To help diagnose Cushing syndrome or primary or secondary adrenal insufficiency (Addison disease); to detect conditions affecting the pituitary or adrenal glands
When your healthcare provider suspects excess or deficient cortisol production
A blood sample drawn from a vein in your arm or a random or 24-hour urine sample; sometimes a saliva sample may be used
You may be required to rest before sample collection. For a salivary cortisol test, you may be instructed to refrain from eating, drinking, or brushing your teeth for a period of time (may be some time between 15 to 30 minutes) prior to the test. Follow any instructions you are given.
Cortisol is a hormone that plays a role in the metabolism of proteins, lipids, and carbohydrates. It affects blood glucose levels, helps maintain blood pressure, and helps regulate the immune system. Most cortisol in the blood is bound to a protein; only a small percentage is "free" and biologically active. Free cortisol is secreted into the urine and is present in the saliva. This test measures the amount of cortisol in the blood, urine, or saliva.
The level of cortisol in the blood (as well as the urine and saliva) normally rises and falls in a "diurnal variation" pattern. It peaks early in the morning, then declines throughout the day, reaching its lowest level about midnight. This pattern can change when a person works irregular shifts (such as the night shift) and sleeps at different times of the day, and it can become disrupted when a disease or condition either limits or stimulates cortisol production.
Cortisol is produced and secreted by the adrenal glands, two triangular organs that sit on top of the kidneys. Production of the hormone is regulated by the hypothalamus in the brain and by the pituitary gland, a tiny organ located below the brain. When the blood cortisol level falls, the hypothalamus releases corticotropin-releasing hormone (CRH), which directs the pituitary gland to produce ACTH (adrenocorticotropic hormone). ACTH stimulates the adrenal glands to produce and release cortisol. In order for appropriate amounts of cortisol to be made, the hypothalamus, the pituitary, and the adrenal glands must be functioning properly.
The group of signs and symptoms that are seen with an abnormally high level of cortisol is called Cushing syndrome. Increased cortisol production may be seen with:
- Administration of large amounts of glucocorticosteroid hormones (such as prednisone, prednisolone, or dexamethasone) to treat a variety of conditions, such as autoimmune disease and some tumors
- ACTH-producing tumors, in the pituitary gland and/or in other parts of the body
- Increased cortisol production by the adrenal glands, due to a tumor or due to excessive growth of adrenal tissues (hyperplasia)
- Rarely, with tumors in various parts of the body that produce CRH
Decreased cortisol production may be seen with:
- An underactive pituitary gland or a pituitary gland tumor that inhibits ACTH production; this is known as secondary adrenal insufficiency.
- Underactive or damaged adrenal glands (adrenal insufficiency) that limit cortisol production; this is referred to as primary adrenal insufficiency and is also known as Addison disease.
- After stopping treatment with glucocorticosteroid hormones, especially if stopped very quickly after a long period of use
Typically, blood will be drawn from a vein in the arm, but sometimes urine or saliva may be tested. Cortisol blood tests may be drawn at about 8 am, when cortisol should be at its peak, and again at about 4 pm, when the level should have dropped significantly.
Sometimes a resting sample will be obtained to measure cortisol when it should be at its lowest level (just before sleep); this is often done by measuring cortisol in saliva rather than blood to make it easier to obtain the sample. Saliva for cortisol testing is usually collected by inserting a swab into the mouth and waiting a few minutes while the swab becomes saturated with saliva. Obtaining more than one sample allows the health practitioner to evaluate the daily pattern of cortisol secretion (the diurnal variation).
Sometimes urine is tested for cortisol; this usually requires collecting all of the urine produced during a day and night (a 24-hour urine) but sometimes may be done on a single sample of urine collected in the morning.
Some test preparation may be needed. Follow any instructions that are given as far as timing of sample collection, resting, and/or any other specific pre-test preparation.
A saliva test requires special care in obtaining the sample. You may be instructed to refrain from eating, drinking, or brushing your teeth for a period of time (may be some time between 15 to 30 minutes) prior to the test. Follow any specific instructions that are provided.
