Primary aldosteronism sits at the crossroads of endocrinology, hypertension, and cardiovascular prevention. It is now recognized as the most common endocrine cause of secondary hypertension, yet it remains profoundly underdiagnosed. The 2025 Clinical Practice Guideline from the Endocrine Society, supported by a comprehensive systematic review, adds important numerical clarity to long suspected clinical patterns and strengthens the case for earlier, more targeted care.
Why Primary Aldosteronism Deserves More Attention
Population data show that primary aldosteronism affects 5–14% of all patients with hypertension in general practice. In referral centers and resistant hypertension clinics, prevalence rises to 20–30%. Despite this, up to 95% of cases remain undiagnosed, often for many years.
That delay has consequences. Compared with patients who have essential hypertension at similar blood pressure levels, those with untreated primary aldosteronism face:
- Afib: Approximately 2-fold higher rates of atrial fibrillation
- Stroke: 1.5–2-fold higher risk of stroke
- HF, CKD, Mortality: Higher rates of heart failure, chronic kidney disease, and overall mortality
These risks persist even when office blood pressure appears “controlled,” highlighting that aldosterone causes direct tissue injury beyond hemodynamic effects.
Screening: Move Earlier, Not Later
The guideline reinforces broader screening using the aldosterone to renin ratio, a low-cost blood test that identifies over 90% of cases when properly performed. Yet real-world data show that fewer than 5% of eligible hypertensive patients ever receive this test.
One large observational study of over 260,000 patients demonstrated that individuals who underwent screening were significantly more likely to receive aldosterone-specific therapy and achieved sustained systolic blood pressure reductions of 5–7 mmHg over time compared with unscreened peers.
Importantly, the guideline cautions against relying on potassium levels alone. Across studies, more than 50% of patients with confirmed primary aldosteronism had normal serum potassium at diagnosis.
Diagnosis: Precision Over Assumptions
After a positive screen, confirmatory testing and subtype classification determine management. The updated evidence provides clearer numbers to guide decisions.
Imaging vs Adrenal Venous Sampling
- Computed tomography identifies adrenal nodules but misclassifies disease laterality in a substantial fraction of cases. Across pooled studies involving more than 13,000 patients, CT alone failed to correctly identify unilateral disease in up to 30–40% of cases.
- Adrenal venous sampling improves biochemical cure rates after surgery. Patients selected for adrenalectomy using adrenal venous sampling achieved complete biochemical cure more often than those selected by CT alone, with odds ratios favoring adrenal venous sampling despite a small increase in procedural risk. Adrenal hemorrhage occurred in well under 1% of procedures in experienced centers.
Treatment: Target Aldosterone, Not Just Blood Pressure
A central message of the guideline is the importance of treatment specificity, focusing on the root cause of disease. Lowering blood pressure without addressing aldosterone excess leaves residual risk.
1. Surgery vs Medical Therapy
Across more than 18,000 patients in pooled analyses, adrenalectomy for unilateral disease consistently outperformed medical therapy. Compared with mineralocorticoid receptor antagonists, surgery was associated with:
- Systolic BP: ~5 mmHg lower systolic blood pressure
- Medications: 1–1.5 fewer antihypertensive medications
- BP Control: ~50% lower odds of achieving poor blood pressure control
- Mortality: ~2-fold lower all-cause mortality in long-term follow-up
- Stroke: Its risk was also significantly lower after surgery, with odds ratios approaching 0.55 in some analyses.
Medical therapy remains essential for bilateral disease or when surgery is not appropriate, but outcomes depend heavily on dosing adequacy.
2. Choosing the Right Mineralocorticoid Receptor Antagonist
Spironolactone demonstrated superior potassium control compared with eplerenone in head-to-head studies, with mean potassium differences of approximately 0.2 mmol/L favoring spironolactone. Patients treated with eplerenone required, on average, one additional antihypertensive medication to achieve similar blood pressure targets.
