Today, I review, link to, and excerpt from The Curbsiders‘ “#515 Primary Aldosteronism, A Deep Dive: Easy on the Salt!”*

*Ahmad M, Vaidya A, Williams PN, Watto MF. “#515: Easy on the Salt! A Deep Dive on Primary Aldosteronism”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast February 23, 2026.

All that follows is from the above resource.

Transcript available via YouTube

Helping you diagnose a common cause of hypertension!

Hypertension is a growing disease globally, affecting millions of individuals and increasing the risk of heart disease and stroke. Along with the expert help of Dr. Vaidya (Brigham and Women’s Hospital), we help reimagine the approach of clinicians in terms of hypertension and help them navigate common diagnostic dilemmas! @AnandVaidya17 (Bluesky) @AnandVaidya17 (X)

Claim CME for this episode at curbsiders.vcuhealth.org!

Show Segments

• Introduction and Personal Interests
• Advice and Wisdom in Medicine
• Case 1
• Defining Primary Aldosteronism
• Screening for Primary Aldosteronism
• How common is Primary Aldosteronism
• Challenges in Diagnosis and Testing
• Medication Management and Testing Protocols
• Managing indeterminate cases
• Aldosterone Suppression Testing and its role
• Discussing treatment options with patients
• Case 2
• Considering genetic causes of Primary Aldosteronism
• The need for AVS for lateralization
• Upcoming imaging modalities for Primary Aldosteronism
• Case 3
• Medical Management of Primary Aldosteronism
• Future Directions in Treatment

Primary Aldosteronism Pearls

1. Primary aldosteronism is a common cause of hypertension and screening should be considered in all hypertensive patients
2. Screening includes checking an aldosterone level, a plasma renin activity or direct renin concentration, an aldosterone renin ratio,  along with a potassium level
3. Blood pressure medications do not need to be held to screen for PA however you should know how these medicines can affect lab results
4. If PA is diagnosed treatment should be guided by whether the patient is interested in surgical management of PA or medical management
5. If surgical management is pursued a CT of the abdomen and pelvis without contrast is useful to look for an adenoma and also provides information for an interventional radiologist if adrenal venous sampling is performed
6. Just because a person does not have an adenoma does not mean they do not have lateralizing PA so AVS should always be considered in those who wish for surgical management of disease
7. When treating individuals with MRA therapy the main goals are normalizing blood pressure, stopping the need for potassium supplements, and increasing renin to a level that is above the baseline for the patient.

Primary Aldosteronism Show Notes

What is primary aldosteronism

Definition

Primary aldosteronism (PA) is a pathologic, non suppressible form of aldosterone excess which is independent of renin and angiotensin II (Vaidya et al. 2022).  Primary aldosteronism is not a binary disease but rather exists on a spectrum with some patients having mild disease while others have more severe forms of disease. The etiology of disease is typically due to somatic mutations which can increase in number with time (Vaidya et al. 2022).

Prevalence

Previously, PA was thought to be a rare cause of hypertension, however, growing evidence suggests that it is much more common than previously thought (Rossi et al. 2024, Vaidya et al. 2022). Some studies estimate the prevalence to be 10-25% of all patients with hypertension (Rossi et al. 2024, Vaidya et al. 2022). Despite these high estimated rates of PA, the screening rates are still abysmally low. It is estimated that less than 1% of patients with PA are actually diagnosed (Vaidya et al. 2022). Factors that contribute to these low rates include decreased awareness regarding its prevalence, assuming that patients with PA often have hypokalemia and refractory hypertension, and using high aldosterone cutoffs to diagnose PA (Rossi et al. 2024, Vaidya et al. 2022).

Why is recognizing PA important

Primary hyperaldosteronism has been linked to multiple comorbidities including left ventricular hypertrophy, diastolic dysfunction, chronic kidney disease, stroke, coronary artery disease, type 2 diabetes, and atrial fibrillation (Dogra et al. 2023, Rossi et al. 2024, Vaidya et al. 2022). This increased risk appears to be independent of just hypertension, as studies have shown people with PA are at higher cardiovascular risk as compared to patients with hypertension in the absence of PA (Dogra et al. 2023, Rossi et al. 2024, Vaidya et al. 2022). The pathophysiology behind these risks is thought to be oxidative damage caused by aldosterone, leading to inflammation, fibrosis and vascular damage (Rossi et al. 2024, Vaidya et al. 2022).

