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Test Code CORTU Cortisol, Free, 24 Hour, Urine

Reporting Name

Cortisol, Free, U

Useful 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.

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Urine


Necessary 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

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CORTU Cortisol, Free, U 43126-2

 

Result ID Test Result Name Result LOINC Value
8546 Cortisol, U 14158-0
TM93 Collection Duration (h) 13362-9
VL47 Volume (mL) 3167-4

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.

Supportive Data

In Mayo's reference value study, gender was found to significantly influence cortisol values (P value=0.001). However, while this was statistically significant, gender explained only 6% of the variability in cortisol normal ranges and, therefore, was not considered to have a clinically significant impact on cortisol reference 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 days

Specimen Retention Time

14 days

Reject Due To

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Method Name

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

Secondary ID

8546

Urine Preservative Collection Options

Note: The addition of preservative must occur prior to the start of the collection or application of temperature controls must occur during collection.

Ambient (no additive)

No

Refrigerate (no additive)

OK

Frozen (no additive)

OK

50% Acetic Acid

OK

Boric Acid

Preferred

Diazolidinyl Urea

No

6M Hydrochloric Acid

No

6M Nitric Acid

No

Sodium Carbonate

No

Thymol

No

Toluene

No