Cardiovascular outcomes in autonomous cortisol secretion and nonfunctioning adrenal adenoma: a systematic review
Open accessAbstract
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.
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A study with up to 15 years of follow-up in patients with autonomous cortisol secretion documented increased cardiovascular morbidity (43% vs 8.8%, P < .005) and mortality (22.6% vs 2.5%, P < .02) compared with nonfunctioning adrenal incidentaloma.
“A study with up to 15 years of follow-up in patients with ACS has documented increased cardiovascular morbidity (43% vs 8.8%, P < .005) and mortality (22.6% vs 2.5%, P < .02) in ACS patients compared with nonfunctioning AI.”
From Adrenal incidentaloma (2020) · cites this paper as [247]
A recent systematic review showed that patients with autonomous cortisol secretion had a higher prevalence of cardiovascular events (16.7-26.8%) compared with patients with nonfunctional adrenal incidentaloma (6.7-10.4%).
“A recent systematic review showed that ACS patients had a higher prevalence of cardiovascular events (16.7-26.8%) compared with patients with nonfunctional AI (6.7-10.4%) (79,244,245,247).”
From Adrenal incidentaloma (2020) · cites this paper as [247]
Adrenalectomy improves cardiovascular outcome and mortality in ACS patients.
“A recent systematic review addressed cardiovascular benefit in ACS patients (247) with adrenalectomy improving cardiovascular outcome and mortality (4,247).”
From Adrenal incidentaloma (2020) · cites this paper as [247]
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Chu, W.-K., He, J., Peng, Y.-B., Fu, H.-W., Wu, V., & Yuan, H. (2025) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/14703203251347397
Akkuş, G., Kolsuz, İ., Arslan, Y. K., Pişkin, F. C., Evran, M., Sert, M., Tetıker, T., İnce, Y. E., Örs, A., Yılmaz, N., et al. (2026) · Endocrine · doi:10.1007/s12020-026-04667-8
MACS: mild by definition, challenging by nature
Bluszcz, G., Roszkowska, Z., Domański, J., Sharabi, A., Rapiejko, J., Malek, J., Ambroziak, U., & Bobrowicz, M. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1957127
- Authors
- Park, J., De Luca, A., Dutton, H., Malcolm, J. C., & Doyle, M.-A.
- Affiliations
- Western University (CA)
- University of Ottawa, Ottawa, Ontario, Canada
- University of Ottawa (CA)
- Corresponding author
- Doyle, Mary-Anne
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2019-03-25
- Volume
- 3
- Issue
- 5
- Pages
- 996-1008
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC6497919
- OpenAlex
- W2943502295
- Cited by
- 46
- References
- 42
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 6
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- autonomous cortisol secretion, subclinical Cushing's syndrome, non-functioning adrenal adenoma, cardiovascular outcomes, cardiovascular risk factors, cardiovascular mortality, cardiovascular events, diabetes mellitus, hypertension, dyslipidemia, body mass index
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