OBJECTIVE: The natural course of adrenal incidentalomas, especially those with subclinical autonomous glucocorticoid production, i.e. subclinical Cushing's syndrome, and the risk that such conditions will evolve towards overt Cushing's syndrome are unknown. DESIGN: Longitudinal follow-up evaluation of a series of 284 consecutive patients with adrenal incidentaloma. METHODS AND RESULTS: Out of 284 consecutive patients with adrenal incidentaloma studied at our Institution in the last 15 years, 98 patients (23 with subclinical hypercortisolism) underwent surgery. Of 130 non-operated patients with a follow-up of at least 1 year, eight had subclinical hypercortisolism at diagnosis. We describe in detail four patients who developed overt Cushing's syndrome after 1-3 years of follow-up. Only one of these patients had subclinical hypercortisolism at first diagnosis. Estimated cumulative risk for a non-secreting adrenal incidentaloma to develop subclinical hyperfunction was 3.8% after 1 year and 6.6% after 5 years. For patients with masses with subclinical autonomous glucocorticoid overproduction, estimated cumulative risk to develop overt Cushing's syndrome was 12.5% after 1 year. CONCLUSIONS: In patients with adrenal incidentalomas the risk of progression towards overt Cushing's syndrome is not low, at variance with previous reports. A careful biochemical and hormonal follow-up is advisable in all patients who do not need surgery at first presentation.
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