Progression of bilateral adrenal incidentalomas: a monocentric cohort study

Purpose: Bilateral adrenal incidentalomas (BAIs) are increasingly detected during abdominal imaging. Their initial clinical, hormonal, and radiological presentation is heterogeneous, and their natural history remains unclear. Current ESE/ENS@T guidelines lack specific recommendations for BAIs management.Methods: Retrospective single-center cohort study enrolling 185 consecutive non-operated patients referred between 2009 and 2023 to our endocrinology unit for BAIs (≥10 mm) with thorough assessment of hormonal, genetic and radiological data. Exclusion criteria were interfering comorbidities or incomplete data. Finally, 120 patients (63 females, mean age = 64.8 ± 8.2) were enrolled. Of these, 64 and 61 patients completed a minimum biochemical and radiological follow-up of 36 months, respectively.Results: At baseline, 56% of patients had mild autonomous cortisol secretion (MACS; 1-mg dexamethasone suppression test [1 mgDST] >1.8 µg/dl), and 44% had non-functioning (NF) BAIs. During follow-up, 32.1% of NF patients developed MACS (biochemical progression, BP), while 67.9% remained NF (biochemical stability, BS). Furthermore, 44.3% of patients showed radiological progression (RP) (increase in number and/or size of nodules ≥3 mm). The BP group had significantly higher baseline 1 mgDST values than the BS group (median: 1.3 vs. 1.1 µg/dl, p = 0.025). No other differences were detected between BP versus BS or RP versus radiological stability (RS) groups. In the RP group, only 7.4% of patients also showed BP. Patients with RP >10 mm (13.1%) had higher baseline 1 mgDST levels (3.5 vs. 2.2 µg/dl, p = 0.045).Conclusions: A non-negligible percentage of BAIs show hormonal and/or radiological progression. Our findings suggest that BAIs may represent a subgroup warranting individualized clinical reassessment and further prospective multicenter studies to define optimal surveillance strategies.