the underlying cause of that hypertension is a treatable hormonal excess that goes unaddressed for a decade or more, the cumulative vascular damage to the brain is substantial and potentially irreversible. Aldosterone does not merely raise blood pressure by causing the kidneys to retain sodium and water. It also drives inflammation and fibrosis in blood vessel walls, the heart muscle, and the kidneys independently of its blood pressure effects.
Research has documented that PA patients suffer disproportionate cardiovascular damage compared to patients with the same degree of blood pressure elevation from other causes. This means that even when PA patients achieve partial blood pressure control through standard antihypertensive medications, the excess aldosterone continues to inflict direct tissue damage that those medications do nothing to address. A specific and instructive example involves the relationship between PA and atrial fibrillation. Patients with undiagnosed primary aldosteronism develop atrial fibrillation at markedly higher rates than matched hypertensive controls, and atrial fibrillation itself is a major independent risk factor for stroke and vascular dementia. The mechanism is direct: excess aldosterone causes fibrotic remodeling of the atrial tissue, creating the structural substrate for arrhythmia. For an older adult already at risk for cognitive decline, this chain of events — missed PA diagnosis leading to atrial fibrillation leading to stroke or chronic cerebral hypoperfusion — represents a preventable cascade that current screening practices are allowing to unfold in millions of patients.
Baxdrostat and Lorundrostat — Comparing the Two New Aldosterone Synthase Inhibitors
The two drugs furthest along in development for primary aldosteronism and aldosterone-driven hypertension are baxdrostat, developed by AstraZeneca, and lorundrostat, developed by Mineralys Therapeutics. Both belong to the same new drug class — aldosterone synthase inhibitors — which work by blocking CYP11B2, the specific enzyme responsible for producing aldosterone. This mechanism is fundamentally different from existing treatments like spironolactone, which block the aldosterone receptor downstream rather than preventing aldosterone from being made in the first place. Baxdrostat’s Phase 2a SPARK trial, published in the New England Journal of Medicine in July 2025, tested the drug in 15 patients with confirmed primary aldosteronism and produced striking results: a roughly 25 mmHg reduction in systolic blood pressure, with 73 percent of patients reaching a target below 140/90 mmHg, and a 97 percent median reduction in aldosterone levels. Those reductions surpassed what is typically achieved by adrenalectomy — surgical removal of the affected adrenal gland — which has been the definitive treatment for unilateral PA. The Phase 3 BaxHTN trial, conducted in a broader population of patients with hard-to-control hypertension, showed systolic reductions of 14.5 to 15.7 mmHg compared to 5.8 mmHg with placebo, meeting all primary and secondary endpoints.
The FDA has accepted baxdrostat’s new drug application under Priority Review, with a target action date in the second quarter of 2026. Lorundrostat’s Phase 3 Launch-HTN trial is the largest aldosterone synthase inhibitor trial completed to date, enrolling 1,083 participants with uncontrolled or resistant hypertension. Published in JAMA and recognized in that journal’s inaugural “Research of the Year” roundup, the trial showed that lorundrostat 50 mg daily achieved a 16.9 mmHg systolic reduction at six weeks and 19.0 mmHg at twelve weeks. Mineralys has announced plans to file its new drug application with the FDA in the Q4 2025 to Q1 2026 window. The key tradeoff between the two drugs will become clearer as additional safety and efficacy data emerge, but for now, both appear to represent a genuine advance over the current standard of care. One important caveat: long-term safety data beyond the trial periods is not yet available for either drug, and post-marketing surveillance will be critical for understanding their full risk profiles.
Why Spironolactone Falls Short and What the New Drugs Fix
The current mainstay treatment for primary aldosteronism, when surgery is not an option, is spironolactone — a decades-old mineralocorticoid receptor antagonist that blocks aldosterone’s effects at the receptor level. Spironolactone does work for many patients, and it remains an important medication. But it comes with a well-documented side effect profile that limits its tolerability, particularly in men. Gynecomastia, breast tenderness, and sexual dysfunction are common enough that a significant percentage of patients either refuse the medication, take it at subtherapeutic doses, or discontinue it within months of starting. The fundamental limitation of spironolactone is that it does not reduce aldosterone production. It blocks one of aldosterone’s downstream receptors while the adrenal glands continue to pour out excess hormone.
This means aldosterone-mediated damage through receptor-independent pathways may continue, and the body’s feedback mechanisms respond to the receptor blockade by further increasing aldosterone production, which can partially overcome the drug’s effect. The new aldosterone synthase inhibitors address this problem at its root by preventing the enzyme CYP11B2 from producing aldosterone in the first place. The result, as seen in the SPARK trial’s 97 percent reduction in aldosterone levels, is a more physiologically complete correction of the underlying hormonal excess. A warning is warranted here: these new drugs are not yet approved, and patients currently on spironolactone or eplerenone for diagnosed primary aldosteronism should not discontinue their medications in anticipation of a switch. The FDA review process exists for good reason, and even after approval, there will be questions about which patient populations benefit most, optimal dosing, drug interactions, and rare adverse effects that only become apparent in larger populations over longer time frames. The transition from current therapy to aldosterone synthase inhibitors, when it comes, should be guided by a physician with expertise in the condition.
