A new LC-MS/MS assay for serum cortisol, cortisone, and dexamethasone: real-world utility for the interpretation of the 1-mg overnight dexamethasone suppression test
Authors' conclusion
Very low post-DST DEX concentrations are rare, and DST interpretation often remains informative even when DEX is below conventional thresholds, supporting a selective rather than routine use of DEX measurement. LC-MS/MS cortisol provides excellent discrimination with thresholds close to CLIA practice; cortisone appears best suited as an adjunct marker.
Study context
- Population
- Patients undergoing 1-mg overnight dexamethasone suppression test (DST): 351 controls, 135 non-functioning adrenal incidentaloma, 14 aldosterone-cortisol cosecretion, 116 mild autonomous cortisol secretion, 20 overt Cushing's syndrome; clinically adjudicated diagnoses
- Participants
- 636 patients
- Comparison
- Cortisol by chemiluminescent immunoassay (CLIA) vs LC-MS/MS after 1-mg DST
- Outcome
- AUC for predicting overt hypercortisolism
Methodological detailsconsecutive, real-world observational
- Consecutive
- Real-world observational
Performance
As reported in the abstract
| Test or model | AUC |
|---|---|
| CLIA cortisol | 0.976 |
| LC-MS/MS cortisol | 0.974 |
| LC-MS/MS cortisone | 0.959 |
AUC
CLIA cortisol0.976
LC-MS/MS cortisol0.974
LC-MS/MS cortisone0.959
Further findings
| Outcome | CLIA cortisol | LC-MS/MS cortisol | LC-MS/MS cortisone | P value |
|---|---|---|---|---|
| AUC for diagnosis of all forms of hypercortisolism | ||||
| AUC | 0.961 | 0.951 | 0.931 | |
| Post-DST DEX by BMIObesity vs BMI <30 kg/m² | P = 0.030 |
- Post-DST dexamethasone (DEX) by BMI: Obesity 4.87 ± 2.26 ng/mL
- Post-DST DEX by BMI: BMI <30 kg/m² 4.40 ± 2.44 ng/mL
Low DEX values and DST interpretability
- Lower-tail DEX values were uncommon; even below lower-tail thresholds, DST results often remained clinically interpretable
- LC-MS/MS cortisol optimal cut-offs were close to CLIA practice
Original publication
A new LC-MS/MS assay for serum cortisol, cortisone, and dexamethasone: real-world utility for the interpretation of the 1-mg overnight dexamethasone suppression test. Eur J Endocrinol. Published 25 July 2026. doi:10.
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