Type of test
Blood; urine; saliva
Normal findings
Test explanation and related physiology
The best method of evaluating adrenal activity is by directly measuring plasma cortisol levels. Normally, cortisol levels rise and fall during the day; this is called the diurnal variation. Cortisol levels are highest around 6 am to 8 am and gradually fall during the day, reaching their lowest point around midnight. Sometimes the earliest sign of adrenal hyperfunction is only the loss of this diurnal variation, even though the cortisol levels are not yet elevated. For example, individuals with Cushing syndrome often have upper normal plasma cortisol levels in the morning and do not exhibit a decline as the day proceeds. High levels of cortisol indicate Cushing syndrome, and low levels of plasma cortisol are suggestive of Addison disease.
For this test, blood is usually collected at 8 am and again at around 4 pm. The 4 pm value is anticipated to be one-third to two-thirds of the 8 am value. Normal values may be transposed in individuals who have worked during the night and slept during the day for long periods of time.
The majority of cortisol circulates bound to corticosteroid binding globulin (CBG) and albumin. Normally, less than 5% of circulating cortisol is free (unbound). Total cortisol includes measurements of free and bound cortisol.
The measurement of late-night salivary cortisol is another effective test for Cushing syndrome. It seems to be more convenient and superior to plasma and urine for detecting cortisol in patients with mild Cushing syndrome. Salivary cortisol assay cannot be used to diagnose hypocortisolism or Addison disease because laboratory methods are not sensitive enough at low levels. If late-night salivary cortisol levels are elevated, the results should be confirmed with a repeat salivary cortisol measurement, a midnight blood sampling for cortisol, or a 24-hour urinary collection of free cortisol. A dexamethasone suppression test is another confirmation test that can be used.
Interfering factors
• Pregnancy is associated with increased levels.
• Physical and emotional stress can elevate cortisol levels.
• Variations in protein levels caused by renal or liver disease can affect free cortisol levels.
* Drugs that may cause increased levels include amphetamines, cortisone, estrogen, oral contraceptives, and spironolactone.
* Drugs that may cause decreased levels include androgens, aminoglutethimide, betamethasone and other exogenous steroid medications, danazol, lithium, levodopa, metyrapone, and phenytoin.
Procedure and patient care
Before
* Explain the procedure to the patient to minimize anxiety.
• Assess the patient for signs of physical stress (e.g., infection) and report these to the physician.
During
Blood
• Collect a venous blood sample in a red-top or green-top tube in the morning after the patient has had a good night’s sleep.
• Collect another blood sample at about 4 pm.
• Indicate the time of the venipuncture on the laboratory slip.
Saliva
1. Do not brush teeth before specimen collection.
2. Do not eat or drink for 15 minutes before specimen collection.
3. Collect the specimen between 11 pm and midnight and record the collection time.
4. Collect at least 1.5 mL of saliva in a Salivette as follows:
a. Place swab directly into mouth by tipping container so that swab falls into mouth. Do not touch swab with fingers.
b. Keep swab in mouth for approximately 2 minutes. Roll swab in mouth; do not chew swab.
c. Place swab back into its container without touching and replace the cap.
Urine
* Instruct the patient how to collect a 24-hour urine. See inside front cover for Routine Urine Testing.
• Keep the collection on ice and use a preservative.
After
• Apply pressure or a pressure dressing to the venipuncture site.
Abnormal findings
Increased levels
- Cushing syndrome
- Adrenal adenoma or carcinoma
- Ectopic ACTH-producing tumors
- Hyperthyroidism
- Obesity
- Stress
Decreased levels
- Congenital adrenal hyperplasia
- Addison disease
- Hypopituitarism
- Hypothyroidism
- Liver disease
