Cortisol, Free, 24-Hour Urine

Test Code

14534

CPT Codes
82530, 82570

Includes

Creatinine

CPT code 81050 may be added at an additional charge for volume measurement

Preferred Specimen

2 mL of an unpreserved 24-hour urine collection submitted in a leak-proof urine container

Minimum Volume

0.5 mL

Other Acceptable Specimens

Preserved urine collected in 10 gram boric acid, or 10 mL concentrated glacial acetic acid or 25 mL 6N HCl

Instructions

Keep urine refrigerated during collection, if preservative is not used.
Record 24-hour urine volume on test request form and urine vial.

Note: Reference ranges do not apply to random urine samples.

Transport Container

Plastic urine container

Transport Temperature

Refrigerated (cold packs)

Specimen Stability

Room temperature: 14 days
Refrigerated: 21 days
Frozen: 3 months

Methodology
Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS)

Setup Schedule

Set up: Mon-Fri; Report available: 2-6 days

Reference Range

Cortisol, Free, 24-Hr Urine

Adult	4.0-50.0 mcg/24 hrs
Pediatric
1-4 Years	0.9-8.2 mcg/24 hrs
5-9 Years	1.0-30.0 mcg/24 hrs
10-13 Years	1.0-45.0 mcg/24 hrs
14-17 Years	3.0-55.0 mcg/24 hrs

Cortisol, Free, Urine

Adult

3.1-42.3 mcg/g creat

Creatinine, 24-Hour Urine

<3 Years	Not established
3-8 Years	0.10-0.80 g/24 hours
9-12 Years	0.20-1.40 g/24 hours
13-17 Years	0.40-1.90 g/24 hours
>17 Years	0.50-2.15 g/24 hours

Clinical Significance

This urinary free cortisol (UFC) test, performed with a 24-hour urine specimen, is one of the preferred tests for screening for and diagnosing Cushing syndrome. This test may also be used to monitor for recurrence of Cushing disease [1]. In addition, when used in conjunction with the measurement of 24-hour urine cortisone, this test may help identify disorders caused by impaired activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), such as apparent mineralocorticoid excess (AME) syndrome [2].

UFC level is independent of corticosteroid-binding globulin and albumin levels; thus, UFC level can demonstrate increased bioavailable cortisol in patients with endogenous Cushing syndrome [1]. A UFC test with 24-hour urine specimen also has the advantage of averaging circadian and ultradian variations of cortisol secretion. An elevated UFC level may provide initial evidence for Cushing syndrome. Two or more positive results of UFC tests may establish the diagnosis of Cushing syndrome if non-neoplastic hypercortisolism (pseudo-Cushing syndrome) is excluded [1].

A late-night salivary cortisol (LNSC) test or dexamethasone suppression test (DST) can also be used to diagnose Cushing syndrome or monitor for Cushing disease. Choice of test should be based on clinical scenario [1]. When monitoring for recurrence of Cushing disease, UFC levels usually become abnormal after LNSC tests or DSTs do [1].

UFC testing is not recommended for screening for Cushing syndrome in individuals with impaired kidney function or polyuria [1]. Non-neoplastic hypercortisolism caused by obesity, psychiatric disorders, alcohol use disorder, and polycystic ovary syndrome may increase UFC levels.

In patients with AME syndrome, deficiency of 11beta-HSD2 impairs the deactivation of cortisol to cortisone. Similarly, ingestion of certain compounds that inhibit 11beta-HSD2 activity, such as glycyrrhetinic acid (in licorice), carbenoxolone, and phthalates, may also reduce the conversion of cortisol to cortisone. Therefore, a high cortisol-to-cortisone ratio measured in 24-hour urine may help identify disorders caused by impaired activity of 11beta-HSD2 [2, 3].

The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.

Reference
1. Fleseriu M, et al. Lancet Diabetes Endocrinol. 2021;9(12):847-875.
2. Young WF, Jr., et al. Endocrine Reviews. 2017;38(2):103-122.
3. Carvajal CA, et al. J Clin Endocrinol Metab. 2020;105(4):dgz315.

The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. Any Profile/panel component may be ordered separately. Reflex tests are performed at an additional charge.