What Caregivers and Families Should Watch For
For families managing a loved one’s dementia care or cognitive decline, there is a practical takeaway from the primary aldosteronism story. If the person you are caring for has a history of hypertension that has been difficult to control — particularly if they are on three or more blood pressure medications without reaching target — it is worth asking their physician whether they have ever been screened for primary aldosteronism. The screening test is a simple blood draw, and a positive result could redirect treatment in a way that meaningfully protects remaining cognitive function by addressing the vascular damage driving progression.
This is especially relevant for patients who also have atrial fibrillation, unexplained low potassium levels, or a history of early cardiovascular events. These are all clinical clues that raise the probability of underlying PA, and they should prompt a conversation with the treating physician about whether the aldosterone-renin ratio has ever been checked. Given that only 2 percent of eligible patients are currently screened, the odds are high that it has not been.
What Comes Next for Primary Aldosteronism Treatment
The convergence of updated screening guidelines and a new drug class in late-stage development creates a realistic possibility that primary aldosteronism management will look fundamentally different within the next two to three years. If either baxdrostat or lorundrostat receives FDA approval — and the trial data suggests at least one will — clinicians will have a targeted, mechanism-based therapy to offer the millions of patients whose hypertension is driven by excess aldosterone. Combined with broader screening, this could finally close the gap between how common the condition is and how rarely it is properly treated.
The larger lesson from the primary aldosteronism story is that “treatment-resistant” does not always mean the disease is resistant to treatment. Sometimes it means the disease has been misidentified, and the treatments being used are aimed at the wrong target. For the estimated 40 million Americans living with undiagnosed PA, the real resistance has not been in their biology — it has been in a medical system that was not looking for the right answer.
Conclusion
Primary aldosteronism is among the most common and most overlooked causes of hypertension in the world, affecting an estimated 40 million Americans while remaining undiagnosed in up to 95 percent of cases. The 2025 Endocrine Society guideline calling for universal screening of hypertensive patients marks a long-overdue acknowledgment of the problem’s scale, and two new aldosterone synthase inhibitors — baxdrostat and lorundrostat — are poised to offer the first targeted pharmacological alternative to surgery and the side-effect-prone spironolactone. For anyone managing their own blood pressure or caring for a family member with hard-to-control hypertension, the most important step right now is simple: ask whether primary aldosteronism has been ruled out.
A morning blood test measuring aldosterone and renin could be the difference between years of ineffective treatment and a clear path to blood pressure control and reduced risk of stroke, heart failure, and cognitive decline. The science has finally caught up to the problem. The remaining challenge is making sure the medical system catches up to the science.
Frequently Asked Questions
What is primary aldosteronism and how common is it?
Primary aldosteronism is a condition in which the adrenal glands produce excessive amounts of the hormone aldosterone, leading to high blood pressure and low potassium. Recent estimates suggest it affects approximately 40 million American adults — roughly 1 in 8 — making it far more common than previously believed. It is found in 5 to 14 percent of all hypertension patients and 20 to 30 percent of those with treatment-resistant hypertension.
How is primary aldosteronism diagnosed?
The initial screening test involves a morning blood draw, taken while seated, measuring serum aldosterone and plasma renin activity. The ratio between these two values is the primary screening tool. A concurrent potassium measurement is also taken. If the screen is positive, confirmatory testing and imaging are typically performed under the guidance of an endocrinologist.
What are baxdrostat and lorundrostat?
Both are aldosterone synthase inhibitors — a new class of drugs that block the enzyme CYP11B2, which produces aldosterone. Unlike spironolactone, which blocks aldosterone at its receptor, these drugs prevent the hormone from being made. Baxdrostat is developed by AstraZeneca and has an FDA target action date in Q2 2026. Lorundrostat is developed by Mineralys Therapeutics with an NDA filing planned between Q4 2025 and Q1 2026.
Can primary aldosteronism cause dementia or cognitive decline?
Primary aldosteronism drives chronic uncontrolled hypertension and vascular damage, both of which are established risk factors for vascular dementia and contribute to Alzheimer’s disease progression. PA also increases the risk of atrial fibrillation, which independently raises stroke risk and can lead to cerebral hypoperfusion. Identifying and treating PA may help protect cognitive function by addressing these vascular mechanisms.
Why is spironolactone not sufficient for treating primary aldosteronism?
While spironolactone effectively blocks aldosterone at its receptor, it does not reduce aldosterone production. Excess aldosterone may continue to cause tissue damage through receptor-independent pathways. Additionally, spironolactone causes significant side effects in many patients, including gynecomastia, breast pain, and sexual dysfunction, leading to poor adherence and frequent discontinuation.
Should I ask my doctor about primary aldosteronism screening?
If you have hypertension that requires three or more medications, blood pressure that remains above target despite treatment, unexplained low potassium, atrial fibrillation, or a family history of early stroke or heart disease, screening is strongly warranted. The 2025 Endocrine Society guideline now recommends screening for all hypertensive patients, though adoption of this recommendation is still in its early stages.
