Long-term cardiac effects of adrenalectomy versus surveillance in mild cortisol excess: 5-year results from the prospective ITACA study

OBJECTIVE: To determine whether cardiac remodelling associated with mild autonomous cortisol secretion (MACS) is reversible after treatment and how trajectories compare with non-functioning adrenal incidentalomas (NFAI). DESIGN: Five-year prospective cohort study (ITACA; NCT04127552). METHODS: Sixty patients (35 MACS, 25 NFAI) underwent clinical, biochemical, and echocardiographic evaluations at baseline and after 1 and 5 years. MACS was managed with either active surveillance (AS, n = 22) or unilateral adrenalectomy (ADRX, n = 13). Longitudinal changes were analysed with linear mixed-effects models. RESULTS: At baseline, MACS had a higher prevalence of left-ventricular (LV) hypertrophy (46% vs 16%, P = .013) and diastolic dysfunction (34% vs 12%, P = .050), and greater LV mass index (LVMi) (median 100 vs 85 g/m², P = .011). Over time, the change in LVMi differed between NFAI, MACS-AS and MACS-ADRX (P = .004). At 1 year, LVMi fell by -14.8 g/m² (95%CI -28.7 to -0.9) after ADRX and rose by 13.7 g/m² (0.8 to 26.5) under AS. By 5 years, LVMi returned to baseline in both MACS subgroups, whereas NFAI increased by 22.4 g/m² (12.3 to 32.5; P < .001). Right-ventricular systolic excursion (TAPSE) improved only in AS (3.6 mm, 1.8 to 5.4; P = .001). Global LV systolic and diastolic indices deteriorated similarly across groups. Major adverse cardiac events occurred in 13.3% of MACS-AS, 12.5% of ADRX, and 5.6% of NFAI patients. CONCLUSIONS: MACS is associated with early concentric LV remodelling that regresses after adrenalectomy but rebounds within 5 years, leaving surgical and surveillance patients with comparable cardiac geometry. Under AS, remodelling stabilizes, whereas NFA continue a slow, progressive hypertrophic course. These findings support serial echocardiographic monitoring and underscore the need to test other cortisol-lowering therapies, alone or in combination with surgery, for durable cardioprotection.