RC9.4 - ECE_1118 - Clinical and pharmacological determinants of serum dexamethasone concentrations during the dexamethasone suppression test

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Abstract Background The dexamethasone suppression test (DST) is recommended by the European Society of Endocrinology for the evaluation of endogenous hypercortisolism, including Cushing's syndrome (CS) and autonomous cortisol secretion (MACS) in adrenal incidentalomas. A 1 mg DST is considered normal when post-test serum cortisol is suppressed below 50 nmol/L (<1.8 μg/dL). Simultaneous measurement of serum dexamethasone allows for accurate identification of suboptimal drug exposure (<4.5 nmol/L), which may compromise test reliability. Interindividual variability in dexamethasone pharmacokinetics, influenced by patient clinical conditions and concomitant medications, represents a major challenge in clinical interpretation. Objective To investigate the clinical and pharmacological determinants of serum dexamethasone concentrations during the DST. Materials and Methods We conducted a retrospective observational study including 546 patients who underwent 1 mg DST overnight, with concurrent serum dexamethasone measurement. Serum dexamethasone concentrations were quantified using validated LC-MS/MS assays. The study population included 54 patients with CS (25 active CS and 29 with previously treated disease), 287 patients with adrenal incidentaloma (160 non-functioning adrenal incidentalomas and 127 MACS) and 205 suspected CS. Patients with known conditions potentially affecting dexamethasone metabolism, including hepatic insufficiency, were excluded. Data were analyzed to assess the relationships between serum dexamethasone levels and clinical and pharmacological variables. Results Patients aged ≥65 years exhibited higher dexamethasone concentrations compared with younger individuals (13.6 vs 10.4 nmol/L, P < .001), as did patients with BMI ≥ 25 kg/m2 (12.2 vs 9.6 nmol/L, P = .004). Dexamethasone concentrations were progressively higher with decreasing renal function, when patients were categorized into four estimated glomerular filtration rate (eGFR) classes (P < .01); on the contrary cortisol levels after 1 mg DST overnight were progressively lower with eGFR reduction. In age-stratified linear regression analyses (cut-off 65 years), serum dexamethasone levels showed a significant positive association with creatinine concentrations (P = .002). Concomitant use of proton pump inhibitors, statins or calcium channel blockers was independently associated with increased serum dexamethasone levels (all drugs P < .001). Suboptimal dexamethasone exposure (<4.5 nmol/L) was observed in 17 patients (3.1%), of whom 11 (64.7%) showed lack of cortisol suppression following DST. Conclusions Serum dexamethasone levels are significantly affected by patient clinical characteristics and concomitant medications. Recognition of these factors is crucial for optimizing the reliability of hypercortisolism screening, minimizing diagnostic errors and supporting personalized evaluation. Clinicians should consider age, BMI, renal function and potential drug interactions when interpreting DST results to ensure accurate diagnosis and avoid misclassification.

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