Test ID: COCOU
Cortisol/Cortisone, Free, Urine
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Screening test for Cushing syndrome
Assisting in diagnosing acquired or inherited abnormalities of 11-beta-hydroxy steroid dehydrogenase (cortisol to cortisone ratio)
Diagnosis of pseudo-hyperaldosteronism due to excessive licorice consumption
This test has limited usefulness in the evaluation of adrenal insufficiency.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
17-Ketogenic Steroid
Cortisol
Cortisol, Free
Cortisol/Cortisone, Free
Cortison
Cortisone
Free Urinary Cortisol
Urinary Free Cortisol
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Plastic, 10-mL urine tube (Supply T068)
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:
1. 24-Hour volume is required.
2. See Urine Preservatives in Special Instructions for multiple collections.
Urine Preservative Collection Options
| Ambient | No |
| Refrigerated | Yes |
| Frozen | Yes |
| 6N HCl | No |
| 50% Acetic Acid | Yes |
| Na2CO3 | Yes |
| Toluene | Yes |
| 6N HNO3 | No |
| Boric Acid | Preferred |
| Thymol | Yes |
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Urine | Refrigerated (preferred) | 7 days |
| Frozen | 14 days | |
| Ambient | 7 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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) 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. UFC 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.
Cortisone, a downstream metabolite of cortisol, provides an additional variable to assist in the diagnosis of various adrenal disorders, including abnormalities of 11-beta-hydroxy steroid dehydrogenase (11-beta HSD), the enzyme that converts cortisol to cortisone. Deficiency of 11-beta HSD results in a state of mineralocorticoid excess because cortisol (but not cortisone) acts as a mineralocorticoid receptor agonist. Licorice (active component glycyrrhetinic acid) inhibits 11-beta HSD and excess consumption can result in similar changes.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
CORTISOL
0-2 years: not established
3-8 years: 1.4-20 mcg/24 hours
9-12 years: 2.6-37 mcg/24 hours
13-17 years: 4.0-56 mcg/24 hours
> or =18 years: 3.5-45 mcg/24 hours
CORTISONE
0-2 years: not established
3-8 years: 5.5-41 mcg/24 hours
9-12 years: 9.9-73 mcg/24 hours
13-17 years: 15-108 mcg/24 hours
> or =18 years: 17-129 mcg/24 hours
Use the factors below to convert each analyte from mcg/24 hours to nmol/24 hours:
Conversion factors
Cortisol: mcg/24 hours x 2.76=nmol/24 hours (molecular weight=362.5)
Cortisone: mcg/24 hours x 2.78=nmol/24 hours (molecular weight=360)
Interpretation Provides information to assist in interpretation of the test results
Most patients with Cushing syndrome have increased 24-hour urinary excretion of cortisol and/or cortisone. Further studies, including suppression or stimulation tests, measurement of serum corticotropin (adrenocorticotropic hormone [ACTH]) 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 both suppressed cortisol and cortisone. In these circumstances a synthetic glucocorticoid screen might be ordered (ZW14/8123 Miscellaneous Endocrine Testing).
Suppressed cortisol and cortisone values may also be observed in primary adrenal insufficiency and hypopituitarism. However, random urine specimens are not useful for evaluation of hypocorticalism. Further, many normal individuals also may 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.
Patients with 11-beta HSD deficiency may have cortisone to cortisol ratios <1, whereas a ratio of 2:1 to 3:1 is seen in normal patients. Excessive licorice consumption and use of carbenoxolone, a synthetic derivative of glycyrrhizinic acid used to treat gastroesophageal reflux disease, also may suppress the ratio to <1.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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 methodology (liquid chromatography-tandem mass spectrometry [LC-MS/MS]) eliminates analytical interferences including carbamazepine (Tegretol) and synthetic corticosteroids.
This test has limited usefulness in the evaluation of adrenal insufficiency.
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.
Renal disease (decreased clearance) may cause falsely low values.
Values may be elevated to twice normal in pregnancy.
Patients with exogenous Cushing syndrome caused by ingestion of hydrocortisone will not have suppressed cortisol and cortisone values.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's syndrome. Endocrinol Metab Clin North Am 2001;30:729-747
2. Boscaro M, Barzon L, Fallo F, Sonino N: Cushing's syndrome. Lancet 2001;357:783-791
3. Taylor RL, Machacek D, Singh RJ: Validation of a high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and cortisone. Clin Chem 2002;48:1511-1519
Method Description Describes how the test is performed and provides a method-specific reference
Deuterated cortisol (d3-cortisol) is added to a 0.1-mL urine specimen as an internal standard. Cortisol, cortisone, and d3-cortisol are extracted from the specimens using online turbulent-flow HPLC and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using multiple-reaction monitoring in positive mode. The following ion pairs are used for analysis: Cortisol (363.0/121.1); Cortisone (361.0/163.0); d3-Cortisol (366.0/121.2). A calibration curve, generated from stripped urine spiked standards, is included with each batch of patient specimens. (Taylor RL, Machacek DA, Singh RJ: Validation of a high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and cortisone. Clin Chem 2002;48:1511-1519)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Saturday: 1 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
82530-Cortisol; free
83789-Quantitative, each specimen
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 8546 | Cortisol, U | 14158-0 |
| 10327 | Cortisone, U | 14044-2 |
| TM93 | Collection Duration | 13362-9 |
| VL47 | Urine Volume | 19153-6 |
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