The conundrum of differentiating Cushing’s syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis
Authors' conclusion
Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.
Study context
- Population
- Patients with confirmed hypercortisolemia: Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism vs non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome); articles through March 202224 articles
- Participants
- 1,900 patients
- Comparison
- Dex-CRH test vs desmopressin stimulation test vs midnight serum cortisol (MSC) vs late-night salivary cortisol (LNSC) to distinguish CS from NNH
- Outcome
- Diagnostic accuracy to distinguish CS from NNH
Methodological detailsPRISMA-DTA, independent duplicate review
- PRISMA-DTA
- Independent duplicate review
Pooled result
As reported in the abstract
Pooled diagnostic accuracy for CS vs NNH
| Group | AUC (summary ROC) | Sensitivity | Specificity |
|---|---|---|---|
| Dex-CRH | 0.949 | 91% (95%CI 87-94%; I2 0%) | 82% (73-88%; I2 50%) |
| Desmopressin test | 0.936 | 86% (81-90%; I2 28%) | 90% (84-94%; I2 15%) |
| MSC | 0.942 | 91% (85-94%; I2 66%) | 81% (70-89%; I2 71%) |
| LNSC | 0.950 | 80% (67-89%; I2 57%) | 90% (84-93%; I2 21%) |
AUC (summary ROC)
Dex-CRH0.949
Desmopressin test0.936
MSC0.942
LNSC0.950
Sensitivity
Dex-CRH91% (95%CI 87-94%; I2 0%)
Desmopressin test86% (81-90%; I2 28%)
MSC91% (85-94%; I2 66%)
LNSC80% (67-89%; I2 57%)
Specificity
Dex-CRH82% (73-88%; I2 50%)
Desmopressin test90% (84-94%; I2 15%)
MSC81% (70-89%; I2 71%)
LNSC90% (84-93%; I2 21%)
Further pooled results
- The overall risk of studies bias was moderate
Original publication
The conundrum of differentiating Cushing’s syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis. Pituitary. Published 18 June 2024. doi:10.
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