Cortisol, Free, Urine
Preferred screening test for Cushing syndrome
Diagnosis of pseudo-hyperaldosteronism due to excessive licorice consumption
This test has limited usefulness in the evaluation of adrenal insufficiency
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) 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.
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.
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
Use the factor below to convert from mcg/24 hours to nmol/24 hours:
Cortisol: mcg/24 hours x 2.76=nmol/24 hours (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/81035 Synthetic Glucocorticoid Screen, 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 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 test has limited usefulness in the evaluation of adrenal insufficiency.
This methodology (liquid chromatography-tandem mass spectrometry: LC-MS/MS) 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.
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 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