Big data determination and validation of reference range for 24 hour urine cortisol by LCMS/MS
Authors' conclusion
We used mass population data, where the prevalence of CS was likely very rare, plus a carefully phenotyped sample where CS was considered but excluded, to derive a validated reference interval for 24-h UFC by mass spectrometry in populations that reflect real-world use of the test. Given the highly skewed upper tail of the population distribution, it is probable that high test specificity for CS will require multimodality diagnostic confirmation.
Study context
- Population
- Patients with potential features of Cushing syndrome (CS), Canada
- Participants
- 4,830 vs 120
- Exposure
- Retrospective non-CS population vs prospective patients with CS excluded
- Retrospectiven = 4,830
- Prospectiven = 120
- Outcome
- Middle 95%ile reference interval for 24-h UFC by mass spectrometry
Methodological detailsrefineR reference interval algorithm, government health system and tertiary endocrinology clinic
- refineR reference interval algorithm
- Government health system and tertiary endocrinology clinic
Main finding
As reported in the abstract
Adult male urine-free cortisol (UFC) upper reference limit
238 nmol/day
86.3 μg/day
Female UFC upper reference limit
147 nmol/day
53.3 μg/day
Volume-corrected upper limit, male
89 nmol/L
32.3 μg/L
Volume-corrected upper limit, female
91 nmol/L
32.9 μg/L
Observational data: associations, not effects.
Further findings
| Outcome | P value |
|---|---|
| Volume-corrected UFC distributions, prospective vs retrospectiveNo significant difference | P = 0.09 |
Correlation of UFC and 24-h urine volume
- R
- 0.28, P < .0001
UFC distribution
- Highly skewed, with strong sex interaction
- P < 0.0001
Results flagged high, applied to both populations
- Proportion flagged high; most expected to be nonneoplastic (pseudo)Cushing's
- between 3% and 8%
Original publication
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