Adrenal disease

Overnight Dexamethasone Suppression Test: Enhanced Accuracy With Late-afternoon Cortisol and Morning/Late-afternoon ACTH

J Clin Endocrinol MetabPublished Diagnostic accuracy study

Authors' conclusion

Late-afternoon cortisol measurement is a novel modification that enhances ODST specificity. ACTH measurement was particularly useful in COCP and CKD. Before widespread integration in clinical practice, further validation is required.

Study context

Population
Healthy adults, combined oral contraceptive pill (COCP) users, chronic kidney disease (CKD), treatment-naïve A-CS, posttreatment CD in remission or persistence; standard 1-mg dexamethasone suppression test with cortisol/ACTH at 8–9 AM and 3–4 PM
Participants
60 / 29 / 29 / 33 / 23 / 31
Comparison
Overnight dexamethasone suppression (ODS) 4 PM cortisol and 8 AM/4 PM ACTH vs standard ODS 8 AM cortisol
  • Healthy adultsn = 60
  • COCPn = 29
  • CKDn = 29
  • A-CSn = 33
  • Cushing disease in remission (CD-R)n = 23
  • CD-Pn = 31
Outcome
Specificity of ODS cortisol (cutoff 1.8 μg/dL) and ACTH (cutoff 10 pg/mL), 8 AM and 4 PM
Methodological detailsprospective, single-centre
  • Prospective
  • Single-centre

Performance

As reported in the abstract

Test or modelSensitivity 8 AM and 4 PM ACTHSpecificity 8 AM cortisolSpecificity 4 PM cortisolSpecificity 8 AM ACTHSpecificity 4 PM ACTH
Healthy adults— not stated in the abstract95%100%95%100%
COCP— not stated in the abstract55%79%100%100%
CKD— not stated in the abstract17%52%96.6%100%
A-CS100%— not stated in the abstract— not stated in the abstract— not stated in the abstract— not stated in the abstract

Sensitivity 8 AM and 4 PM ACTH

Healthy adults— not stated in the abstract
COCP— not stated in the abstract
CKD— not stated in the abstract
A-CS100%

Specificity 8 AM cortisol

Healthy adults95%
COCP55%
CKD17%
A-CS— not stated in the abstract

Specificity 4 PM cortisol

Healthy adults100%
COCP79%
CKD52%
A-CS— not stated in the abstract

Specificity 8 AM ACTH

Healthy adults95%
COCP100%
CKD96.6%
A-CS— not stated in the abstract

Specificity 4 PM ACTH

Healthy adults100%
COCP100%
CKD100%
A-CS— not stated in the abstract

— not stated in the abstract

Further findings

OutcomeP value
ODS 4 PM vs 8 AM cortisolHealthy adults: 4 PM vs 8 AM · lower at 4 PMP = 0.003
ODS 4 PM vs 8 AM cortisolCOCP: 4 PM vs 8 AM · lower at 4 PMP < 0.001
ODS 4 PM vs 8 AM cortisolCKD: 4 PM vs 8 AM · lower at 4 PMP < 0.001
ODS 4 PM vs 8 AM cortisolCD-R: 4 PM vs 8 AM · lower at 4 PMP = 0.001

Diagnostic accuracy for differentiating CD-R from CD-P

ODS 4 PM cortisol
98.1%
ODS 8 AM ACTH
81.5%
ODS 4 PM ACTH
81.5%

ODS 4 PM vs 8 AM cortisol

Difference not significant in treatment-naïve A-CS and CD-P

Original publication

Overnight Dexamethasone Suppression Test: Enhanced Accuracy With Late-afternoon Cortisol and Morning/Late-afternoon ACTH. J Clin Endocrinol Metab. Published 16 September 2025. doi:10.1210/clinem/dgaf513

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