“Nonfunctional” Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes: A Cohort Study

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Benign adrenal tumors are commonly discovered on abdominal imaging. Most are classified as nonfunctional and are considered to pose no health risk, but some are considered functional because they secrete hormones that increase risk for metabolic and cardiovascular diseases.


To evaluate the hypothesis that nonfunctional adrenal tumors (NFATs) increase risk for cardiometabolic outcomes compared with absence of adrenal tumors.


Cohort study.


Integrated hospital system.


Participants with benign NFATs (“exposed”; n = 166) and those with no adrenal tumor (“unexposed”; n = 740), with at least 3 years of follow-up.


Medical records were reviewed from the time of abdominal imaging for development of incident outcomes (hypertension, composite diabetes [prediabetes or type 2 diabetes], hyperlipidemia, cardiovascular events, and chronic kidney disease) (mean, 7.7 years). Primary analyses evaluated independent associations between exposure status and incident outcomes by using adjusted generalized linear models. Secondary analyses evaluated relationships between NFATs and cortisol physiology.


Participants with NFATs had significantly higher risk for incident composite diabetes than those without adrenal tumors (30 of 110 [27.3%] vs. 72 of 615 [11.7%] participants; absolute risk, 15.6% [95% CI, 6.9% to 24.3%]; adjusted risk ratio, 1.87 [CI, 1.17 to 2.98]). No significant associations between NFATs and other outcomes were observed. Higher “normal” postdexamethasone cortisol levels (≤50 nmol/L) were associated with larger NFAT size and higher prevalence of type 2 diabetes.


Potential bias in the selection of participants and ascertainment of outcomes.


Participants with NFATs had a significantly higher risk for diabetes than those without adrenal tumors. These results should prompt a reassessment of whether the classification of benign adrenal tumors as “nonfunctional” adequately reflects the continuum of hormone secretion and metabolic risk they may harbor.

Primary Funding Source:

National Institutes of Health and Doris Duke Charitable Foundation.

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