Association of Post-Dexamethasone Cortisol With Cardiovascular and Metabolic Comorbidities in Patients With...

To determine whether post-dexamethasone suppression test (DST) cortisol within the conventionally suppressed range is associated with documented atherosclerotic cardiovascular disease (ASCVD) and cardiometabolic comorbidities in nonfunctioning adrenal adenomas (NFAAs).

This retrospective single-center study included 444 adults with homogeneous adrenal lesions smaller than 4 cm, unenhanced computed tomography attenuation of 10 Hounsfield units or less, no adrenal hormone excess, and post-1 mg DST cortisol of 1.8 μg/dL or less. Documented ASCVD was the primary outcome; metabolic syndrome and other cardiometabolic conditions were secondary outcomes. ROC analysis and multivariable logistic regression were performed, with cortisol modeled per 0.1 μg/dL increase.

Women comprised 69.6% of the cohort; median age was 57 years and median post-DST cortisol was 0.96 μg/dL. Each 0.1 μg/dL increase was independently associated with 21% higher odds of documented ASCVD (adjusted odds ratio, 1.21; 95% CI, 1.09-1.34; P<.001). The ROC area under the curve was 0.820 (95% CI, 0.781-0.860). The exploratory Youden-optimal value was 0.985 μg/dL, with 87% sensitivity, 71% specificity, 59% positive predictive value, and 92% negative predictive value. Post-DST cortisol was also independently associated with metabolic syndrome (adjusted odds ratio, 1.24; 95% CI, 1.13-1.35; P<.001).

Higher post-DST cortisol within the suppressed range was independently associated with documented ASCVD and showed substantial discrimination. These findings support a cardiometabolic gradient below the mild autonomous cortisol secretion threshold but do not establish a diagnostic cutoff.