What this test measures
24-hour urinary free cortisol (UFC) measures the total amount of unbound (free, biologically active) cortisol filtered into urine over a full day. Because the kidney filters only free cortisol, UFC reflects the integrated daily cortisol production — unaffected by the diurnal rhythm and binding-protein changes that complicate serum cortisol interpretation.
The test requires a complete 24-hour urine collection — start by discarding the first morning urine, then collect every drop for the next 24 hours including the next morning's first urine.
Why it matters
UFC is one of the three first-line screening tests for Cushing's syndrome recommended by the Endocrine Society, alongside the overnight 1 mg dexamethasone suppression test and late-night salivary cortisol. Two abnormal first-line tests are usually required to confirm Cushing's.
UFC is particularly useful when other tests are confounded — for example, in patients on oestrogen pills (which raise binding proteins and serum cortisol without true Cushing's), or in shift workers with disturbed sleep (where salivary cortisol timing is unreliable). UFC is markedly raised in Cushing's syndrome (often 3–4× the upper limit), modestly raised in stress states and severe depression, and may be normal in mild or cyclic Cushing's — so a single normal UFC does not rule out the diagnosis.
How to prepare
You will be given a specific 24-hour urine collection bottle (sometimes with a preservative). Discard the first morning urine, note the time, then collect every drop of urine for the next 24 hours, including the next morning's first urine at the same start time. Keep the bottle refrigerated. Avoid contaminating with stool. Continue medications unless your doctor instructs otherwise. Avoid extreme exercise or stress on the collection day. Two separate 24-hour collections are usually recommended for confirmation.
Markers & reference ranges
Reference ranges below are typical adult values. Your lab's reported range may differ slightly based on the assay platform and patient demographics — always read your report against the range printed on it.
| Marker | Normal range | If low | If high |
|---|---|---|---|
| 24-hour Urinary Free Cortisol (µg/24 h)[1][2] | 4 – 50 µg/24 h (assay-dependent; many labs use < 50 or < 60) | Low UFC supports adrenal insufficiency in the right clinical context. Can also reflect incomplete collection — check urine creatinine to confirm completeness. | UFC > 3× upper limit is highly suggestive of Cushing's syndrome. Lower elevations can be seen in stress states (severe depression, alcoholism, anorexia, severe illness — "pseudo-Cushing's"), pregnancy, polycystic ovary syndrome, and high water intake. Two separate raised UFC values are usually required for diagnosis; very high values (> 4× upper limit) are essentially diagnostic. |
UFC — interpretation
| UFC (µg/24h) | Interpretation | Action |
|---|---|---|
| < 50 | Normal | Cushing's very unlikely; consider other diagnoses |
| 50 – 150 | Mildly raised | Repeat; consider pseudo-Cushing's (depression, alcoholism, severe illness) |
| 150 – 500 | Moderately raised | Strong suspicion — confirm with 2nd test + workup |
| > 500 (> 4× upper limit) | Markedly raised | Essentially diagnostic — proceed to localisation |
| Cyclic Cushing's | Variable | Multiple collections over time may be needed |
Frequently asked questions
How do I do a 24-hour urine collection correctly?
Discard the first morning urine, note the time, then collect every drop of urine for the next 24 hours — including the next morning's first urine. Store the bottle refrigerated. A complete collection is crucial; an incomplete collection gives a falsely low result.
What if I miss a urine sample?
Missing one urine in the 24 hours can give a falsely low result. If you miss one, the cleanest option is to restart the collection on a fresh day.
Why are multiple tests for Cushing's used?
No single test is both sensitive and specific. The Endocrine Society guideline recommends two of three first-line tests be abnormal (UFC, overnight 1 mg dexamethasone suppression, or late-night salivary cortisol) before pursuing the cause.
What can cause a falsely raised UFC?
Severe stress, depression, alcoholism, anorexia, severe illness, pregnancy, PCOS, excessive water intake (> 5 L/day), and high-dose carbamazepine. These are collectively called "pseudo-Cushing's" — UFC is mildly raised but the patient does not have true disease.
Can I do the test at home?
Yes — Zelnoo provides a 24-hour collection bottle at home; you collect urine through the day, store it refrigerated, and the bottle is collected the next morning for laboratory analysis.
Will my medications affect the result?
Yes. Glucocorticoids (oral, inhaled, topical, joint) and many other drugs affect cortisol metabolism. Tell your doctor about everything you take — they will judge what (if anything) needs to be paused.
How often should this be repeated?
Usually two collections for diagnosis. After Cushing's treatment (surgery, radiation), UFC is used to monitor remission and recurrence.
Related Hormones / Endocrine tests
Tests commonly ordered alongside URINARY CORTISOL, or that help interpret an unexpected result.
Sources & references
- Endocrine Society — Cushing's Syndrome Clinical Practice Guideline · accessed 2026-05-30T00:00:00.000Z
- NIH MedlinePlus — Cortisol Test · accessed 2026-05-30T00:00:00.000Z
- NCBI StatPearls — Cushing Syndrome · accessed 2026-05-30T00:00:00.000Z
- Mayo Clinic Laboratories — 24-hour Urinary Free Cortisol · accessed 2026-05-30T00:00:00.000Z
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