Time to Drop Confirmatory Testing for Primary Aldosteronism?

Endocrinology
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General Endocrinology

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The extra test didn’t affect treatment outcomes, study suggests

by
Kristen Monaco, Senior Staff Writer, MedPage Today
May 5, 2025 • 4 min read

Last Updated
May 6, 2025 • 4 min read

The seated saline suppression test couldn’t discriminate between patients with suspected primary aldosteronism who would and would not respond to treatment.Most patients responded to treatment, and responders tended to have more severe disease manifestations at baseline.Requiring extra testing could pose a barrier to diagnosis and treatment.

A confirmatory test to verify a primary aldosteronism diagnosis had little clinical value, according to the results of an accuracy study.

Among 156 adults with a positive screening result for primary aldosteronism, the seated saline suppression test (SSST) couldn’t discriminate between patients who would or would not respond to treatment (area under the curve 62.1%, 95% CI 45.1-79.1), reported Alexander A. Leung, MD, MPH, of the University of Calgary in Canada, and colleagues in Annals of Internal Medicine.

The SSST — one of the most common confirmatory tests for primary aldosteronism — was no better than chance at predicting which patients with high-risk features responded to treatment and didn’t add any useful information, Leung told MedPage Today.

These findings may come as a surprise to many, said Leung. “For decades, doctors have relied on confirmatory tests, such as the seated saline suppression test, to diagnose primary aldosteronism.”

“It appears that confirmatory testing may be a barrier at best and misleading at worst,” he added. “Current guideline recommendations for routine confirmatory testing in primary aldosteronism may need revision.”

Removing confirmatory testing from the diagnostic-care pathway for primary aldosteronism may also help break down barriers so that clinicians can help patients quickly access appropriate treatments, he suggested. Primary aldosteronism accounts for up to 30% of all hypertension cases across the globe, but Leung’s group previously found that less than 1% of Canadian patients were diagnosed and treated.

“This is a major problem because disease-specific treatments for primary aldosteronism are highly effective and can prevent heart disease, kidney injury, and premature death,” Leung said. “One of the main barriers to care is the complexity of the recommended diagnostic tests. In particular, the historical requirement that confirmatory tests be used to secure a diagnosis of primary aldosteronism before treatment likely poses an unnecessary barrier to care. The removal of confirmatory testing as a requirement for diagnosis is a big step forward for many patients.”

The current diagnostic pathway is “lengthy, resource-intensive, and costly,” the researchers noted. It starts with screening using an aldosterone-renin ratio (ARR), which is followed by confirmatory testing in patients who screen positive and subtyping with adrenal vein sampling in those with a confirmed diagnosis, and ends with targeted treatment.

In an accompanying editorial, Jordana B. Cohen, MD, MSCE, of the University of Pennsylvania in Philadelphia, pointed out that “guidelines continue to recommend confirmatory testing with either oral sodium loading, saline infusion, fludrocortisone suppression, or captopril challenge in many patients, despite a dearth of high-quality evidence for or against this practice.”

Leung suggested that when patients have “high-probability” features of primary aldosteronism like high blood pressure, low potassium, an elevated ARR, and an adrenal nodule, a diagnosis of primary aldosteronism “should be strongly considered,” as most will respond to targeted therapy.

When available, he added that adrenal vein sampling should be considered even without a preceding confirmatory test. If it’s not available or the patient doesn’t want surgery, medical therapy with an aldosterone antagonist can be offered right away, he said.

“Further research is needed to develop and validate new ways to identify which patients would benefit most from adrenal vein sampling when surgery is being considered,” Leung suggested. “Such approaches will unlikely involve traditional confirmatory tests. Rather, the focus will likely shift to factors that predict the best surgical outcomes.”

Patients in the study were seen at a Canadian clinic from January 2017 to August 2024. All were suspected to have primary aldosteronism based on clinical features. Mean age was 53.4, and 52.6% were men.

Of these patients, 73.7% had hypokalemia, 59.6% had at least one adrenal adenoma, and 29.5% had resistant hypertension — all high-probability features of the condition.

“According to clinical practice guidelines, this type of patient would benefit most from confirmatory testing,” the researchers noted.

SSST was then performed by infusing 2 L of 0.9% sodium chloride intravenously over 4 hours with the participant seated. Blood was collected at baseline and immediately after the infusion.

“The traditional rationale for the SSST is that primary aldosteronism is a condition characterized by relative autonomous aldosterone production that is theoretically nonsuppressible with sodium loading,” Leung and team explained. “Therefore, a persistently elevated aldosterone level after volume expansion is purported to be diagnostic of primary aldosteronism.”

After confirmatory testing, patients were offered subtyping with adrenal vein sampling and disease-targeted treatment; 57.1% underwent surgery and 42.9% received targeted medical therapy. Most (91%) responded to treatment; responders tended to have more severe disease manifestations at baseline.

When measured using an immunoassay, there was a large overlap in saline-suppressed aldosterone concentrations for patients who responded to treatment (median 329 pmol/L; range 104-1,370) and those who did not (median 255 pmol/L; range 50-828). There was also a great deal of overlap when using liquid chromatography-tandem mass spectrometry for treatment responders (median 203 pmol/L; range 27-1,130) and nonresponders (median 106 pmol/L; range 10-506).

Performance of the SSST was similar when the group was restricted to just patients who underwent surgery, and when certain groups were excluded, including those with a history of spontaneous hypokalemia, direct renin concentration less than 1.0 mIU/L, and plasma aldosterone concentration greater than 555 pmol/L.

Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was supported by the Canadian Institutes of Health Research, the Hypertension Canada New Investigator Award, the Heart and Stroke Foundation of Canada’s National New Investigator Award, the Kidney Foundation of Canada, and the Lorna Jocelyn Wood Chair for Kidney Research.

Leung reported relationships with the Canadian Institutes of Health Research and Hypertension Canada. Co-authors reported relationships with the American Association for Clinical Chemistry, MSACL.org, Roche Diagnostics GmbH, Siemens Healthcare, Novo Nordisk, Canadian Institutes of Health Research, Kidney Foundation of Canada, Endocrine Society, and Boston Scientific.

Cohen reported no disclosures.

Primary Source

Annals of Internal Medicine

Source Reference: Leung AA, et al “Confirmatory testing for primary aldosteronism: a study of diagnostic test accuracy” Ann Intern Med 2025; DOI: 10.7326/ANNALS-24-03153.

Secondary Source

Annals of Internal Medicine

Source Reference: Cohen JB “Rethinking confirmatory testing in primary aldosteronism” Ann Intern Med 2025; DOI: 10.7326/ANNALS-25-01368.