Context  Adrenal incidentalomas (AI) have often been associated with a high prevalence of insulin resistance (IR) and cardiovascular risk factors, although direct measurement of insulin sensitivity (IS) has never been carried out.

Objective  We aimed to investigate whether the morphological and hormonal features of AI correlate with the presence and severity of IR, using the hyperinsulinaemic euglycaemic clamp (HEC).

Design and Measurements  Forty patients with AI (22 women) with a mean age of 58·5 ± 11·1 years underwent hormonal and morphological evaluation. Nineteen patients with AI without known history of diabetes mellitus (DM) or impaired glucose tolerance (IGT) and 17 matched controls underwent oral glucose tolerance test (OGTT) and hyperinsulinaemic euglycaemic clamp (HEC).

Results  Diabetes mellitus was observed in 13 patients (33%), while three (8%) had IGT. Thirty-one of the AI were nonfunctioning (82·5%), whereas two (5%) secreted cortisol (Cushing’s syndrome) and seven (12·5%) showed subclinical secretion of cortisol. The 19 patients with nonfunctioning AI were more insulin resistant than controls (glucose up-take: 4·58 ± 1·80 vs 5·85 ± 2·48 mg/kg/min respectively; P = 0·01); IS was inversely related to the mass size (r = −0·57; P = 0·04), free urinary cortisol (r = −0·68; P = 0·01), serum cortisol after 1-mg dexamethasone suppression (−0·65; P = 0·02) and percentage of trunk fat mass (−0·77; P = 0·02) and directly related to serum adreno cortico tropic hormone (ACTH) (r = 0·62; P = 0·03). After performing multivariate regression, the mass size was found to be the most powerful predictor of IR.

Conclusion  Our study showed a high prevalence of insulin resistance in patients with nonfunctioning AI and suggests its possible involvement in AI growth.