Clinical and pharmacological determinants of serum dexamethasone concentrations during dexamethasone suppression test

Context: The 1-mg overnight dexamethasone suppression test (1-mg DST) is widely used to screen for hypercortisolism, but its interpretation may be affected by variability in dexamethasone exposure due to clinical and pharmacological factors. Objective: To evaluate determinants of serum dexamethasone levels during 1-mg DST and their impact on test interpretation. Methods: Observational study including 546 patients undergoing 1-mg DST with measurement of serum cortisol and dexamethasone levels. Clinical variables (age, BMI, eGFR) and concomitant medications were analyzed. Associations with dexamethasone levels were assessed using multivariable linear regression; suboptimal exposure (<4.5 nmol/L) was evaluated by logistic analysis. Results: Median dexamethasone concentration was 11.9 nmol/L. In multivariable analysis, age (β=0.24, p<0.001) and BMI (β=0.17, p=0.010) were independently associated with higher dexamethasone levels, whereas eGFR was not. Concomitant medications (PPIs, statins, calcium channel blockers) were associated with higher dexamethasone levels in univariable analyses, but not after sensitivity analyses. Age-stratified models showed that BMI and PPI use were associated with dexamethasone in patients <65 years, whereas statins and PPIs were determinants in those ≥65 years. BMI and eGFR remained significant after excluding patients with mild autonomous cortisol secretion. Suboptimal dexamethasone exposure occurred in 3.3% of patients and was frequently associated with inadequate cortisol suppression. Conclusions: Age and BMI emerged as determinants of dexamethasone exposure during 1-mg DST, while the impact of renal function and medications appears limited after adjustment. Measuring dexamethasone may improve test interpretation; however, once adequate dexamethasone exposure is achieved, higher dexamethasone levels are not associated with additional cortisol suppression.