Confirmatory Testing for Primary Aldosteronism : A Study of Diagnostic Test Accuracy.

Background: Confirmatory testing to verify the diagnosis of primary aldosteronism (PA) in patients who have an abnormal screening result is of uncertain benefit.

Objective: To perform a blinded assessment of the seated saline suppression test (SSST).

Design: Diagnostic test accuracy study. (ClinicalTrials.gov: NCT04422756).

Setting: The regional Endocrine Hypertension Clinic in Calgary, Alberta, Canada.

Participants: 156 adults with a positive screening result for PA.

Intervention: The SSST was done by administering 2 L of 0.9% sodium chloride intravenously over 4 hours with the patient seated.

Measurements: Treatment response was considered the reference standard for determining disease status and was based on blood pressure lowering, reduction of antihypertensive drug dose, and normalization of biochemistry. Measures of diagnostic test accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value, were estimated.

Results: Post-SSST aldosterone concentrations measured using immunoassay overlapped between treatment responders (median, 329 pmol/L [IQR, 227 to 525 pmol/L]) and nonresponders (median, 255 pmol/L [IQR, 162 to 346 pmol/L]). The SSST could not discriminate between response statuses (area under the curve, 62.1% [95% CI, 45.1% to 79.1%]). The positive and negative likelihood ratios were equivocal for aldosterone cutoffs ranging from 140 to 300 pmol/L. These findings remained consistent after differences in treatment, occurrence of hypokalemia, and laboratory assay used were accounted for.

Limitation: The study population had many patients with high-risk features of PA and few nonresponders.

Conclusion: The SSST is associated with a high false-negative rate, and reliance on it may lead to missed opportunities for intervention.

Primary funding source: The Canadian Institutes of Health Research, Hypertension Canada, and the Heart and Stroke Foundation of Canada.