Long-Term Cardiac Effects of Adrenalectomy Versus Surveillance in Mild Cortisol Excess: 5-Year Results from the prospective ITACA Study.
De Alcubierre D., Ferrari D., Tomaselli A., Moscucci F., Bonaventura I., Francia A., Vozza E., Lospinuso I., Ettorre E., Hasenmajer V., Minnetti M., Sbardella E., Tenuta M., Morelli S., Paganini AM., Isidori AM., Pofi R.
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=0.013) and diastolic dysfunction (34% vs 12%, p=0.050), and greater LV mass index (LVMi) (median 100 vs 85 g/m², p=0.011). Over time, the change in LVMi differed between NFAI, MACS-AS and MACS-ADRX (p=0.004). 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 < 0.001). Right-ventricular systolic excursion (TAPSE) improved only in AS (3.6 mm, 1.8 to 5.4; p = 0.001). 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 five years, leaving surgical and surveillance patients with comparable cardiac geometry. Under AS, remodelling stabilises, 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.