A stimulation or suppression test requires that you have a baseline blood sample drawn and then a specified amount of drug is given. Subsequent blood samples are drawn at specified times.
- How is it used?
A cortisol test may be used to help diagnose Cushing syndrome, a condition associated with excess cortisol, or to help diagnose adrenal insufficiency or Addison disease, conditions associated with deficient cortisol. Cortisol is a hormone that plays a role in the metabolism of proteins, lipids, and carbohydrates, among other functions. Normally, the level of cortisol in the blood rises and falls in a "diurnal variation" pattern, peaking early in the morning, then declining throughout the day and reaching its lowest level about midnight.
Cortisol is produced and secreted by the adrenal glands. Production of the hormone is regulated by the hypothalamus in the brain and by the pituitary gland, a tiny organ located below the brain. When the blood cortisol level falls, the hypothalamus releases corticotropin-releasing hormone (CRH), which directs the pituitary gland to produce ACTH (adrenocorticotropic hormone). ACTH stimulates the adrenal glands to produce and release cortisol. In order for appropriate amounts of cortisol to be made, the hypothalamus, the pituitary, and the adrenal glands must be functioning properly. (See the "What is being tested?" section for more.)
Most cortisol in the blood is bound to a protein; only a small percentage is "free" and biologically active. Blood cortisol testing evaluates both protein-bound and free cortisol while urine and saliva testing evaluate only free cortisol, which should correlate with the levels of free cortisol in the blood. Multiple blood and/or saliva cortisol levels collected at different times, such as at 8 am and 4 pm, can be used to evaluate both cortisol levels and diurnal variation. A 24-hour urine cortisol sample will not show diurnal variation; it will measure the total amount of unbound cortisol excreted in 24 hours.
If an abnormal level of cortisol is detected, a health practitioner will do additional testing to help confirm the findings and to help determine its cause:
Testing for Excess Cortisol Production
If a person has a high blood cortisol level, a health practitioner may perform additional testing to confirm that the high cortisol is truly abnormal (and not simply due to increased stress or the use of cortisol-like medication). This additional testing may include measuring the 24-hour urinary cortisol, doing an overnight dexamethasone suppression test, and/or collecting a salivary sample before retiring in order to measure cortisol at the time that it should be the lowest. Urinary cortisol requires the collection of urine over a timed period, usually 24 hours. Since ACTH is secreted by the pituitary gland in pulses, this test helps determine whether the elevated blood cortisol level represents a real increase.
Dexamethasone suppression: The dexamethasone suppression test involves analyzing a baseline sample for cortisol, then giving the person oral dexamethasone (a synthetic glucocorticoid) and measuring cortisol levels in subsequent timed samples. Dexamethasone suppresses ACTH production and should decrease cortisol production if the source of the excess is stress.
Collecting a salivary sample for cortisol measurement is a convenient way to determine whether the normal rhythm of cortisol production is altered. If one or more of these tests confirms that there is abnormal cortisol production, then additional testing, including measuring ACTH, repeating the dexamethasone suppression test using higher doses, and radiologic imaging may be ordered.
Testing for Insufficient Cortisol Production
If a health practitioner suspects that the adrenal glands may not be producing adequate cortisol or if the initial blood tests indicate insufficient cortisol production, the health practitioner may order an ACTH stimulation test.
ACTH stimulation: This test involves measuring the level of cortisol in a person's blood before and after an injection of synthetic ACTH. If the adrenal glands are functioning normally, then cortisol levels will rise with the ACTH stimulation. If they are damaged or not functioning properly, then the cortisol level will be low. A longer version of this test (1-3 days) may be performed to help distinguish between adrenal and pituitary insufficiency.
- When is it ordered?
A cortisol test may be ordered when a person has symptoms that suggest a high level of cortisol and Cushing syndrome, such as
- High blood pressure (hypertension)
- High blood sugar (glucose)
- Obesity, especially in the trunk
- Fragile skin
- Purple streaks on the abdomen
- Muscle wasting and weakness
Testing may be ordered when women have irregular menstrual periods and increased facial hair; children may have delayed development and a short stature.
