Simultaneous Liquid Chromatography-Tandem Mass Spectrometry Quantification of Cortisol and Dexamethasone Establishes a Platform-Specific Dexamethasone Lower Limit and Improves Diagnostic Specificity of the 1-mg Overnight Dexamethasone Suppression Test
Authors' conclusion
Concurrent LC-MS/MS measurement of Dex and cortisol enables assay-specific and population-specific Dex LLNs that, when applied, reduce false-positive DST interpretations with minimal impact on sensitivity. Reporting Dex alongside cortisol and flagging samples below LLN may improve clinical DST interpretation.
Study context
- Population
- Post-DST serum samples with measurable cortisol and dexamethasone (Dex) via LC-MS/MS, 1-mg overnight dexamethasone suppression test (DST) for Cushing's syndrome (CS) screening
- Participants
- 221 post-DST serum samples
- Comparison
- Post-DST cortisol interpretation before vs after excluding samples with Dex < LLN (LC-MS/MS)
- CSn = 80
- Adrenal incidentalomasn = 93
- Controlsn = 48reference
- Outcome
- Diagnostic performance of post-DST cortisol before and after excluding samples with Dex < LLN2.5% (primary threshold)
Performance
As reported in the abstract
Post-DST cortisol for identifying CS
AUC of post-DST cortisol for CS, all samples
0.96
95% CI 0.93–0.98
Further findings
Dex LLN values (non-CS, post-DST cortisol ≤ 1.8 μg/dL, n = 88)
ng/mL
- LLN2.5%
- 1.706
- LLN5%
- 1.889
- LLN10%
- 2.399
Dex levels across samples
- Dex range: below detection to
- 32.85 ng/mL
- Median Dex
- 3.61 ng/mL
- Undetectable Dex
- 4 samples (1.7%)
- Excluded with Dex < LLN2.5%
- 21 samples (9.50%)
- Samples remaining
- 200
Sensitivity analyses at LLN5% and LLN10%
- Results consistent across other LLN thresholds
Original publication
Simultaneous Liquid Chromatography-Tandem Mass Spectrometry Quantification of Cortisol and Dexamethasone Establishes a Platform-Specific Dexamethasone Lower Limit and Improves Diagnostic Specificity of the 1-mg Overnight Dexamethasone Suppression Test. Endocr Pract. Published 30 December 2025. doi:10.
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