Primary aldosteronism beyond laterality: integrating subtype assignment with outcome-oriented risk stratification

Primary aldosteronism (PA) has traditionally been approached as a disorder of anatomical subtype classification, with treatment decisions largely structured around distinction between unilateral and bilateral disease. Although this framework remains essential for therapeutic orientation, it does not fully account for the marked heterogeneity in cardiovascular, renal, and metabolic outcomes observed across patients with PA. Increasing evidence suggests that long-term prognosis in PA reflects not only laterality, but also the cumulative burden of mineralocorticoid receptor activation, current hormonal activity, and interindividual tissue susceptibility. Clinical target-organ damage, persistent renin suppression, magnitude of aldosterone excess, steroidogenic profiles, cortisol co-secretion, and somatic or germline molecular features may each provide complementary information that is not captured by subtype designation alone. In this review, we examine the limitations of a binary anatomical paradigm for risk estimation and summarise emerging evidence supporting a multidimensional framework integrating clinical burden, functional hormonal activity, and molecular context. We further discuss the implications of this framework for treatment adequacy assessment, longitudinal follow-up, and future endpoint-driven research. PA should therefore be considered not only a disorder requiring subtype assignment, but also a stratifiable cardiometabolic condition in which estimation of residual organ risk may be as clinically relevant as determination of anatomical laterality. Prospective validation is still required, but laterality alone appears insufficient for longitudinal risk stratification and treatment adequacy assessment in PA.