Discordance and Shortcomings of Aldosterone Suppression Tests in Primary Aldosteronism

Abstract Background The saline suppression test (SST) and the captopril challenge test (CCT) have traditionally been used to confirm or exclude primary aldosteronism (PA). New guidelines recommend using these tests to predict the likelihood of unilateral PA. This study evaluated the diagnostic accuracy, consistency, and clinical implications of these tests. Methods We conducted a retrospective study of 531 patients with high-probability features of PA who underwent both SST and CCT to evaluate their accuracy and ability to predict unilateral PA. Adrenal lateralization and surgical treatment decisions were guided by individualized clinical judgment rather than strictly relying on SST/CCT results. Results The rate of PA diagnosis ranged from 47.8% to 97.2% based on SST and CCT criteria. Discordance rates between SST and CCT ranged from 10.9% to 51.6%. In analyses restricted to only patients with clinically overt PA, where suppression testing is not considered necessary, the positivity rates of the SST and CCT were still suboptimal and test discordance persisted. Among patients with lateralizing PA, 6.6% to 27.9% had either a negative SST or CCT interpretation, and among those who achieved Primary Aldosteronism Surgical Outcome-defined biochemical cure after unilateral adrenalectomy, 4.1% to 39.8% had either a negative SST or CCT, and up to 5.1% had false-negative results on both tests. Conclusions Well-established aldosterone suppression tests for PA demonstrated substantial inconsistency, false-negative interpretations, and the inability to reliably predict lateralization outcomes in PA. Aldosterone suppression testing, using SST and CCT, lack accuracy for the diagnosis and subtyping of PA in high-risk patients.