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HelpMayo Test ID CCFR Cortisol/Cortisone, Free, Random, Urine
Specimen Required
Supplies: Urine tube, 10 mL (T068)
Collection Container/Tube: Clean, plastic urine container with no metal cap or glued insert
Submission Container/Tube: Plastic, 10-mL urine tube or clean, plastic aliquot container with no metal cap or glued insert
Specimen Volume: 10 mL
Collection Instructions: Collect a random urine specimen.
Useful For
Investigating suspected Cushing syndrome (hypercortisolism), when a 24-hour collection is prohibitive (ie, pediatric patients).
Assisting in diagnosing acquired or inherited abnormalities of 11-beta-hydroxy steroid dehydrogenase (cortisol to cortisone ratio)
Diagnosis of pseudohyperaldosteronism due to excessive licorice consumption
This test has limited usefulness in the evaluation of adrenal insufficiency.
This test is not useful for evaluation of hypocorticalism.
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| COCOR | Cortisol, Random, U | No | Yes |
| CRETR | Creatinine, Random, U | Yes, (order RCTUR) | Yes |
Method Name
COCOR: Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
CRETR: Enzymatic Colorimetric Assay
Reporting Name
Cortisol/Cortisone, Free, Random, USpecimen Type
UrineSpecimen Minimum Volume
5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Urine | Refrigerated (preferred) | 14 days | |
| Frozen | 28 days | ||
| Ambient | 72 hours |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.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. It 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
CORTISOL
Males
0-2 years: 3.0-120 mcg/g creatinine
3-8 years: 2.2-89 mcg/g creatinine
9-12 years: 1.4-56 mcg/g creatinine
13-17 years: 1.0-42 mcg/g creatinine
≥18 years: 1.0-119 mcg/g creatinine
Females
0-2 years: 3.0-120 mcg/g creatinine
3-8 years: 2.2-89 mcg/g creatinine
9-12 years: 1.4-56 mcg/g creatinine
13-17 years: 1.0-42 mcg/g creatinine
≥18 years: 0.7-85 mcg/g creatinine
CORTISONE
0-2 years: 25-477 mcg/g creatinine
3-8 years: 11-211 mcg/g creatinine
9-12 years: 5.8-109 mcg/g creatinine
13-17 years: 5.4-102 mcg/g creatinine
18-29 years: 5.7-153 mcg/g creatinine
30-39 years: 6.6-176 mcg/g creatinine
40-49 years: 7.6-203 mcg/g creatinine
50-59 years: 8.8-234 mcg/g creatinine
60-69 years: 10-270 mcg/g creatinine
≥70 years: 12-311 mcg/g creatinine
Use the conversion factors below to convert each analyte from mcg/g creatinine to nmol/mol creatinine:
Conversion factors
Cortisol: mcg/g creatinine x 312=nmol/mol creatinine
Cortisone: mcg/g creatinine x 314=nmol/mol creatinine
Cortisol molecular weight=362.5
Cortisone molecular weight=360.4
Creatinine molecular weight=113.12
Interpretation
Most patients with Cushing syndrome have increased urinary excretion of cortisol and/or cortisone. Further studies, including suppression or stimulation tests, measurement of serum corticotrophin 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 (SGSU / Synthetic Glucocorticoid Screen, Random, Urine).
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.
Patients with 11-beta HSD deficiency may have cortisone to cortisol ratios less than 1, whereas a ratio of 2 or 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 less than 1.
Cautions
Random urine cortisol results are less reliable than results obtained from properly collected and complete 24-hour urine specimens, which are not affected by diurnal variations in cortisol levels.
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.
Liquid chromatography tandem mass spectrometry methodology eliminates analytical interferences including carbamazepine (Tegretol) and synthetic corticosteroids.
Random urine specimens may yield falsely elevated values when patients have a high urinary output.
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.
When N-acetylcysteine is administered at levels sufficient to act as an antidote for the treatment of acetaminophen overdose, it may lead to falsely decreased creatinine results.
Clinical Reference
1. 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
2. Findling JW, Raff H. Diagnosis and differential diagnosis of Cushing's syndrome. Endocrinol Metab Clin North Am. 2001;30:729-747
3. Boscaro M, Barzon L, Fallo F, Sonino N. Cushing's syndrome. Lancet. 2001;357:783-791
4. Suzuki S, Minamidate T, Shiga A, et al. Steroid metabolites for diagnosing and predicting clinicopathological features in cortisol-producing adrenocortical carcinoma. BMC Endocr Disord. 2020;20(1):173. doi:10.1186/s12902-020-00652-y
Method Description
Cortisol and Cortisone:
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. Deuterated cortisol (d4-cortisol, d7-cortisone) is added to a 0.1 mL sample as an internal standard. Cortisol.(Unpublished Mayo Method)
Creatinine:
The enzymatic method is based on the determination of sarcosine from creatinine with the aid of creatininase, creatinase, and sarcosine oxidase. The liberated hydrogen peroxide is measured via a modified Trinder reaction using a colorimetric indicator. Optimization of the buffer system and the colorimetric indicator enables the creatinine concentration to be quantified both precisely and specifically.(Package insert: Creatinine plus ver 2. Roche Diagnostics; V15.0, 03/2019)
Day(s) Performed
Monday through Friday
Report Available
2 to 6 daysSpecimen Retention Time
14 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
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
82542
82530 - Cortisol
82570 - Creatinine
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CCFR | Cortisol/Cortisone, Free, Random, U | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 10328 | Cortisol/Creatinine Ratio | 11155-9 |
| CRETR | Creatinine, Random, U | 2161-8 |
| 10329 | Cortisone/Creatinine Ratio | 30511-0 |