Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2025
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.
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Gao Yumeng, Mu Danni, Ma Yichen, Li Yuemeng, Li Ming, Hu Yingying, Qiu Ling, Yu Songlin, Cheng Xinqi
Аннотация
OBJECTIVE: The 1-mg overnight dexamethasone suppression test (DST) is a common screen for Cushing's syndrome (CS) but yields false-positives when post-DST dexamethasone (Dex) exposure is inadequate. We investigated whether simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement of cortisol and Dex, combined with assay-specific Dex lower limits of normal (LLNs), improves DST interpretation.
METHODS: In this prospective study, 221 post-DST serum samples (80 with CS, 93 with adrenal incidentalomas, and 48 controls) had measurable cortisol and Dex levels via LC-MS/MS. In non-CS individuals with post-DST cortisol ≤ 1.8 μg/dL (n = 88), we determined LLN values: LLN2.5% = 1.706 ng/mL, LLN5% = 1.889 ng/mL, and LLN10% = 2.399 ng/mL. We compared diagnostic performance before and after excluding samples with Dex < LLN, using LLN2.5% as the primary threshold, with sensitivity analyses at LLN5% and LLN10%.
RESULTS: Among the 221 samples, Dex levels ranged from below detection to 32.85 ng/mL (median: 3.61 ng/mL); 4 samples (1.7%) had undetectable Dex. Excluding 21 samples (9.50%) with Dex < LLN2.5%, 200 samples left. Post-DST cortisol effectively identified CS (area under the receiver operating characteristic curve: 0.96, 95% confidence interval: 0.93-0.98); after removing low-Dex samples, the area under the receiver operating characteristic curve remained consistently high. Results were consistent across other LLN thresholds.
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.
METHODS: In this prospective study, 221 post-DST serum samples (80 with CS, 93 with adrenal incidentalomas, and 48 controls) had measurable cortisol and Dex levels via LC-MS/MS. In non-CS individuals with post-DST cortisol ≤ 1.8 μg/dL (n = 88), we determined LLN values: LLN2.5% = 1.706 ng/mL, LLN5% = 1.889 ng/mL, and LLN10% = 2.399 ng/mL. We compared diagnostic performance before and after excluding samples with Dex < LLN, using LLN2.5% as the primary threshold, with sensitivity analyses at LLN5% and LLN10%.
RESULTS: Among the 221 samples, Dex levels ranged from below detection to 32.85 ng/mL (median: 3.61 ng/mL); 4 samples (1.7%) had undetectable Dex. Excluding 21 samples (9.50%) with Dex < LLN2.5%, 200 samples left. Post-DST cortisol effectively identified CS (area under the receiver operating characteristic curve: 0.96, 95% confidence interval: 0.93-0.98); after removing low-Dex samples, the area under the receiver operating characteristic curve remained consistently high. Results were consistent across other LLN thresholds.
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.