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.