Androgen-related side effects occurred in 10–20% of men treated with spironolactone, most commonly gynecomastia or breast tenderness. Dose reduction resolved symptoms in many cases.
Emerging data on finerenone suggest comparable blood pressure and potassium control with fewer sex hormone-related effects, though long-term outcomes remain under study.
Renin as a Treatment Signal
One of the most clinically impactful updates involves renin monitoring. Persistent renin suppression during medical therapy is not benign.
Across several observational cohorts totaling nearly 4,000 patients, suppressed renin during treatment was associated with:
- Stroke: 3–5-fold higher stroke risk
- Afib: 2–3-fold higher atrial fibrillation risk
- Mortality: Significantly higher all-cause mortality
In contrast, patients whose renin became unsuppressed showed better potassium control and fewer cardiovascular events, even when blood pressure differences appeared modest. This finding reframes treatment goals and supports titration beyond symptom-based targets.
Summary Table: What the Guideline Emphasizes
| Care Area | Updated Guidance | Key Numbers |
|---|---|---|
| Screening | Broader ARR testing | Detects >90% of cases |
| Missed diagnosis | Common in practice | ~95% underdiagnosed |
| CT alone | Limited accuracy | 30–40% misclassification |
| Surgery | Preferred for unilateral PA | ~2× lower mortality |
| Medical therapy | Use MRAs | BP ↓ ~5 mmHg when optimized |
| Renin monitoring | Avoid suppression | Stroke risk ↑ 3–5× if suppressed |
Patient Scenarios That Reflect Real Practice
- Case 1 — Resistant Hypertension: A 52-year-old man on four agents shows systolic pressures near 155 mmHg. Targeted therapy lowers readings by ~15 mmHg within months.
- Case 2 — Normal Potassium Trap: A 45-year-old woman with atrial fibrillation and potassium 4.1 mmol/L still meets biochemical criteria for primary aldosteronism.
- Case 3 — Surgical Resolution: A 38-year-old patient discontinues three medications after adrenalectomy and maintains pressures near 120/75.
- Case 4 — Renin Guided Therapy: A 61-year-old with bilateral disease improves only after spironolactone titration raises renin into the measurable range.
- Case 5 — Side Effect Navigation: A patient transitions from spironolactone to eplerenone after breast tenderness, maintaining control with adjusted dosing.
A Broader Clinical Perspective
The guideline openly acknowledges that much of the evidence remains low to very low certainty. Still, the direction of effect remains remarkably consistent across decades of data. Aldosterone excess drives cardiovascular harm independent of blood pressure. Targeted treatment reduces that harm. Precision, not intensity alone, defines success.
Key Takeaway
Primary aldosteronism is common, measurable, and treatable. The 2025 Endocrine Society update adds numerical weight to a long-standing message. Earlier screening, aldosterone-specific therapy, and renin-aware titration can meaningfully reduce stroke, heart failure, and premature death.
At our practice in Montgomery County, Maryland, and through virtual care, we apply these updated principles to deliver individualized, comprehensive endocrine and hypertension care that focuses on physiology, outcomes, and long-term risk reduction.
References:
- Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology and Metabolism. 2025. Adler GK, Stowasser M, Correa RR, et al.Guideline
- A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline on Management of Primary Aldosteronism. The Journal of Clinical Endocrinology and Metabolism. 2025. Farah MH, Hegazi M, Firwana M, et al.
- Nationwide, Pragmatic, Direct-to-Patient Primary Aldosteronism Testing Program. Hypertension. 2025. Brown JM, Tsai LC, Abel EE, et al.
About Dr. Gerti Tashko, MD
Dr. Gerti Tashko, MD, is an endocrinologist in Montgomery County, Maryland. He is uniquely quadruple board-certified in endocrinology, lipidology, hypertension, and obesity medicine. His practice delivers root-cause-focused metabolic and endocrine care, available virtually and in person. He uses advanced diagnostics, personalized nutrition, and preventive medicine to improve long-term health.
