Time-Dependent Increase in Cortisol After 1 mg Overnight Dexamethasone Suppression Test in Adrenal Incidentalomas

Background Guidelines recommend the 1 mg overnight dexamethasone suppression test (1 mg-ODST) for diagnosing mild autonomous cortisol secretion (MACS) in adrenal incidentalomas (AI). Age may influence cortisol levels after 1 mg-ODST (post-ODST cortisol levels). This study investigated changes in post-ODST cortisol levels over time in Korean patients with AI. Methods This retrospective, multi-center cohort study included 1,063 patients with AI from four tertiary hospitals between 2003 and 2022. Post-ODST cortisol changes were evaluated using the ODST ratio (last to baseline measurement). A generalized additive model assessed the association between age and post-ODST cortisol levels. Multivariable logistic regression estimated odds ratios (OR) for post-ODST cortisol progression by follow-up duration. Results The ODST ratio increased with follow-up duration (β = 0.063, P <0.001). Least-square mean ± standard error of the ODST ratio was higher in the 2–5-year (1.20 ± 0.02, P <0.001) and >5-year groups (1.66 ± 0.06, P <0.001) than in the <2-year group (1.12 ± 0.03). Age showed a significant non-linear effect on post-ODST cortisol levels (P <0.001). The risk of post-ODST cortisol progression was higher in the >5-year group than in the <2-year group for nonfunctioning AI (OR = 5.44, 95% confidence interval [CI] = 2.90–10.23, P <0.001) and MACS (OR = 3.86, 95% CI = 1.19–12.46, P = 0.024). Conclusion Cortisol levels after 1 mg-ODST increased over time, suggesting an age-related effect and highlighting the need for age-tailored diagnostic and management strategies for MACS in older patients with AI.