Blood, urine and saliva tests for cortisol are used to help diagnose Cushing’s syndrome and Addison’s disease, two serious disorders affecting the production of cortisol by the adrenal glands. Cushing's syndrome is caused by too much cortisol, while Addison’s disease is caused by damage to the adrenal, and is associated with too little cortisol. Drugs related to cortisol (e.g. prednisolone) will suppress cortisol secretion from the adrenal gland if taken for a period of time. 

If cortisol is abnormal, additional testing is usually required to confirm the diagnosis before you can receive appropriate treatment.

A cortisol test may be requested if your doctor notices symptoms suspicious of Cushing's syndrome (high blood pressure, obesity, muscle wasting and muscle weakness) or Addison's disease (low blood pressure, weakness, fatigue, increased pigment on the skin among others), and wishes to make a diagnosis. Because of the variety of factors which influence cortisol levels, a single measurement is not usually sufficient.

If Addison's disease is suspected it may be necessary to measure blood cortisol before and after a stimulus such as injection of Synacthen (a synthetic form of ACTH) to test the functioning of the adrenal glands.

If Cushing's syndrome is suspected, you may be asked to take a pill of dexamethasone (a drug that acts like cortisol and switches off ACTH secretion which is the normal stimulus for cortisol production) to make it easier to determine if you are making too much cortisol. Alternatively you may be given a tube to collect your saliva at midnight or asked to collect a 24 hour urine sample for cortisol measurement.

Adults have slightly higher morning cortisol levels than children. In healthy people, blood and saliva cortisol levels are very low at midnight, and at their highest just after waking.

In Cushing's syndrome this pattern, called the diurnal rhythm, is usually lost, so bedtime blood or saliva cortisol is often used when your doctor suspects this diagnosis.

Urine cortisol requires collecting all urine for a 24-hour period and provides information about total cortisol production by your adrenal glands over the whole day. High bed-time blood and saliva cortisol and high 24 hour urine cortisol results suggest Cushing's syndrome.

Low morning blood cortisol on the other hand is less accurate for diagnosing Addison's disease and a Synacthen stimulation test, as indicated above, is often necessary.

About Reference Intervals

Pregnancy, as well as physical and emotional stress, increases cortisol levels. Stress can increase your cortisol level and levels go up significantly when you are sick. Cortisol levels may also increase as a result of obesity. A number of drugs can also alter levels, particularly oral contraceptives (birth control pills), hydrocortisone (the synthetic form of cortisol) and prednisone and prednisolone.

People taking long-term oral steroid therapy are at risk of decreasing the ability of the adrenal glands to secrete cortisol normally.

If your doctor suspects Cushing's syndrome, both blood and urine may be tested. Blood cortisol is easier to collect but may be affected more by stress than the urine test. To diagnose Addison’s disease only blood cortisol is needed, but it is likely that samples before and after Synacthen injection will be needed.

There are several approaches that your doctor can take. The simplest involves repeating tests at a time when you feel less stressed. Your doctor can also give you varying doses of a medicine that replaces cortisol (usually a drug called dexamethasone) to see if this decreases your cortisol level. Multiple tests are often needed to tell if stress or disease is causing a high cortisol level.
 

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