Development and validation of a sex- and age-adjusted dehydroepiandrosterone sulfate index for suspected adrenal insufficiency
Authors' conclusion
Age- and sex-adjusted DHEAS thresholds improve screening for adrenal insufficiency diagnosis, reducing unnecessary ACTH testing and enhancing clinical decision-making, particularly in patients with borderline baseline cortisol.
Study context
- Population
- Adults with suspected adrenal insufficiency (AI) undergoing ACTH stimulation testing (validation); training cohort of adult patients with dehydroepiandrosterone sulfate (DHEAS) and morning cortisol measurementsvalidation cohort
- Participants
- 71 adults
- Comparison
- Sex- and age-adjusted DHEAS-Index vs universal DHEAS threshold <0.2 µg/mL for AI
- Outcome
- Diagnostic performance of DHEAS-Index for classifying AI (cortisol 60' < 18 µg/dL)
Methodological details2-phase, retrospective training cohort, prospective external validation cohort
- 2-phase
- Retrospective training cohort
- Prospective external validation cohort
Performance
As reported in the abstract
Classifying AI (cortisol 60' < 18 µg/dL), validation cohort
| Strategy | Sensitivity | Specificity | NPV |
|---|---|---|---|
| DHEAS-Index | 93% | 79% | 98% |
| Universal DHEAS threshold | 80% | 89% | 94% |
Sensitivity
DHEAS-Index93%
Universal DHEAS threshold80%
Specificity
DHEAS-Index79%
Universal DHEAS threshold89%
NPV
DHEAS-Index98%
Universal DHEAS threshold94%
Further findings
| Outcome | Values | P value |
|---|---|---|
| Training cohort: DHEAS in morning cortisol <5 µg/dL vs >5 µg/dLDHEAS significantly lower | Cortisol <5 µg/dL 0.10 (range 0.10–0.22) µg/mL | P = 0.000 |
- Training cohort: DHEAS in morning cortisol <5 µg/dL vs >5 µg/dL: 3.307 measurements from 1.720 adult patients
Training cohort: DHEAS in morning cortisol <5 µg/dL vs >5 µg/dL
- Higher morning cortisol, male sex and younger age independently associated with higher DHEAS; older age predicted lower levels (all P = .000)
Discrimination of sex- and age-specific DHEAS cutoffs for AI (ROC)
- AUC across age and sex subgroups
- 75.2% to 90.5%
- Highest AUC, men aged 18-29
- 90.5%
Correlation of DHEAS-Index with delta cortisol increase during ACTH test
- Rho
- 0.571, P < .001
Probability of AI in patients with cortisol 5-11 µg/dL
- DHEAS-Index >1
- 5%
- DHEAS-Index <1
- 40%
Original publication
Development and validation of a sex- and age-adjusted dehydroepiandrosterone sulfate index for suspected adrenal insufficiency. Eur J Endocrinol. Published 13 August 2026. doi:10.
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