Cardiovascular Outcomes in Autonomous Cortisol Secretion and Nonfunctioning Adrenal Adenoma: A Systematic Review

There is growing evidence that autonomous cortisol secretion (ACS), previously known as subclinical Cushing syndrome, is associated with greater prevalence of cardiovascular (CV) risk factors. However, it is unclear whether ACS is associated with greater prevalence of CV outcomes compared with nonfunctioning adrenal adenomas (NFAAs). The objective of this study is to evaluate CV outcomes and CV risk factors in patients with adrenal adenoma with ACS compared with NFAA. A literature review was performed in Embase, Medline, Cochrane Library, and reference lists within selected articles. The study protocol was registered with PROSPERO. A literature search yielded six studies that met the inclusion criteria. Studies varied in their definitions of ACS and CV outcomes. Two retrospective longitudinal studies further demonstrated higher incidence of new CV events (ACS 16.7% vs NFAA 6.7%, P = 0.04) and higher CV mortality in patients with ACS (ACS 22.6% vs 2.5%, P = 0.02). The prevalence of CV outcomes in ACS was more than three times greater than in patients with NFAA. Three of five studies found that ACS was associated with higher prevalence of diabetes and hypertension. There was no difference in dyslipidemia or body mass index demonstrated in any study. There is heterogeneity among the few studies evaluating the association between ACS and CV outcomes. Although these studies suggest a higher risk of CV outcomes in patients with ACS, many did not adjust for known confounders. Larger, high quality, prospective studies are needed to evaluate this association and to identify modifiable risk factors.