Test Catalog

Test Id : CORTO

Cortisol, Free and Total, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Assessment of cortisol status in cases where there is known or a suspected abnormality in cortisol-binding proteins or albumin

 

Assessment of adrenal function in the critically ill or stressed patient, thus preventing unnecessary use of glucocorticoid therapy

 

Second-order testing when cortisol measurement by immunoassay (eg, CORT / Cortisol, Serum) gives results that are not consistent with clinical symptoms, or if patients are known to, or suspected of, taking exogenous synthetic steroids

 

An adjunct in the differential diagnosis of primary and secondary adrenal insufficiency

 

An adjunct in the differential diagnosis of Cushing syndrome

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
CINP Cortisol, S, LC-MS/MS Yes Yes
CORTF Cortisol, Free, S Yes Yes

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Cortisol, Free and Total, S

Aliases
Lists additional common names for a test, as an aid in searching

Compound F

Corticosteroids

Cortisol

Cortrosyn Stimulation Test

Free Cortisol

FCORT

CORTO

Specimen Type
Describes the specimen type validated for testing

Serum Red

Ordering Guidance

For confirming the presence of synthetic steroids, order SGSS / Synthetic Glucocorticoid Screen, Serum.

 

Cushing syndrome is characterized by increased serum cortisol levels. However, the 24-hour urinary free cortisol excretion is the preferred screening test for Cushing syndrome, specifically CORTU / Cortisol, Free, 24 Hour, Urine that utilizes liquid chromatography-tandem mass spectrometry. A normal result makes the diagnosis unlikely.

 

The most common cause of increased plasma cortisol levels in women is a high circulating concentration of estrogen (ie, estrogen therapy, pregnancy) resulting in increased concentration of corticosteroid-binding globulin. This does not result in an increase in the free, bioactive cortisol fraction. For this reason, measurement of 24-hour urinary free cortisol (CORTU / Cortisol, Free, 24 Hour, Urine) or demonstration of absent diurnal variation (ie, by midnight salivary cortisol measurement SALCT / Cortisol, Saliva) are the preferred means of diagnosing spontaneous Cushing syndrome.

 

This test is not recommended for evaluating response to metyrapone; DCORT / 11-Deoxycortisol, Serum is more reliable.

 

A low plasma cortisol level does not give conclusive indication of congenital adrenal hyperplasia. DCORT / 11-Deoxycortisol, Serum; OHPG / 17-Hydroxyprogesterone, Serum; and DHEA_ / Dehydroepiandrosterone (DHEA), Serum provide a more accurate and specific determination of the enzyme deficiency.

Necessary Information

Include time of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube: Red top (serum gel/SST are not acceptable)

Specimen Volume: 1.85 mL

Collection Instructions: Morning (8 a.m.) specimens are preferred. The 8 a.m. cortisol can be referred to as the a.m. cortisol and can be collected anywhere between 6 a.m. and 10:30 a.m. in the morning.

Additional Information: If multiple specimens are collected, send separate order for each specimen.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1.2 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 28 days
Ambient 28 days
Frozen 28 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Assessment of cortisol status in cases where there is known or a suspected abnormality in cortisol-binding proteins or albumin

 

Assessment of adrenal function in the critically ill or stressed patient, thus preventing unnecessary use of glucocorticoid therapy

 

Second-order testing when cortisol measurement by immunoassay (eg, CORT / Cortisol, Serum) gives results that are not consistent with clinical symptoms, or if patients are known to, or suspected of, taking exogenous synthetic steroids

 

An adjunct in the differential diagnosis of primary and secondary adrenal insufficiency

 

An adjunct in the differential diagnosis of Cushing syndrome

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Cortisol, the main glucocorticoid (representing 75%-95% of the plasma corticoids), plays a critical role in glucose metabolism and in the body's response to stress. Both hypercortisolism (Cushing disease) and hypocortisolism (Addison disease) can cause disease. Cortisol is also used to treat skin disease, allergic disorders, respiratory system disease, inflammatory disorders, and nephrotic syndrome.

 

Cortisol levels are regulated by adrenocorticotropic hormone (ACTH), which is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH). CRH is released in a cyclic fashion by the hypothalamus, resulting in diurnal peaks (6 a.m.-8 a.m.) and troughs (11 p.m.) in plasma ACTH and cortisol levels.