Diagnosis of PA

Who to screen

The 2025 Endocrine Society guidelines now suggest screening ALL patients with hypertension at least once for PA, whereas  prior Endocrine Society guidelines had various screening criteria that highlighted multiple groups of patients that would benefit from PA screening (Adler et al. 2025). This guidance comes from the increasing number of studies highlighting how prevalent the condition is in hypertensive patients and the fact that screening rates are extremely low. These international guidelines however do suggest screening tests should be sent based on local expertise and experience, resources and healthcare system capacity (Adler et al. 2025). As Dr. Vaidya points out in the podcast however, even if availability of adrenal venous sampling (AVS) or adrenalectomy is low, mineralocorticoid receptor antagonist (MRA) therapy has been shown to be effective in these patients and therefore should not prohibit screening for PA.

How to screen

Screening involves measurement of the aldosterone level, a plasma renin activity (PRA) or direct renin concentration (DRC), and calculation of the aldosterone renin ratio (ARR) (Adler et al. 2025). A potassium level should also be sent at the same time as these labs, as hypokalemia can lower aldosterone levels and give a false negative test. Per the guidelines, testing should take place first thing in the morning fasting, however per Dr. Vaidya, the most practical approach is to have them get blood work whenever they can. Washout of blood pressure medications is not required prior to testing (Adler et al. 2025, Dogra et al. 2023); Dr. Vaidya does not stop medications prior, and suggests only considering washout after initial testing negative and high clinical suspicion.

A positive screening test is an aldosterone concentration greater than or equal to 7.5 ng/dL via LC-MS and 10 ng/dL via immunoassay in the setting of a PRA of less than of 1 ng/ml/h  or a DRC of less than or equal to 8.2 mU/L (Adler et al. 2025). Per guidelines, the ARR should be greater than 20 if aldosterone via immunoassay/PRA is used or greater than 15 if aldosterone via LC-MS/PRA is used (Adler et al. 2025). Of note, just because screening was performed and was negative once does not mean it should not be repeated. A study by Yozamp at al. demonstrated there is intraindividual variation in aldosterone and renin concentrations and ratios on a day-to-day basis, and if you have a high suspicion you should retest (Yozamp et al. 2020).

Interpreting tests with medications

Although it is not recommended to hold antihypertensive medications for initial screening for PA, one must recognize the effect they can have on the interpretation of lab results. False negatives are far more common than false positives when it comes to testing (Vaidya et al. 2022). Medications that can cause false negative results include diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), dihydropyridine calcium channel blockers, mineralocorticoid receptor antagonists (MRAs), and ENaC inhibitors (Adler et al. 2025). If you suspect that one of these medications is causing a false negative test, you can consider replacing it with a non-interfering medication and retesting the patient (Adler et al. 2025). Dr. Vaidya points out that ACE inhibitors or ARBs raise renin, so low renin levels in the setting of even “normal” aldosterone levels should make one suspicious of PA.

In terms of medications that can cause false positives, these include beta blockers and alpha 2 agonists such as clonidine and alpha methyldopa (Adler et al. 2025). The guidelines do note however if a patient is on beta blockers or alpha 2 agonists and noted to have an aldosterone level of greater than or equal to 10 ng/dL by immunoassay or 7.5 ng/dL by LC-MS, the likelihood of a false positive test is low and PA is likely (Adler et al. 2025).

If washing out is required for retesting, it is recommended to wash out MRAs and ENaC inhibitors for 4 weeks and other interfering medications for 2 weeks (Adler et al. 2025). Examples of medications one can consider during the washout period that do not affect renin or aldosterone concentrations include hydralazine, alpha 1 adrenergic antagonists, and nondihydropyridine calcium channel blockers (verapamil and diltiazem) (Dogra et al. 2023).

Aldosterone Suppression Testing

In the latest Endocrine Society guidelines, experts do not suggest additional suppression or stimulation testing for all patients, however they do suggest aldosterone suppression testing when there is an intermediate probability for lateralizing PA and interest in potential surgical intervention (Adler et al. 2025). This recommendation notably has a very low level of certainty and there is debate surrounding the utility(Adler et al. 2025). In terms of its use in diagnosing PA, studies have shown they are not as accurate as once previously thought. A recent study by Leung et al. at the University of Calgary demonstrated the saline suppression test was unable to discern between patients with and without PA who could benefit from specific, aldosterone directed therapies (Yeung et al. 2025)

Even more recently, Dr. Vaidya was part of a study comparing the discordance and shortcomings of multiple aldosterone suppression tests among patients with high probability features of PA and found significant discordance amongst various tests (Tsai et al. 2025). The study called into question whether or not these tests (the saline suppression test and the captopril challenge test) could be used to accurately discern whether a patient had lateralizing PA which would benefit from adrenalectomy  (Tsai et al. 2025). Per the study, 6.6% to 27.9% of patients who had lateralizing PA had a negative saline suppression test or captopril challenge test demonstrating a large portion of missed patients (Tsai et al. 2025). These studies therefore demonstrate that a diagnosis of PA should not rely on confirmatory aldosterone suppression testing. In fact, these tests may also not be a good way to tell whether a patient has lateralizing PA or not.

Treatment of PA

Medical therapy

The treatment of primary aldosteronism should be an individualized decision between the patient and the provider discussing the risks and benefits of medical management versus pursuing a surgical approach.

If the patient does not desire surgery or is not a candidate for surgery, patients should be treated with MRAs which include spironolactone and eplerenone (Adler et al. 2025). Dr. Vaidya tends to start with the lowest dose of spironolactone (12.5 mg daily) and adjusts other blood pressure medications if necessary. In men, he utilizes eplerenone due to the significant gynecomastia and sexual dysfunction that can occur with spironolactone. It should be noted however eplerenone often requires higher dosing than spironolactone and is typically dosed twice daily (Weinberger et al. 2002). The goals of therapy include normalizing blood pressure (Dr. Vaidya emphasizes this is the top priority), normalizing potassium levels and weaning patients off of potassium supplements, and achieving a non-suppressed renin level (Adler et al. 2025).

After starting patients on MRA therapy, the guidelines suggest following up in 2-3 months or sooner if necessary and monitoring blood pressure, potassium, renin, and renal function (Adler et al. 2025). If the patient’s blood pressure is still elevated in the setting of a low renin, the guidelines recommend increasing the dose of MRA (Adler et al. 2025). If the blood pressure is uncontrolled despite a nonsuppressed renin level, the guidelines suggest adding or increasing the dose of a non-MRA antihypertensive medication (Adler et al. 2025). If blood pressure is controlled and the renin remains suppressed, the MRA should be increased and other non-MRA antihypertensive medication doses should be decreased (Adler et al. 2025).

Surgical therapy

If a patient is interested in adrenalectomy to treat their PA, per Dr. Vaidya a CT of the abdomen and pelvis without contrast is useful to identify the very rare adrenal carcinomas that can present with PA and also to serve as a map for interventional radiologists prior to adrenal venous sampling (AVS). AVS is necessary in all patients with PA despite the presence or absence of nodules noted on CT scan, as oftentimes aldosterone producing microadenomas and bilateral lesions are not noted on CT or MRI (Rossi et al. 2013, Rossi et al. 2025). ACTH stimulation can be used during AVS due to fluctuations in cortisol levels that can occur due to the stress of the procedure (Naruse et al. 2021). This stress can affect the selectivity index (the measure that confirms successful cannulation) and the lateralization index (the measure that confirms which adrenal gland is making more aldosterone) (Naruse et al. 2021). There have been studies both in favor of or opposing the use of ACTH stimulation as it is suspected that some PA adenomas have higher melanocortin 2 receptors (ACTH receptors) which may benefit more from ACTH stimulation for lateralization(Naruse et al. 2021). The Endocrine Society Guidelines do suggest however that patients who are younger with overt PA disease and a unilateral adenoma may not need AVS testing (Adler et al. 2025). This recommendation was made due to the fact that adrenal lesions in this age group are rare and are more likely to be functional. A multicenter study conducted by Rossi et al. noted that in patients aged less than 45 years with PA, CT was able to accurately identify a unilateral nodule in young patients with hypokalemia as the source of aldosterone production 100% of the time, however, in patients without hypokalemia it was only 88% accurate (Rossi et al. 2021).

Future directions

PA is a rapidly evolving space with studies currently ongoing in the treatment and diagnosis of disease. Aldosterone synthase inhibitors are currently being developed and have shown promise in improving blood pressure in the space of PA (Mulatero et al. 2024, Turcu et al. 2025). These are also being researched in the field of chronic kidney disease and resistant hypertension as well as potential agents that may be crucial in hypertension management in the near future (Park 2025, Tuttle et al. 2024). In addition to major strides being made in terms of treatment of PA, multiple imaging modalities are being studied to help lateralize PA without the need for AVS. These include metomidate PET-CT and aldosterone synthase specific F-labeled radioligand for PET scanning (Ragnarsson et al. 2025, Teo et al. 2025) . In the near future these imaging modalities may help decrease the need for AVS when lateralizing for PA.