Patients With Apparently Nonfunctioning Adrenal Incidentalomas May Be at Increased Cardiovascular Risk Due to Excessive Cortisol Secretion

Context: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. Objective: Our objective was to investigate CVR in patients with NFAI. Design and Setting: This case-control study was performed in a tertiary general hospital. Subjects: Subjects included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. Main Outcome Measures: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. Results: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. Conclusions: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.