 

The majority of cortisol circulates bound to corticosteroid-binding globulin (CBG) and albumin. Normally, less than 5% of circulating cortisol is free (unbound). Only free cortisol can access the enzyme transporters in liver, kidney, and other tissues that mediate metabolic and excretory clearance.

 

Historically, measurements of free cortisol have been achieved from indirect means using a ratio known as the free cortisol index. This measurement takes into account the amount of total cortisol and CBG to give a percentage and, ultimately, absolute value of free cortisol. These methods do not take into account the possibility variations in albumin levels. These calculations also rely on CBG, which can be lowered in critically ill patients despite normal adrenal function. Equilibrium dialysis best serves to separate free from bound cortisol without disrupting the bound fraction.

 

Pathological hypercortisolism due to endogenous or exogenous glucocorticoids is termed Cushing syndrome. Signs and symptoms of pathological hypercortisolism may include central obesity, hypertension, hyperglycemia, hirsutism, muscle weakness, and osteoporosis. However, these symptoms and signs are not specific for pathological hypercortisolism. The majority of individuals with some or all of the symptoms and signs will not suffer from Cushing syndrome.

 

When Cushing syndrome is present, the most common cause is iatrogenic, due to repeated or prolonged administration of, mostly, synthetic corticosteroids. Spontaneous Cushing syndrome is less common and results from either primary adrenal disease (adenoma, carcinoma, or nodular hyperplasia) or an excess of ACTH (from a pituitary tumor or an ectopic source). ACTH-dependent Cushing syndrome due to a pituitary corticotroph adenoma is the most frequently diagnosed subtype, most commonly seen in women in the third through fifth decades of life. The onset is insidious and usually occurs 2 to 5 years before a clinical diagnosis is made.

 

Hypocortisolism most commonly presents with nonspecific lassitude, weakness, hypotension, and weight loss. Depending on the cause, hyperpigmentation may be present. More advanced cases and patients submitted to physical stress (ie, infection, spontaneous or surgical trauma) also may present with abdominal pain, hyponatremia, hyperkalemia, hypoglycemia, and in extreme cases, cardiovascular shock and renal failure.

 

The more common causes of hypocortisolism are:

Primary adrenal insufficiency:

-Addison disease

-Congenital adrenal hyperplasia, defects in enzymes involved in cortisol synthesis

 

Secondary adrenal insufficiency:

-Prior, prolonged corticosteroid therapy

-Pituitary insufficiency

-Hypothalamic insufficiency

 

See Steroid Pathways in Special Instructions.

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.

FREE CORTISOL

6-10:30 a.m. Collection: 0.121-1.065 mcg/dL

 

TOTAL CORTISOL

5-25 mcg/dL (a.m.)

2-14 mcg/dL (p.m.)

Pediatric reference ranges are the same as adults, as confirmed by peer-reviewed literature. 

 

Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scand 1981;70:341-345

Interpretation
Provides information to assist in interpretation of the test results

Cortisol is converted to cortisone in human kidneys and cortisone is less active toward the mineralocorticoid receptor. The conversion of cortisol to cortisone in the kidney is mediated by 11- beta-hydroxysteroid dehydrogenase isoform-2. Also, cortisol renal clearance will be reduced when there is a deficiency in the cytochrome P450 3A5 (CYP3A5) enzyme as well as a deficiency in P-glycoprotein.

 

Cortisol-binding globulin (CBG) has a low capacity and high affinity for cortisol, whereas albumin has a high capacity and low affinity for binding cortisol. Variations in CBG and serum albumin due to renal or liver disease may have a major impact on free cortisol.

