Urinary-free cortisol-based thresholds for differentiating ACTH-dependent Cushing: a Spanish validation study
Authors' conclusion
UFC × ULN thresholds reliably stratify the probability of EAS vs CD. Severe hypercortisolism and hypokalemia strongly predict EAS
Study context
- Population
- Patients with ACTH-dependent Cushing syndrome (CS) diagnosed and managed in tertiary referral centres, Spanish Cushing Registry
- Participants
- 269 patients
- Comparison
- Ectopic ACTH secretion (EAS) vs Cushing disease (CD) by urinary-free cortisol (UFC) × upper limit of normal (ULN) and LNSC × ULN
- EASn = 61
- CDn = 208reference
- Outcome
- Diagnostic accuracy of UFC × ULN and LNSC × ULN for discriminating EAS from CD (AUC, sensitivity, specificity, predictive value)
Methodological detailsmulticentre, retrospective, registry-based
- Multicentre
- Retrospective
- Registry-based
Performance
As reported in the abstract
Discrimination of EAS from CD
| Test or model | AUC | EAS identified | Specificity |
|---|---|---|---|
| UFC × ULN | 0.90 | ||
| LNSC × ULN | 0.92 | ||
| UFC ≥ 10 × ULN and LNSC ≥ 9 × ULN plus hypokalemia | 75% | 98% |
AUC
UFC × ULN0.90
LNSC × ULN0.92
UFC ≥ 10 × ULN and LNSC ≥ 9 × ULN plus hypokalemia— not stated in the abstract
EAS identified
UFC × ULN— not stated in the abstract
LNSC × ULN— not stated in the abstract
UFC ≥ 10 × ULN and LNSC ≥ 9 × ULN plus hypokalemia75%
Specificity
UFC × ULN— not stated in the abstract
LNSC × ULN— not stated in the abstract
UFC ≥ 10 × ULN and LNSC ≥ 9 × ULN plus hypokalemia98%
- Patients with UFC ≥ 10 × ULN who had EAS
- 40.5%
Further findings
Age
P < 0.001
Original publication
Urinary-free cortisol-based thresholds for differentiating ACTH-dependent Cushing: a Spanish validation study. J Clin Endocrinol Metab. Published 30 April 2026. doi:10.
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