FRI142 The Pathophysiologic Spectrum Of Primary Aldosteronism Determined Via Saline Suppression Testing In Overweight Hypertensive And Pre-hypertensive People

Abstract

Abstract Disclosure: W.W. Parksook: None. J.M. Brown: Consulting Fee; Self; Bayer, Inc. J. Milks: None. A. Moore: None. Y. Niebuhr: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; Corcept, HRA Pharmaceuticals, Mineralys. Background: Emerging evidence shows that primary aldosteronism is not a categorical condition, but rather a pathophysiologic continuum that manifests across a broad range of severity. Saline suppression testing has long been used to “confirm” primary aldosteronism while employing relatively arbitrary and categorical thresholds. Methods: Overweight to obese participants with metabolic risk factors and pre-hypertension or stage 1 hypertension with suppressed renin activity (<1.0 ng/mL/h) (n=42) underwent deep phenotyping protocols to assess the pathophysiologic continuum of the primary aldosteronism phenotype. Participants completed a seated saline suppression test (SSST), to maximally suppress Angiotensin II-mediated aldosterone production, and dexamethasone suppression and cosyntropin stimulation testing, to maximally suppress and stimulate ACTH-mediated aldosterone production. The association of each parameter with the continuum of aldosterone levels was assessed using linear regression. Results: Following SSST, there was a continuum of non-suppressible and renin-independent aldosterone production. Categorically, 29% of participants had post-SSST plasma aldosterone levels ≥10 ng/dL, and another 45% had levels 6-10 ng/dL; however, there was a continuous spectrum of aldosterone values above and below these arbitrary thresholds. Across the continuum of post-SSST aldosterone levels, greater non-suppressibility of aldosterone was associated with greater non-suppressibility of aldosterone post-dexamethasone (β= 1.05, P<0.001), greater stimulation of aldosterone post-cosyntropin administration (β= 1.42, P<0.001), and greater aldosterone-to-renin ratio (β= 3.44, P=0.01). Conclusion: Despite existing categorical thresholds for SSST, dynamic phenotyping studies in overweight/obese stage I hypertensive and pre-hypertensive individuals demonstrate a continuum of non-suppressible and renin-independent aldosterone production following SSST that parallels higher levels of ACTH-dependent aldosterone production. These findings underscore the fallibility of currently recommended diagnostic limits for SSST and suggest that primary aldosteronism pathophysiology transcends these relatively arbitrary thresholds. Presentation: Friday, June 16, 2023