 

Based on the study by Bancos(1), normal ranges of free cortisol found in patients without adrenal insufficiency were:

-Free cortisol at baseline: median 0.400 mcg/dL (interquartile range: IQR 2.5-97.5% - 0.110-1.425 mcg/dL)

-Free cortisol at 30 minutes: median 1.355 mcg/dL (IQR 2.5-97.5% - 0.885-2.440 mcg/dL)

-Free cortisol at 60 minutes: median 1.720 mcg/dL (IQR 2.5-97.5% - 1.230-2.930 mcg/dL)

 

Based on the study by Bancos,(1) the following cutoffs were calculated for exclusion of adrenal insufficiency:

-Free cortisol at baseline*: greater than 0.271 mcg/dL (>271 ng/dL, area under the curve: AUC 0.81)

-Free cortisol at 30 minutes: greater than 0.873 mcg/dL (>873 ng/dL, AUC 0.99)

-Free cortisol at 60 minutes: greater than 1.190 mcg/dL (>1,190 ng/dL, AUC 0.99)

(*please note that baseline free cortisol should not be used to exclude adrenal insufficiency given low performance)

 

The use of free cortisol in the management of glucocorticoid levels in the stressed patient due to major surgery or trauma requires further studies to establish clinical dosing levels and efficacy.

 

Cortisol pediatric reference ranges are generally the same as adults as confirmed by peer-reviewed literature.(2)

 

In primary adrenal insufficiency, adrenocorticotropic hormone (ACTH) levels are increased and cortisol levels are decreased; in secondary adrenal insufficiency both ACTH and cortisol levels are decreased.

 

When symptoms of glucocorticoid deficiency are present and the 8 a.m. plasma cortisol value is less than 10 mcg/dL (or the 24-hour urinary free cortisol value is <50 mcg/24 hours), further studies are needed to establish the diagnosis. The 3 most frequently used tests are the ACTH (cosyntropin) stimulation test, the metyrapone test, and insulin-induced hypoglycemia test. First, the basal plasma ACTH concentration should be measured and the short cosyntropin stimulation test performed.

 

Symptoms or signs of Cushing syndrome in a patient with low serum and urine cortisol levels suggest possible exogenous synthetic steroid effects.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Cortisol levels may be increased in pregnancy and with exogenous estrogens. Use of the antineoplastic drug Mitotane also increases cortisol-binding globulin and total cortisol.

 

When cortisol assays are used for serial monitoring, the same methodology should be used throughout.

 

There is little, if any, value in an isolated p.m. serum cortisol measurement.

 

Acute stress (including hospitalization and surgery), alcoholism, depression, and many drugs (ie, exogenous cortisones, anticonvulsants) can obliterate normal diurnal variation, affect response to suppression/stimulation tests, and cause elevated baseline levels.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Bancos I, Erickson D, Bryant S, et al: Performance of free versus total cortisol following cosyntropin stimulation testing in an outpatient setting. Endocr Pract. 2015 Dec;21(12):1353-1363 doi: 10.4158/EP15820

2. Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scand. 1981;70:341-345. doi: 10.1111/j.1651-2227.1981.tb16561.x. 

3. Hamrahian AH, Oseni TS, Arafah BM: Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350;16:1629-1638. doi: 10.1111/j.1651-2227.1981.tb16561.x.

4. Ho JT, Al-Musalhi H, Chapman MJ, et al: Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab. 2006;91:105-114. doi: 10.1210/jc.2005-0265. 

5. le Roux CW, Chapman GA, Kong WM, Dhillo WS, Jones J, Alaghband-Zadeh J: Free cortisol index is better than serum total cortisol in determining hypothalamic-pituitary-adrenal status in patients undergoing surgery. J Clin Endocrinol Metab. 2003;88:2045-2048. doi: 10.1210/jc.2002-021532.

6. Huang W, Kalhorn TF, Baillie M, Shen DD, Thummel KE: Determination of free and total cortisol in plasma and urine by liquid chromatography-tandem mass spectrometry. Ther Drug Monit. 2007;29(2):215-224. doi: 10.1097/FTD.0b013e31803d14c0. 

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Total Cortisol: 

Deuterated cortisol (d4-cortisol) is added to each specimen as an internal standard. Cortisol and d4-cortisol are extracted from the samples and analyzed by liquid chromatography-tandem mass spectrometry using multiple reaction monitoring. A calibration curve is included with each batch of patient samples.(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;1511-1519)

 

Free Cortisol:

Deuterated cortisol (d3-cortisol) is added as an internal standard and analyzed by liquid chromatography-tandem mass spectrometry.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

CINP: Monday through Friday

CORTF: Tuesday, Thursday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 7 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

See Individual Unit Codes

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82530

82533

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports