Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion.
BACKGROUND
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.


METHODS
This case-control study was performed in a tertiary general hospital.


METHODS
SUBJECTS included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging.


METHODS
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.
Department of Endocrinology and Diabetes (I.I.A., A.C.M., A.K.G., G.P.P.), General Hospital of Athens "G. Gennimatas," and Endocrine Unit (G.A.K., D.A.T., K.I.A.), Department of Pathophysiology, National University of Athens, 11527 Athens, Greece; Endocrine Unit (I.I.A., D.J.H.), Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School, Attikon University Hospital, 12462 Athens, Greece; and Vascular Laboratory (G.E.K., C.M.P.), Department of Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, 11528 Athens, Greece.
Ioannis I
II
Androulakis
Gregory A
GA
Kaltsas
Georgios E
GE
Kollias
Athina C
AC
Markou
Aggeliki K
AK
Gouli
Dimitrios A
DA
Thomas
Krystallenia I
KI
Alexandraki
Christos M
CM
Papamichael
Dimitrios J
DJ
Hadjidakis
George P
GP
Piaditis
D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D005260:Female; D005951:Glucose Tolerance Test; D006439:Hemodynamics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D006854:Hydrocortisone