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)
Nighttime Salivary Cortisol
Salivary Cortisol
Salivary Cushings
Salivary Hydrocortisone
Saliva
Collection time is required.
Question ID | Description | Answers |
---|---|---|
COLT3 | Collection Time in Military Time |
Patient Preparation:
1. Do not brush teeth before collecting specimen.
2. Do not eat or drink for 15 minutes prior to specimen collection.
Supplies: Cortisol, Saliva Collection Kit (T514)
Container/Tube: SARSTEDT Salivette
Specimen Volume: 1.5 mL
Collection Instructions:
1. Provide patient with a Saliva Collection Kit (Salivette) containing the Cortisol - Saliva Collection Instructions and ask them to follow the instructions as written.
2. Instruct patient to collect specimen between 11 p.m. and midnight and record collection time on the Cortisol - Saliva Collection Instructions sheet.
3. Instruct patient to return Cortisol - Saliva Collection Instructions with the appropriately labeled Salivette to the laboratory.
Additional Information:
1. Reference values are also available for an 8 a.m. (7 a.m.-9 a.m.) or a 4 p.m. (3 p.m.-5 p.m.) collection, however, the 11 p.m. to midnight collection is preferred.
2. If multiple specimens are collected, submit each vial under a separate order.
If not ordering electronically, complete, print, and send General Request (T239)
0.6 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Saliva | Refrigerated (preferred) | 28 days | |
Frozen | 60 days | ||
Ambient | 28 days |
Screening for Cushing syndrome
Diagnosis of Cushing syndrome in patients presenting with symptoms or signs suggestive of the disease
Cortisol levels are regulated by corticotropin (previously adrenocorticotropic hormone: ACTH), which is synthesized by the pituitary in response to corticotropin-releasing hormone (CRH). Cushing syndrome results from overproduction of glucocorticoids because 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; commonly seen in women in the third through fifth decades of life.
Corticotropin-releasing hormone is released in a cyclic fashion by the hypothalamus, resulting in diurnal peaks (elevated in the morning) and troughs (low in the evening) for plasma ACTH and cortisol levels. The diurnal variation is lost in patients with Cushing syndrome 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 collected at midnight (cortisol of nadir) appear to be one of the earliest abnormalities in Cushing syndrome.
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
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, it was determined that late-night salivary cortisol is in the range of 100 ng/mL to 6000 ng/dL (2.76-166 nmol/L) for clinically confirmed Cushing patients (N=11).
Normal values are based on 36 donors (ages 0-8 years), 46 donors (ages 9-17 years), and 102 donors (age >17 years).
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
3. 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;82:151-155
4. Mohamed RS, Abuelgasim B, Barker S, et al. Late-night salivary cortisol and cortisone should be the initial screening test for Cushing's syndrome. Endocr Connect. 2022;11(7):e220050. doi:10.1530/EC-22-0050
Isotopically labeled cortisol and cortisone are added to the sample as internal standards. Cortisol, cortisone, and coinciding internal standards are extracted from the specimens using online turbulent flow chromatography, which is followed by liquid chromatography tandem mass spectrometry analysis. Although cortisone is not reported, it is used to verify the cortisol value and screen for possible contamination from exogenous sources.(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.
82533
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
SALCT | Cortisol, Saliva | 2142-8 |
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.
|
---|---|---|
84225 | Cortisol, Saliva | 2142-8 |
23612 | AM Cortisol | 58674-3 |
23613 | PM Cortisol | 58668-5 |
23614 | Midnight Cortisol | 58642-0 |