medwireNews: The seated saline suppression test (SSST) has a very high false negative rate for confirming a diagnosis of primary aldosteronism (PA) in people who already have a positive screening result, Canadian study findings indicate.
Writing in the Annals of Internal Medicine, Alexander Leung (University of Calgary, Alberta) and co-authors say their “study indicates that the SSST for PA is not only of little value but also potentially harmful, suggesting that current recommendations for routine confirmatory testing in PA may need revision.”
They explain that that the diagnostic pathway for PA involves several steps, beginning with screening using an aldosterone–renin ratio (ARR), followed by confirmatory testing in patients who screen positive, and subtyping with adrenal vein sampling in those with confirmed PA. Targeted treatment includes surgery for patients with lateralizing PA, or mineralocorticoid receptor antagonist therapy in those with nonlateralizing PA.
“Opportunities to simplify this pathway would have tremendous potential to improve the efficiency of diagnosis and care,” Leung et al remark, noting that earlier research suggests that confirmatory SSST testing “adds little beyond the standard screening test in many cases.”
The blinded assessment of the SSST included 156 adults (mean age 53 years, 53% men) who had an elevated ARR and suspected PA based on clinical features including resistant hypertension. They underwent the SSST, during which 2 L of 0.9% sodium chloride was administered intravenously over 4 hours, followed by adrenal vein sampling and targeted treatment.
At 6 months, 91% of participants had a treatment response defined according to the international consensus criteria from the Primary Aldosteronism Surgery Outcome study that includes blood pressure and antihypertensive drug dose reductions, and biochemistry normalization.
The researchers report that the median post-SSST aldosterone concentration measured by immunoassay was higher among treatment responders than among nonresponders, at 329 pmol/L versus 225 pmol/L, but there was substantial overlap in the interquartile ranges, at 227 to 525 pmol/L and 162 to 346 pmol/L, respectively. There was similar overlap when aldosterone was measured by liquid chromatography–tandem mass spectrometry (LC-MS).
This meant that the SSST could not reliably discriminate between responders and nonresponders better than chance, with an area under the receiver operating characteristic curve of 62.1% for the immunoassay and 62.9% for LC-MS.
The SSST also had low specificity (21.4–57.1%) across all possible plasma aldosterone concentration cut-offs (140–300 pmol/L) and high false negative rates (76.9–89.0%) when using the immunoassay, and a similarly high false negative rate was observed for LC-MS.
Furthermore, the positive and negative likelihood ratios were equivocal, with point estimates close to 1 or confidence intervals crossing 1, for all aldosterone cutoff ranges “indicating that the test was uninformative regardless of whether the results were positive or negative,” the researchers remark.
Subgroup analyses accounting for differences in treatment, clinical versus biochemical responses, the occurrence of hypokalemia, and the laboratory assay used did not alter the findings.
Leung et al conclude that “reliance on the SSST may misinform downstream treatment decisions and lead to missed opportunities for intervention, even in patients who would clearly respond to treatment.”
They say: “The results of our study suggest that removal of routine confirmatory testing from the diagnostic care pathway for PA may help to improve diagnostic accuracy and reduce the time needed for diagnosis and treatment for most patients.”
In an accompanying editorial, Jordana Cohen, from the University of Pennsylvania in Philadelphia, USA, says that “[t]his is the first study to rigorously assess the accuracy of the saline suppression test for confirming the diagnosis of PA.”
She comments: “The poor test performance adds to a litany of prior work questioning whether confirmatory testing has any value other than to hinder appropriate treatment.”
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Ann Intern Med 2025; doi:10.7326/ANNALS-24-03153
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