Adrenal incidentalomas are frequently evaluated with the overnight dexamethasone suppression test (DST) to screen for cortisol autonomy. A post-DST cortisol cutoff of ≤1.8 µg/dL is commonly used to define nonfunctioning adrenal tumors and to exclude mild autonomous cortisol secretion (MACS). However, evidence suggests cardiometabolic risk may vary across values below this threshold. This retrospective cross-sectional study aimed to compare cardiometabolic risk across three post-DST cortisol strata in patients with adrenal incidentaloma using standard metabolic parameters and atherogenic indices.
The study retrospectively reviewed 156 patients with adrenal incidentaloma. Participants were grouped by their post-DST cortisol level into: Group 1 (≤0.9 µg/dL, n = 48), Group 2 (0.91–1.79 µg/dL, n = 60), and Group 3 (≥1.8 µg/dL, n = 48). Demographic data, blood pressure measurements, and laboratory values reflective of glucose metabolism and lipid status were collected and compared across groups. The investigators used groupwise comparisons and Spearman correlation analyses to examine relationships between post-DST cortisol and cardiometabolic parameters.
Compared variables included systolic and diastolic blood pressure, prevalence of hypertension and diabetes mellitus, fasting glucose, HbA1c, total cholesterol, LDL cholesterol (LDL-C), non-HDL cholesterol, and additional indices of cardiometabolic risk. Atherogenic indices comprised the triglyceride–glucose (TyG) index, plasma atherogenic index (PAI), and Castelli Risk Indices I and II. These indices were assessed alongside conventional lipid and glycemic measures to characterize cardiometabolic phenotype across cortisol categories.
Blood pressure values and the prevalence of hypertension increased significantly across the three post-DST cortisol categories. Notably, Group 2 (0.91–1.79 µg/dL) had significantly higher systolic and diastolic blood pressure and a greater prevalence of hypertension compared with Group 1 (≤0.9 µg/dL). Diabetes mellitus prevalence was also greater in Group 2 than in Group 1.
Glycemic measures differed across groups: fasting glucose and HbA1c varied among the three categories, with HbA1c significantly higher in Group 2 than Group 1. Lipid parameters demonstrated graded differences as well. Total cholesterol, LDL-C, and non-HDL cholesterol were significantly different across cortisol strata; LDL-C was higher in Group 2 compared with Group 1.
The TyG index and Castelli Risk Indices I and II showed statistically significant differences across cortisol categories. Pairwise comparisons indicated that most of the differences in these indices occurred between Groups 1 and 3, although the intermediate group (Group 2) occupied a middle position in the distribution. The plasma atherogenic index (PAI) was evaluated alongside these indices but the abstract highlights the TyG and Castelli indices as differing across categories.
Spearman correlation analyses demonstrated positive correlations between post-DST cortisol levels and multiple cardiometabolic measures. Higher post-DST cortisol was associated with higher blood pressure, worse markers of glucose metabolism (including fasting glucose and HbA1c), more atherogenic lipid profiles, and elevated values of several atherogenic indices. These correlations support a graded relationship rather than a binary distinction between suppressed and non-suppressed cortisol results.
Patients with post-DST cortisol levels in the 0.91–1.79 µg/dL range exhibited an intermediate cardiometabolic phenotype. Compared with patients with more complete suppression (≤0.9 µg/dL), Group 2 already showed significant abnormalities in blood pressure, HbA1c, and LDL-C, as well as higher prevalence of hypertension and diabetes. Although some atherogenic indices showed the strongest differences between the lowest and highest cortisol groups, Group 2 consistently fell between Groups 1 and 3 across multiple measures.
These findings indicate that individuals with post-DST cortisol below the conventional MACS cutoff are not necessarily a metabolically homogeneous or uniformly benign group. An intermediate increase in cardiometabolic risk markers in the 0.91–1.79 µg/dL range suggests the need for careful cardiometabolic assessment and monitoring in patients with adrenal incidentaloma even when DST results are below the traditional MACS threshold. The authors advocate for prospective research to define risk across the continuum of post-DST cortisol values and to determine whether management thresholds or surveillance strategies should be revised.
The study was retrospective and cross-sectional, limiting causal inference and temporal assessment of cardiovascular outcomes. The investigation was approved by the Eskişehir Osmangazi University Non-Interventional Clinical Research Ethics Committee (Approval No. 14, dated November 28, 2023). The authors declared no competing interests. Specific details beyond those reported in the abstract (for example sample selection specifics, statistical methods, or full numeric results) were not provided in the source abstract and therefore are not reported here.