Subtype- and treatment-based analysis of calcium dynamics in primary aldosteronism

Abstract Objective Primary aldosteronism (PA) adversely affects cardiovascular and renal health and has been linked to increased urinary calcium excretion, elevated parathyroid hormone (PTH) levels, and reduced bone mineral density. Although adrenalectomy and mineralocorticoid receptor antagonists (MRAs) are established treatments, their differential effects on calcium dynamics across PA subtypes remain unclear. Design We conducted a retrospective observational study, analyzing a large, well-characterized cohort on calcium metabolism in PA. A total of 352 patients with PA and 57 controls were evaluated. Methods Clinical and biochemical parameters, including intact PTH (iPTH) and urinary electrolyte levels, were retrospectively assessed. Comparative analyses were performed before and after treatment in 43 patients with unilateral PA (UPA) and 131 patients with bilateral PA (BPA), with a direct comparison of adrenalectomy and MRAs in UPA. Results Patients with PA had higher urinary fractional excretion of calcium (FECa) (1.28% vs. 1.04%, p 0.001) and iPTH (60.0 vs. 57.0 pg/mL, p = 0.047) than controls, with more pronounced abnormalities in UPA (FECa, 1.50%, iPTH 73.1 pg/mL). Both treatments reduced FECa and iPTH levels, but adrenalectomy resulted in greater improvement than MRAs in the UPA (FECa, 0.68% post-MRA vs. 0.36% post-adrenalectomy). In the BPA group, MRAs decreased FECa, irrespective of disease severity. Conclusion Adrenalectomy was associated with greater improvements in calcium abnormalities than MRAs in patients with UPA, consistent with its cardiovascular benefits. These findings underscore the importance of subtype-specific strategies and suggest that adrenalectomy may offer additional benefits beyond cardiovascular outcomes.