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HelpTest ID CORTU Cortisol, Free, 24 Hour, Urine
Reporting Name
Cortisol, Free, UUseful For
Preferred screening test for Cushing syndrome
Diagnosis of pseudo-hyperaldosteronism due to excessive licorice consumption
Test may not be useful in the evaluation of adrenal insufficiency.
Specimen Type
UrineNecessary Information
24-Hour volume (in milliliters) is required.
Specimen Required
Supplies: Urine Tubes, 10-mL (T068)
Submission Container/Tube: Plastic urine tube
Specimen Volume: 5 mL
Collection Instructions:
1. Collect urine for 24 hours.
2. Add 10 g of boric acid as preservative at start of collection.
Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens for multiple collections.
Specimen Minimum Volume
3 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Urine | Refrigerated (preferred) | 14 days | |
| Frozen | 28 days | ||
| Ambient | 7 days |
Reference Values
0-2 years: Not established
3-8 years: 1.4-20 mcg/24 h
9-12 years: 2.6-37 mcg/24 h
13-17 years: 4.0-56 mcg/24 h
≥18 years: 3.5-45 mcg/24 h
Use the factor below to convert from mcg/24 hr to nmol/24 hr:
Conversion factor
Cortisol: mcg/24 h x 2.76=nmol/24 hr (molecular weight=362.5)
For International System of Units (SI) conversion for Reference Values, see www.mayocliniclabs.com/order-tests/si-unit-conversion.html.
Day(s) Performed
Monday through Friday
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
82530
Clinical Information
Cortisol is a steroid hormone synthesized from cholesterol by a multienzyme cascade in the adrenal glands. It is the main glucocorticoid in humans and acts as a gene transcription factor influencing a multitude of cellular responses in virtually all tissues. Cortisol plays a critical role in glucose metabolism, maintenance of vascular tone, immune response regulation, and in the body's response to stress. Its production is under hypothalamic-pituitary feedback control.
Only a small percentage of circulating cortisol is biologically active (free), with the majority of cortisol inactive (protein bound). As plasma cortisol values increase, free cortisol (ie, unconjugated cortisol or hydrocortisone) increases and is filtered through the glomerulus. Urinary free cortisol (UFC) in the urine correlates well with the concentration of plasma free cortisol. UFC represents excretion of the circulating, biologically active, free cortisol that is responsible for the signs and symptoms of hypercortisolism.
Urinary free cortisol is a sensitive test for the various types of adrenocortical dysfunction, particularly hypercortisolism (Cushing syndrome). A measurement of 24-hour UFC excretion, by liquid chromatography tandem mass spectrometry (LC-MS/MS), is the preferred screening test for Cushing syndrome. LC-MS/MS methodology eliminates analytical interferences including carbamazepine (Tegretol) and synthetic corticosteroids, which can affect immunoassay-based cortisol results.
Interpretation
Most patients with Cushing syndrome have increased 24-hour urinary excretion of cortisol. Further studies, including suppression or stimulation tests, measurement of serum corticotropin concentrations, and imaging are usually necessary to confirm the diagnosis and determine the etiology.
Values in the normal range may occur in patients with mild Cushing syndrome or with periodic hormonogenesis. In these cases, continuing follow-up and repeat testing are necessary to confirm the diagnosis.
Patients with Cushing syndrome due to intake of synthetic glucocorticoids should have suppressed cortisol. In these circumstances a synthetic glucocorticoid screen might be ordered (SGSU / Synthetic Glucocorticoid Screen, Random, Urine).
Suppressed cortisol values may also be observed in primary adrenal insufficiency and hypopituitarism. However, many normal individuals may also exhibit a very low 24-hour urinary cortisol excretion with considerable overlap with the values observed in pathological hypocorticalism. Therefore, without other tests, 24-hour urinary cortisol measurements cannot be relied upon for the diagnosis of hypocorticalism.
Cautions
Acute stress (including hospitalization and surgery), alcoholism, depression, and many drugs (eg, exogenous cortisone, anticonvulsants) can obliterate normal diurnal variation, affect response to suppression/stimulation tests, and increase baseline levels.
This test has limited usefulness in the evaluation of adrenal insufficiency.
This methodology (liquid chromatography tandem mass spectrometry) eliminates analytical interferences including carbamazepine (Tegretol) and synthetic corticosteroids.
Renal disease (decreased excretion) may cause falsely low 24-hour urinary free cortisol values.
Improper collection may alter results. For example, a missed morning collection may result in false-negative tests; an extra morning collection (ie, >24 hours) may give false-positive results.
Twenty-four-hour urinary free cortisol values may be elevated to twice the upper limit of the normal range during pregnancy.
Patients with exogenous Cushing syndrome caused by ingestion of hydrocortisone will not have suppressed cortisol values.
Clinical Reference
1. Eisenhofer G, Grebe S, Cheung N-K V.Monoamine-Producing Tumors. In: Rafai N, Horvath AR, Witter CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier, 2018: 1421
2. Lin CL, Wu TJ, Machacek DA, Jiang NS, Kao PC. Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 1997;82(1):151-155
3. Dodds HM, Taylor PJ, Cannell GR, Pond SM. A high-performance liquid chromatography-electrospray-tandem mass spectrometry analysis of cortisol and metabolites in placental perfusate. Anal Biochem. 1997;247(2):342-347. doi:10.1006/abio.1997.2074
Method Description
The cortisol and cortisone are extracted from the resulting supernatant by an online extraction utilizing high-throughput liquid chromatography. This is followed by conventional liquid chromatography and analysis on a tandem mass spectrometer equipped with a heated nebulizer ion source (APCI). Deuterated cortisol (d4-cortisol, d7-cortisone) is added to a 0.1 mL sample as an internal standard. Cortisol, Cortisone and d4-cortisol are extracted from the specimens using online turbulent flow high-performance liquid chromatography extraction.(Unpublished Mayo method)
Report Available
2 to 6 daysReject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.NY State Approved
YesMethod Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)