This test may be ordered when someone has symptoms suggestive of a low level of cortisol, adrenal insufficiency, or Addison disease, such as:
- Weight loss
- Muscle weakness
- Low blood pressure
- Abdominal pain
- Dark patches of skin (this occurs in Addison disease but not secondary adrenal insufficiency)
Sometimes decreased production combined with a stressor can cause an adrenal crisis that can be life-threatening and requires immediate medical attention. Symptoms of a crisis may include:
- Sudden onset of severe pain in the lower back, abdomen, or legs
- Vomiting and diarrhea, resulting in dehydration
- Low blood pressure (hypotension)
- Loss of consciousness
Suppression or stimulation testing is ordered when initial findings are abnormal. Cortisol testing may be ordered at intervals after a diagnosis of Cushing syndrome or Addison disease to monitor the effectiveness of treatment.
- What does the test result mean?
Normally, cortisol levels are very low at bedtime and at their highest just after waking, though this pattern will change if a person works rotating shifts and sleeps at different times on different days.
An increased or normal cortisol level just after waking along with a level that does not drop by bedtime suggests excess cortisol and Cushing syndrome. If this excess cortisol is not suppressed after an overnight dexamethasone suppression test, or if the 24-hour urine cortisol is elevated, or if the late-night salivary cortisol level is elevated, it suggests that the excess cortisol is due to abnormal increased ACTH production by the pituitary or a tumor outside of the pituitary or abnormal production by the adrenal glands. Additional testing will help to determine the exact cause. (See the section "How is it used?" above.)
If insufficient cortisol is present and the person tested responds to an ACTH stimulation test, then the problem is likely due to insufficient ACTH production by the pituitary. If the person does not respond to the ACTH stimulation test, then it is more likely that the problem is based in the adrenal glands. If the adrenal glands are underactive, due to pituitary dysfunction and/or insufficient ACTH production, then the person is said to have secondary adrenal insufficiency. If decreased cortisol production is due to adrenal damage, then the person is said to have primary adrenal insufficiency or Addison disease.
Once an abnormality has been identified and associated with the pituitary gland, adrenal glands, or other cause, then the health practitioner may use other testing such as CT (computerized tomography) or MRI (magnetic resonance imaging) scans to locate the source of the excess (such as a pituitary, adrenal, or other tumor) and to evaluate the extent of any damage to the glands.
- Is there anything else I should know?
Similar to those with adrenal insufficiency, people with a condition called congenital adrenal hyperplasia (CAH) have low cortisol levels and do not respond to ACTH stimulation tests. Cortisol measurement is one of many tests that may be used to help evaluate a person for CAH.
Heat, cold, infection, trauma, exercise, obesity, and debilitating disease can influence cortisol concentrations. Pregnancy, physical and emotional stress, and illness can increase cortisol levels. Cortisol levels may also increase as a result of hyperthyroidism or obesity. A number of drugs can also increase levels, particularly oral contraceptives (birth control pills), hydrocortisone (the synthetic form of cortisol), and spironolactone.
Adults have slightly higher cortisol levels than children do.
Hypothyroidism may decrease cortisol levels. Drugs that may decrease levels include some steroid hormones.
Salivary cortisol testing is being used more frequently to help diagnose Cushing syndrome and stress-related disorders but still requires specialized expertise to perform.
- Do I need both tests (blood and urine) or is one better than the other?
If your healthcare provider suspects Cushing syndrome, usually both blood and urine are tested as they offer complementary information. Blood cortisol is easier to collect but is affected more by stress than is the 24-hour urine test. Salivary cortisol may sometimes be tested instead of blood cortisol.
- How do I tell if a high cortisol level isn't just from stress?
There are several approaches that your healthcare provider can take. The simplest involves repeating tests at a time when you feel less stressed. Your healthcare provider can also give you varying doses of a medicine that replaces cortisol (usually 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.