If your doctor suspects an underactive, or damaged adrenal gland with too little production of cortisol, or a condition that could result in the body producing too much cortisol. Ensure your healthcare professional is aware if you are currently or recently have been taking steroid medication (such as hydrocortisone, prednisone, prednisolone, dexamethasone), as these can affect test results.
Typically, a blood sample will be taken by a syringe with needle 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 near their nocturnal 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 still be at or near normal concentrations, but concentrations 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 (urinary free 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 the pattern of 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. Your doctor may have different methods for saliva collection. Please follow any instructions that you are given.
Some preparation for the test may be needed. Follow any instructions that are given as far as timing of the 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 taken and are then given a specified amount of a drug. Subsequent blood samples are drawn at specific times. Please follow any instructions that you are given.
Cortisol is a steroid hormone, produced by the adrenal gland, which is essential for survival. Cortisol is a steroid hormone that breaks down fat and protein and stimulates glucose production in the liver. It helps the body react to physical and emotional stress, helps to regulate blood pressure, to control inflammation, and can affect cardiovascular function. The production and secretion of cortisol is stimulated by adrenocorticotrophic hormone (ACTH) 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 (circadian rhythm), rising in the early morning, through several pulses peaking around 8 a.m.(nocturnal pattern), and declining in the day to lowest concentrations in the evening (diurnal rhythm). The 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 as a result of:
- An underactive pituitary gland or a pituitary gland tumour that prevents 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.
Too much cortisol within the bloodstream can cause increased blood pressure, high blood sugar (glucose) concentrations, obesity, fragile skin, purple streaks on the tummy and muscle weakness. 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 as a result of:
How is it used?
Blood and urine tests for cortisol are used to help diagnose two disorders affecting the production of cortisol by the adrenal gland. Cushing syndrome is caused by too much cortisol, while Addison 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 production of cortisol, 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 syndrome if there is a low clinical 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. Causes include:
- excess ACTH production by an adenoma of the pituitary (Cushing disease)
- abnormal cortisol production by an adenoma (tumour) of the adrenals (cushings syndrome)
- production of ACTH by a tumour in the body other than the pituitary (ectopic production).
ACTH (“Synacthen”) Stimulation
If the findings of the initial blood test and/or the clinical symptoms suggest insufficient cortisol production, a synacthen stimulation test may be performed. This test involves measuring the concentration of cortisol before and usually 30 minutes and/or 1 hour after an injection of synacthen (depending on the local practice). 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 observes symptoms suspicious of Cushing syndrome (high blood pressure, obesity, muscle wasting, and muscle weakness) or Addison disease (low blood pressure, weakness, fatigue, increased pigment on the skin among others). Because of the variety of factors which influence cortisol concentration within the blood, a single measurement is not usually sufficient. If Addison 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 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. Normally, cortisol concentrations in the blood are very low at bedtime, and at their highest just after waking. In Cushing syndrome, this diurnal 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 syndrome. Low blood and urine concentrations, on the other hand are less useful for diagnosing Addison 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
ACB, Analyte Monographs (AMALC): Cortisol Urine
ACB, Analyte Monographs (AMALC): Cortisol
NHS: Cushing Syndrome
NHS: Addison Disease
Pituary.org: Cushing Disease
Addison Disease Self Help Group