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.
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Cortisol Free Urine
Free Urinary Cortisol
Urinary Free Cortisol
Urine
24-Hour volume (in milliliters) is required.
Question ID | Description | Answers |
---|---|---|
TM93 | Collection Duration | |
VL47 | Urine Volume |
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.
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 |
3 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Urine | Refrigerated (preferred) | 14 days | |
Frozen | 28 days | ||
Ambient | 7 days |
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.
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.
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.
0-2 years: not established
3-8 years: 1.4-20 mcg/24 hr
9-12 years: 2.6-37 mcg/24 hr
13-17 years: 4.0-56 mcg/24 hr
> or =18 years: 3.5-45 mcg/24 hr
Use the factor below to convert from mcg/24 hr to nmol/24 hr:
Conversion factor
Cortisol: mcg/24 hours x 2.76=nmol/24 hr (molecular weight=362.5)
Most patients with Cushing syndrome have increased 24-hour urinary excretion of cortisol. 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 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.
Acute stress (including hospitalization and surgery),
This test has limited usefulness in the evaluation of adrenal
This methodology (liquid chromatography-tandem mass spectrometry
Renal disease (decreased excretion) may cause falsely low
Improper collection may alter results. For example, a missed morning
Twenty-four hour urinary free cortisol values may be elevated to
Patients with exogenous Cushing syndrome caused by ingestion
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.
1. Findling JW, Raff H. Diagnosis and differential diagnosis of Cushing's syndrome. Endocrinol Metab Clin North Am. 2001;30(3):729-747
2. Boscaro M, Barzon L, Fallo F, Sonino N. Cushing's syndrome. Lancet. 2001;357(9258):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(9):1511-1519
4. 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. pp 1421
5. Luo A, El Gierari ETM, Nally LM, et al. Clinical utility of an ultrasensitive urinary free cortisol assay by tandem mass spectrometry. Steroids. 2019;146:65-69. doi:10.1016/j.steroids.2019.03.014
The cortisol and cortisone are extracted from the resulting supernatant by an online extraction utilizing high-throughput liquid chromatography (HTLC). 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 HPLC extraction. (Unpublished Mayo Method)
Monday through Friday
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
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CORTU | Cortisol, Free, U | 43126-2 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
8546 | Cortisol, U | 14158-0 |
TM93 | Collection Duration | 13362-9 |
VL47 | Urine Volume | 3167-4 |