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 (often between 15 to 30 minutes) prior to the test. Please discuss the instructions given by your local laboratory with your doctor and ensure you follow any instructions given.
Cortisol is a steroid hormone, produced by the adrenal gland, which is essential for survival. Production and secretion of cortisol is stimulated by ACTH (adrenocorticotropic hormone), a hormone produced by the pituitary gland – a tiny organ located inside the head below the brain. The concentration of cortisol in the blood increases during times of stress, and it also helps regulate the immune system. Heat, cold, infection, trauma, exercise, obesity, and debilitating disease influence cortisol secretion. The hormone is secreted in a daily pattern, rising in the early morning, peaking around 8 a.m., and declining in the evening. This pattern, a “diurnal variation” or “circadian rhythm,” can change in long term night shift workers.
Inadequate concentrations of cortisol within the blood can cause nonspecific symptoms such as weight loss, muscle weakness, fatigue, low blood pressure or abdominal pain and exposure to stress can cause an adrenal crisis that requires immediate medical attention.
Decreased cortisol production may be seen with:
Too much cortisol within the bloodstream can cause increased blood pressure, high blood sugar (glucose) concentrations, obesity, fragile skin, purple streaks on the tummy, muscle weakness, and osteoporosis. Women may have irregular menstrual periods and increased hair on the face; children may have delayed development and a short stature.
Increased cortisol production may be seen with:
How is the sample collected for testing?
Typically, blood will be taken from a vein in the arm, but sometimes urine or saliva may be tested. Blood should ideally be collected between 8-9am when blood cortisol concentrations should be at their peak. A second sample may be taken late in the evening when cortisol should be at its lowest concentration (about midnight). Samples collected at these times allow the doctor to evaluate the daily pattern of cortisol secretion (the diurnal variation). This pattern may be disrupted with excess cortisol production – the maximum amount may be at or near normal concentrations, but levels may not fall as they should throughout the day. A single morning sample may be sufficient to detect decreased concentrations of cortisol.
Sometimes urine is tested for cortisol; this requires collecting all urine produced during a day (24-hour urine). This sample will reflect the total amount of cortisol produced in the 24 hour period but will not allow doctors to evaluate variations in cortisol secretion.
If a saliva sample is required for testing, the sample will be collected by inserting a swab into the mouth and waiting a few minutes while the swab becomes saturated with saliva.
Is any test preparation needed to ensure the quality of the sample?
Some test preparation may be needed. Follow any doctor’s 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 (often between 15 to 30 minutes) prior to the test. Please discuss the instructions given by your local laboratory with your doctor and ensure you follow any instructions given.
A stimulation or suppression test requires that you have a baseline blood sample drawn and are then given a specified amount of drug. Subsequent blood samples are drawn at specific times.
How is it used?
Blood and urine 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 gland. Cushing's syndrome is caused by too much cortisol, while Addison's disease is caused by damage to the adrenal gland, and is associated with too little cortisol. If cortisol concentrations are abnormal, additional testing may be required to confirm the diagnosis and decide on treatment. These further tests may involve a test to suppress cortisol production with dexamethasone or a test to stimulate the adrenal gland to produce cortisol, using a synthetic form of ACTH (“Synacthen”).
If there is apparent excess cortisol production, a dexamethasone suppression test can be used to help determine the cause. Dexamethasone is a synthetic steroid with many actions similar to cortisol. When taken orally, dexamethasone suppresses ACTH production by the pituitary gland and hence cortisol production by the adrenals. There are different forms of the test. In its simplest form, a single tablet is taken at midnight and cortisol is measured the following morning – in normal individuals the cortisol concentration the following morning should be suppressed. This is known as the overnight dexamethasone suppression test and can be used to exclude Cushing’s syndrome if there is a low index of suspicion. A longer form of the test may involve the patient coming to hospital, taking increasing doses of the medication over several days with multiple blood and urine measurements. This is used to help determine the cause of excess cortisol production such as excess ACTH production by an adenoma of the pituitary, autonomous cortisol production by an adenoma of the adrenals or due to production of ACTH by a tumour elsewhere in the body (ectopic production).
ACTH (“Synacthen”) Stimulation
If the findings of the initial blood test and/or the patients symptoms suggest insufficient cortisol production, a synacthen stimulation test may be performed. This test involves measuring the concentration of cortisol in a patient’s blood before and after an injection of synacthen. If the adrenal glands are functioning normally, then cortisol levels within the blood will rise following the injection. If the adrenal glands are damaged, then the response will be limited. Occasionally, a longer version of the test (1-3 days) may be performed to help distinguish between adrenal and pituitary insufficiency.
When is it requested?
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 concentration within the blood, a single measurement is not usually sufficient. If Addison's disease is suspected it may be necessary to measure the response of the adrenal glands to a stimulus such as injection of synacthen (a synthetic form of ACTH, the hormone that stimulates the adrenal glands to produce cortisol). Alternatively if Cushing's syndrome is suspected, you may be asked to take a tablet of dexamethasone (a drug that acts like cortisol and switches off the normal stimulus for cortisol production) to make it easier to determine if you are making too much cortisol.
What does the test result mean?
Adults have slightly higher cortisol concentrations than children. In normal people, cortisol concentrations in the blood are very low at bedtime, and at their highest just after waking. In Cushing's syndrome, this pattern is usually lost, so bedtime cortisol measurement is often used when your doctor suspects this diagnosis.
Measurement of urine cortisol requires collecting all urine for a 24-hour period, and provides information about the total cortisol production by your adrenal gland. High blood and urine concentrations of cortisol suggest Cushing's syndrome. Low blood and urine concentrations, on the other hand are less useful for diagnosing Addison's disease, and a stimulation test, as indicated above, is often necessary.
Is there anything else I should know?
Pregnancy, as well as physical and emotional stress, increases cortisol concentrations within the bloodstream. Stress can increase cortisol and levels go up significantly when you are sick. Cortisol concentrations in the blood may also increase as a result of hyperthyroidism or obesity. A number of drugs can also increase cortisol, particularly oral contraceptives (birth control pills), hydrocortisone (the synthetic form of cortisol), and spironolactone.
Hypothyroidism may decrease the concentration of cortisol in the blood. Drugs that may decrease levels include some steroid hormones.
Do I need both tests (blood and urine), or is one better than the other?
How do I tell if a high cortisol level isn't just from stress?
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 use a dexamethasone suppression test 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.
Elsewhere On The Web
Analyte Monographs alongside the National Laboratory Medicine Catalogue (AMALC): Cortisol Urine
Analyte Monographs alongside the National Laboratory Medicine Catalogue (AMALC): Cortisol
NHS Choices: Cushing's Syndrome
NHS Choices: Addison's Disease
Pituary.org: Cushing's Disease
Addison's Disease Self Help Group