Michael Monostra , 2025-05-08 13:13:00
Key takeaways:
- A seated saline suppression test had a high false-negative rate for predicting response to primary aldosteronism therapy.
- Novel tools are needed to better predict who may benefit most from adrenal vein sampling.
Confirmatory tests are poor at predicting which patients may respond to treatment for primary aldosteronism, researchers reported in a study published in Annals of Internal Medicine.
“For decades, doctors have relied on confirmatory tests, such as the seated saline suppression test, to diagnose primary aldosteronism and to guide treatment decisions,” Alexander Leung, MD, MPH, associate professor in the departments of medicine and community health sciences at the University of Calgary Cumming School of Medicine in Alberta, Canada, told Healio. “However, it may be surprising to some that the evidence base for such testing is weak. The current study extends previous work and shows that confirmatory tests for primary aldosteronism are simply not reliable and should not be used to decide on which patients should be treated.”
Leung and colleagues assessed data from 156 adults with hypertension and an elevated aldosterone-renin ratio who were suspected of having primary aldosteronism and open to considering surgical treatment (mean age, 53.4 years; 52.6% men). A seated saline suppression test was performed in all participants. Aldosterone levels were measured through immunoassay and liquid chromatography-tandem mass spectrometry, with different cutoffs used for each type of aldosterone measure.
Of the study group, 57.1% underwent surgery and 42.9% were prescribed targeted drug therapy. The proportion of participants who responded to treatment was 91%.
Low accuracy with confirmatory testing
When aldosterone concentrations were measured by immunoassay, there was a large overlap between responders to treatment and nonresponders. Responders had a median aldosterone of 329 pmol/L and a range from 104 pmol/L to 1,370 pmol/L, whereas median aldosterone for nonresponders was 255 pmol/L with levels ranging from 50 pmol/L to 828 pmol/L.
A similar finding was observed for concentrations measured through liquid chromatography-tandem mass spectrometry. Responders to therapy had median aldosterone of 203 pmol/L and a level ranging from 27 pmol/L to 1,130 pmol/L. Nonresponders had a median aldosterone of 106 pmol/L, with levels ranging from 10 pmol/L to 506 pmol/L.
The seated saline suppression test performed no better than chance for determining treatment response, with an area under the curve of 62.1% for immunoassay and 62.9% for liquid chromatography-tandem mass spectrometry, with 95% confidence intervals crossing 50% for both, the researchers wrote.
Using immunoassay measures, the seated saline suppression test had a false-negative rate of 76.9% with an aldosterone cutoff of less than 140 pmol/L and an 87.7% false-negative rate for aldosterone levels less than 280 pmol/L. Liquid chromatography-tandem mass spectrometry measures had similar false negative rates.
The findings were similar in subgroup analyses examining only patients receiving surgery, those with normal serum potassium at baseline, and people with a history of spontaneous hypokalemia, renin levels of less than 1 mIU/L and aldosterone concentration of more than 555 pmol/L.
Leung said the findings indicate that confirmatory testing is an unnecessary step in the diagnostic treatment paradigm, suggesting instead that health care professionals strongly consider diagnosing primary aldosteronism in patients with clinical features of the disease, such as high blood pressure, low potassium, a high aldosterone-to-renin ratio and an adrenal nodule.
“It appears that confirmatory tests may be a barrier to care and current guideline recommendations for routine confirmatory testing in primary aldosteronism may need revision,” Leung said. “The removal of confirmatory testing as a requirement for diagnosis will be a big step forward for many patients.”
New diagnostic tools needed
In a related editorial, Jordana B. Cohen, MD, MSCE, associate professor of medicine in the renal-electrolyte and hypertension division and in the department of biostatistics, epidemiology and informatics at the University of Pennsylvania, wrote the study adds to the evidence against the use of confirmatory testing for primary aldosteronism. Leung noted most of the treatment responders in the study had more severe disease manifestations, and the accuracy of seated saline suppression testing may be worse among patients with milder disease.
“Confirmatory testing for primary aldosteronism has not been systematically demonstrated to be able to serve its intended purpose,” Cohen told Healio. “These tests have high false-negative rates, meaning that they can actually prevent many people from receiving appropriate treatment.”
Jordana B. Cohen
Cohen concluded that new tools and technologies for diagnosing primary aldosteronism are needed in place of confirmatory testing. One such tool is a novel molecular imaging test, which was deemed as an accurate alternative to adrenal vein sampling in a small trial published in Annals of Internal Medicine in March.
“[The imaging tool] could allow patients to forgo adrenal vein sampling when being evaluated as to whether surgery would be appropriate to treat their primary aldosteronism,” Cohen said.
Leung agreed with Cohen, and said more studies are needed to identify alternatives to adrenal vein sampling for identifying patients who would most benefit from surgical treatment.
“Such approaches will unlikely involve traditional confirmatory tests, such as the seated saline suppression tests,” Leung said. “Rather, the focus will likely shift to factors that predict the best surgical outcomes.”
References:
Cohen JB. Ann Intern Med. 2025;doi:10.7326/ANNALS-25-01368.
Goodchild E, et al. Ann Intern Med. 2025;doi:10.7326/ANNALS-24-00761.
For more information:
Jordana B. Cohen, MD, MSCE, can be reached at jco@pennmedicine.upenn.edu.
Alexander Leung, MD, MPH, can be reached at aacleung@ucalgary.ca.
Sources/Disclosures
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Disclosures:
Cohen and Leung report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
