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Ana Podbregar, Tomaž Kocjan, Matej Rakuša, Peter Popović, Manca Garbajs, Katja Goricar, Andrej Janez, and Mojca Jensterle

Most data on the natural history of nonfunctioning adrenal incidentalomas (NFAI) are provided by follow-ups up to 5 years. We conducted a 10.5 (9.1–11.9)-year prospective follow-up study of NFAI in 67 participants (20 (29.9%) males, 47 (70.1%) females) of mean age 57.9 (52.3–63.9) years and BMI 27.42 (24.07–30.56) kg/m2). We also evaluated the associations between baseline BMI and changes of NFAIs’ characteristics at follow-up. Progression to mild autonomous cortisol excess (MACE) was observed in 15 (22 %) patients, with 14 of them having post overnight dexamethasone suppression test (ODST) cortisol between 50 and138 nmol/L and only one > 138 nmol/L. The progression rate was significantly higher in overweight and obese than in normal-weight subjects. Patients that developed MACE had a significantly higher baseline mean cortisol after 1 mg ODST. Tumor enlargement ≥10 mm occurred in 8.9% of patients. In comparison with reports of shorter observational periods, we observed a higher growth rate ≥ 10 mm and higher progression rate from NFAI to MACE, particularly in overweight and obese subjects. All tumors had persistent radiological characteristics typical for adrenal adenoma. We concluded that the duration of the follow-up period is an important factor in characterizing the natural history of NFAI. Higher baseline BMI and higher baseline cortisol after ODST might predict the long-term likelihood of progression in hormonal activity. The magnitudes of observed progressions in growth or hormonal activity were clinically insignificant. Our long-term follow-up, therefore, clearly supports the general view that a long-term monitoring of patients with NFAI is not necessary.