From Hidden Diagnosis to Targeted Treatment: Primary Aldosteronism Essentials for Pharmacists

Introduction and Background

Despite being one of the most common and treatable causes of secondary hypertension, primary aldosteronism (PA) remains underrecognized in clinical practice. Updated guidelines now call for broader screening, making pharmacist awareness of red flags and appropriate screening, monitoring, and treatment recommendations more critical than ever.

PA is characterized by renin-independent aldosterone secretion, which drives sodium reabsorption in the kidneys, water retention, and increased blood pressure. Under normal conditions, aldosterone is regulated by the renin-angiotensin-aldosterone system, but with uncontrolled aldosterone production comes increased sodium reabsorption and renal potassium wasting, leading to hypertension and often hypokalemia. Although it was previously thought to be a rare condition, PA is now recognized as the leading cause of secondary hypertension and a driver of cardiovascular risk. PA affects around 20% of patients with resistant hypertension, 10% with severe hypertension, and 6% with uncomplicated hypertension.¹

PA can be categorized as either an aldosterone-producing adenoma (APA) or bilateral hyperaldosteronism (BHA).¹ In APA, excess aldosterone is produced from either the right or left adrenal gland, whereas in BHA, both adrenal glands are involved.^1,2 BHA is more common, accounting for about 60% of cases.³ Rarer subtypes of PA also exist, such as familial hyperaldosteronism types I through IV, which account for 1% to 5% of cases.³

The clinical presentation of PA can vary, making diagnosis and detection more challenging. Previously, treatment-resistant hypertension and hypokalemia were considered important markers of possible PA. Evidence confirms that PA can be present without these indicators, making all patients with hypertension candidates for screening.⁴ PA contributes to kidney disease, heart failure, atrial fibrillation, coronary artery disease, and stroke; early detection and treatment are imperative.³

Guideline Updates

The Endocrine Society first published clinical practice guidelines on PA in 2016, intending to provide recommendations for prevention and management.⁵ The initial guidelines recommended screening high-risk patients for PA using the plasma aldosterone-renin ratio (ARR). High-risk groups included those with moderate to severe hypertension or resistant hypertension, hypertension with obstructive sleep apnea, an adrenal incidentaloma, or spontaneous/diuretic-induced hypokalemia.⁵ Recent data suggest that PA is more prevalent than previously estimated, rising from affecting just over 5% of individuals with hypertension to nearly 20%.¹

In response, updated clinical practice guidelines were released in September 2025.^5,6 The new guideline recommendations emphasize that all patients with hypertension should be screened for PA by measurement of serum aldosterone, plasma renin, and potassium levels to calculate and interpret the ARR.⁶ The cutoff value for ARR is 30 ng/dL, meaning that PA is suspected when the result is higher than 30, but a result below 30 is considered normal.⁷ This shift greatly expands the population eligible for testing, as almost half of the US population is estimated to have hypertension.⁸ Pharmacists in all practice settings may be involved in treating patients with hypertension and are vital in ensuring PA screening aligns with current recommendations.

The 2016 guidelines provided an algorithm for screening and confirmatory testing for PA; the updated guidelines have elaborated on the differences between PA subtypes and the management of PA in patients with hypertension, refining the diagnostic and treatment pathways. The updated guidelines also discuss the use of a dexamethasone suppression test in patients who present with adrenal adenomas to identify lateralization of the aldosterone secretion and exclude other possible diagnoses, such as Cushing syndrome. For patients with lateralizing or unilateral aldosterone production, adrenalectomy remains the preferred treatment approach. For those with contraindications to surgery or who do not wish to undergo surgery, an alternative option is treatment with a mineralocorticoid receptor antagonist (MRA). The guidelines emphasize that shared decision-making should be used in conjunction with the algorithms to determine the most appropriate next steps for individual patients who have PA.^5,6

Medical Therapy and Monitoring

Patients who do not have surgery require lifelong therapy and should be treated with an MRA. Although the recommendation states that MRAs can be used and may have a similar efficacy when titrated to parallel potencies, spironolactone is often listed as the preferred MRA. Although the data are limited, spironolactone had better blood pressure-lowering effects, wider availability, lower costs, and fewer adverse effects (AEs) compared with other MRAs.⁶

