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, and is associated with too little cortisol. If cortisol concentrations are abnormal, additional testing may be required to confirm the diagnosis 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”).

Dexamethasone Suppression
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 level the following morning should be suppressed. This is the Overnight Dexamethasone Suppression Test and can be used to exclude Cushings 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 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 will rise following the injection. If they 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.

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 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 pill 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.

Adults have slightly higher cortisol levels than children. In normal people, cortisol levels are very low at bedtime, and at their highest just after waking. In Cushing's syndrome, this pattern is usually lost, so bedtime 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 gland. High blood and urine levels of cortisol indicate Cushing's syndrome. Low blood and urine levels, on the other hand are less useful for diagnosing Addison's disease, and a stimulation test, as indicated above, is often necessary.

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 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.

Hypothyroidism may decrease cortisol levels. Drugs that may decrease levels include some steroid hormones.