NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Screening for Cushing syndrome
Diagnosis of Cushing syndrome in patients presenting with symptoms or signs suggestive of the disease
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Nighttime Salivary Cortisol
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: SARSTEDT Salivette (Supply T514)
Specimen Volume: 1.5 mL
1. Do not brush teeth before collecting specimen.
2. Do not eat or drink for 15 minutes prior to specimen collection.
3. Collect specimen between 11 p.m. and midnight, and record collection time.
4. To use the Salivette:
a. Remove top cap of container to expose swab.
b. Place swab directly into mouth by tipping container so swab falls into mouth. Do not touch swab with fingers.
c. Keep swab in mouth for approximately 2 minutes. Roll swab in mouth, do not chew swab.
d. Place swab back into its container without touching, and replace the cap.
e. Record collection time, and send appropriately labeled Salivette to laboratory.
1. Reference values are also available for 8 a.m. (7 a.m.-9 a.m.) and 4 p.m. (3 p.m.-5 p.m.) collections, however, 11 p.m. to midnight collection is preferred.
2. Indicate collection time.
3. If multiple specimens are collected, submit each vial under a separate order.
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Saliva||Refrigerated (preferred)||7 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Cortisol levels are regulated by adrenocorticotropic hormone (ACTH), which is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH). Cushing syndrome results from overproduction of glucocorticoids as a result of 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.
CRH is released in a cyclic fashion by the hypothalamus, resulting in diurnal peaks (elevated in the morning) and nadirs (low in the evening) for plasma ACTH and cortisol levels. The diurnal variation is lost in patients with Cushing and these patients have elevated levels of evening plasma cortisol. The measurement of late-night salivary cortisol is an effective and convenient screening test for Cushing syndrome.(1) In a recent study from the National Institute of Health, nighttime salivary cortisol measurement was superior to plasma and urine free cortisol assessments in detecting patients with mild Cushing syndrome.(2) The sensitivity of nighttime salivary cortisol measurements remained superior to all other measures. The distinction between Cushing syndrome and pseudo-Cushing states is most difficult in the setting of mild to moderate hypercortisolism. Subtle increases in salivary cortisol at the midnight cortisol (cortisol of nadir) appear to be 1 of the earliest abnormalities in Cushing syndrome.
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.
7 a.m.-9 a.m.: 100-750 ng/dL
3 p.m.-5 p.m.: <401 ng/dL
11 p.m.-midnight: <100 ng/dL
Cushing syndrome is characterized by increased salivary cortisol levels, and late-night saliva cortisol measurements may be the optimum test for the diagnosis of Cushing. It is standard practice to confirm elevated results at least once. This can be done by repeat late-night salivary cortisol measurements, midnight blood sampling for cortisol (CORT Cortisol, Serum), 24-hour urinary free cortisol collection (CORTU/8546 Cortisol, Urine), or overnight dexamethasone suppression testing. Upon confirmation of the diagnosis, the cause of hypercortisolism, adrenal versus pituitary versus ectopic adrenocorticotropic hormone production, needs to be established. This is typically a complex undertaking, requiring dynamic testing of the pituitary adrenal axis and imaging procedures. Referral to specialized centers or in-depth consultation with experts is strongly recommended.
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 glucocorticoids, anticonvulsants) can obliterate normal diurnal variation, affect response to suppression/stimulation tests, and cause elevated cortisol levels.
Cortisol levels may be increased in pregnancy and with exogenous estrogens.
Midnight salivary cortisol assay cannot diagnose hypocortisolism or Addison disease because of the limited sensitivity of the assay method.
Using this assay we determined that late night salivary cortisol is in the range of 100 ng/mL to 6,000 ng/dL (2.76-166 nmol/L) for clinically confirmed Cushing patients (N=11).
Normal values are based on 36 donors-ages 0 to 8 years, 46 donors-ages 9 to 17 years, and 102 donors->17 years.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Raff H, Raff JL, Findling JW: Late-night salivary cortisol as a screening test for Cushing's syndrome. J Clin Endocrinol Metab 1998;83:2681-2686
2. Papanicolaou DA, Mullen N, Kyrou I, Nieman LK: Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 2002;87:4515-4521
Method Description Describes how the test is performed and provides a method-specific reference
Deuterated cortisol (d3-cortisol) is added to 0.1 mL sample as an internal standard. Cortisol and d3-cortisol are extracted from the specimen using on-line turbulent flow HPLC and analyzed by liquid chromatography-tandem mass spectrometry using multiple reaction monitoring in positive mode. The following transitions are used for analysis: Cortisol: 363.3/121.1; d3-cortisol: 366.3/121.1.(Taylor RL, Machacek DA, Singh RJ: Validation of a high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and cortisone. Clin Chem 2002; 48:1511-1519)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Wednesday, Friday; 1 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|