Test Id : COCOU

24-Hour volume (in milliliters) is required.

Supplies: Urine Tubes, 10-mL (T068)

Submission Container/Tube: Plastic, urine tube (T068)

Specimen Volume: 5 mL

Collection Instructions:

1. Add 10 g of boric acid as preservative at start of collection.

2. Collect urine for a full 24 hours (required) and record the total volume.

Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens for multiple collections.

• Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens

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

3 mL

Screening test for Cushing syndrome (hypercortisolism)

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.

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.

CORTISOL

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

> or =18 years: 3.5-45 mcg/24 h

CORTISONE

0-2 years: not established

3-8 years: 5.5-41 mcg/24 h

9-12 years: 9.9-73 mcg/24 h

13-17 years: 15-108 mcg/24 h

> or =18 years: 17-129 mcg/24 h

Use the factors below to convert each analyte from mcg/24 h to nmol/24 h:

Conversion factors

Cortisol: mcg/24 hours x 2.76=nmol/24 h (molecular weight=362.5)

Cortisone: mcg/24 hours x 2.78=nmol/24 h (molecular weight=360)

For International System of Units (SI) conversion for Reference Values, see www.mayocliniclabs.com/order-tests/si-unit-conversion.html

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) 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 (call 800-533-1710).

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 hydroxy steroid dehydrogenase 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.

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) 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.

1. 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

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 Endo Metab 1997;82(1):151-155 3. Eisenhofer G, Grebe S, Cheung NK V. Monoamine-producing tumors. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:1421

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, Cortisone and d4-cortisol are extracted from the specimens using online turbulent flow high-performance liquid chromatography extraction.(Unpublished Mayo method)

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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.

82530-Cortisol; free

82542