When initiating and adjusting MRA therapy, pharmacists should consider the overall treatment regimen, including whether to discontinue other antihypertensives and assess the severity of hypertension. The 2025 guidelines recommend titration if blood pressure remains uncontrolled and the renin level is suppressed, with the aim of seeing an increase in renin from baseline. This is not a strict recommendation due to inconsistent effectiveness and the absence of a defined target renin level. Pharmacists also play a key role in monitoring renal function, potassium and renin levels, and blood pressure, especially following the initiation of therapy. Potassium levels typically normalize within a few days of beginning MRA therapy; therefore, potassium supplementation will likely need to be discontinued shortly after initiation. More frequent monitoring of serum potassium levels is warranted for patients with persistent hypokalemia or those requiring chronic supplementation.^5,6 A summary of spironolactone dosing strategies, monitoring intervals, and counseling pearls is provided in the Table.⁶

The Role of the Pharmacist

Pharmacists practicing in primary care, community, or hospital settings may all encounter patients with hypertension and can play a role in suggesting screening for PA when appropriate. As pharmacists are often on the front line of patient interactions, they are well positioned to support and initiate discussions about screening in line with the updated recommendations. The guideline recommends that all patients with hypertension undergo at least 1 screening for PA. Repeat screening is not routine but may be considered if clinical features change, such as the development of hypokalemia or worsening blood pressure. Once PA is diagnosed, pharmacists can help ensure therapy is optimized. The guidelines emphasize that MRAs are the agents of choice over nonspecific antihypertensive agents. Pharmacists’ understanding of MRA pharmacology, dosing, titration, monitoring, and AEs is essential for ensuring medication safety and efficacy.⁶ This includes recognizing when potassium supplementation should be discontinued, monitoring laboratory values such as potassium and renal function, and adjusting other antihypertensives.

Beyond direct medication management, pharmacists can also contribute by supporting adherence, identifying and managing drug interactions, counseling patients about AEs, and collaborating with prescribers to streamline care. Untreated PA critically increases the risk for renal dysfunction, left ventricular hypertrophy, atrial fibrillation, and stroke, but with guideline-directed screening and treatment, pharmacists can help reduce these risks.³ The updated guidelines also clarify the diagnostic pathway and treatment algorithm.⁶ Here, pharmacists embedded in clinical practice can help streamline clinical workflows and reduce unnecessary treatment delays. By applying the 2025 guideline updates in practice, pharmacists can proactively identify and manage this underdiagnosed condition, ensure appropriate treatment, and improve long-term outcomes.

REFERENCES

1. Byrd JB, Turcu AF, Auchus RJ. Primary aldosteronism: practical approach to diagnosis and management. Circulation. 2018;138(8):823‑835. doi:10.1161/CIRCULATIONAHA.118.033597

2. Amar L, Plouin PF, Steichen O. Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism. Orphanet J Rare Dis. 2010;5:9. doi:10.1186/1750-1172-5-9

3. Nanba K, Rainey WE. Pathophysiology of bilateral hyperaldosteronism. Curr Opin Endocrinol Diabetes Obes. 2022;29(3):233-242. doi:10.1097/MED.0000000000000729

4. Vedere T, Khalifa M. Primary hyperaldosteronism: a comprehensive review of pathophysiology, diagnosis, and treatment. Urol Clin North Am. 2025;52(2):205-216. doi:10.1016/j.ucl.2025.01.003

5. Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061

6. Adler GK, Stowasser M, Correa RR, et al. Primary aldosteronism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2025;110(9):2453-2495. doi:10.1210/clinem/dgaf284

7. Step 1: Aldosterone renin ratio (ARR). Primary Aldosteronism Foundation. Accessed September 22, 2025. https://primaryaldosteronism.org/step-1-aldosterone-renin-ratio-arr/

8. Hypertension and physical activity 2024 statistics infographic. American Heart Association. January 24, 2024. Accessed September 22, 2025. https://newsroom.heart.org/file/hypertension-and-physical-activity-2024-statistics-infographic?action