Adrenal incidentalomas: a manifestation of the metabolic syndrome?

Recent evidence suggests that insulin is mitogenic on the adrenal cortex and stimulates adrenocortical tumor formation. We, investigated whether hyperinsulinemia is present in 13 patients with incidentally detected adrenal tumors. Patients with adrenal incidentalomas were obese (mean BMI 29.7 +/- 1.2 kg/m2, normal < 25; % body fat 35 +/- 1.5%, normal < 30%) with increased abdominal fat deposition (waist to hip ratio 0.92 +/- 0.02, normal < 0.85). All 13 patients were insulin resistant. Five had NIDDM, of the remaining patients 5 had fasting insulin concentrations above 15 microE/ml, and all 8 patients had elevated insulin concentrations after 75 g of glucose orally. To further investigate the potential role of insulin we examined its effects on the NCI-h295 cell line. Insulin (1-100 micrograms/ml) stimulated cell proliferation in a time and dose-dependent matter without affecting cortisol synthesis. At this concentrations insulin was equally potent to IGF I (10-80 ng/ml) or IGF II (10-100 ng/ml). We conclude that the majority of patients with adrenal incidentalomas are insulin-resistant/hyperinsulinemic. Insulin stimulates adrenal cancer cell lines in vitro. We propose that adrenal incidentalomas are a newly recognized manifestation of the metabolic syndrome comparable to insulin-mediated stimulation of the ovary in the polycystic ovary syndrome.