Cortisol

Both the urine and saliva tests are most frequently used to evaluate excess cortisol production.

Once an abnormal cortisol concentration has been detected, the doctor will do additional testing to help confirm the excess or deficiency and to help determine its cause.

Dexamethasone Suppression
If there is excess cortisol production, the doctor may perform a dexamethasone suppression test to help determine whether the cause of the cortisol is related to excess ACTH production by the pituitary. This test involves giving the patient oral dexamethasone (a synthetic glucocorticoid) and then measuring their blood and urine cortisol levels. Dexamethasone suppresses ACTH production and should decrease cortisol production if the source of the excess is pituitary related. There are a variety of dosing schedules, but the medication is usually given every 6 hours for either 2 or 4 days prior to blood or urine collection. Separate 24-hour urine samples are collected prior to and throughout the testing period and then the blood and urine samples are measured for cortisol and evaluated.

ACTH Stimulation
If the findings of the initial blood and/or urine tests indicate insufficient cortisol production, the doctor may order an ACTH stimulation test. This test involves measuring the concentration of cortisol in a patient’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, then the response will be limited. A longer version of this test (1-3 days) may be performed to help distinguish between adrenal and pituitary insufficiency.

Suppression or stimulation testing is ordered when initial findings are abnormal. Cortisol testing may be ordered at intervals when patients are being or have been treated for Cushing’s syndrome or Addison’s disease to monitor the effectiveness of treatment.

Increased or normal cortisol concentrations in the morning along with levels that do not drop in the afternoon and evening suggest an overproduction of cortisol. If this excess cortisol is suppressed during a dexamethasone suppression test, it suggests that the excess cortisol is due to increased pituitary ACTH production. If it is not suppressed, then the increased cortisol could be due to an ACTH-producing tumor outside of the pituitary, due to a problem with the adrenal gland, or due to a medication that the patient is taking.

If the adrenal glands are overactive, then a patient may have Cushing’s syndrome, with symptoms and signs caused by prolonged exposure to the effects of too much cortisol. This may be due to excess production of cortisol by the adrenal glands (which is frequently due to a benign adrenal tumor) or excess ACTH stimulation (due to a pituitary or other ACTH-producing tumor). It can also be seen in patients who must take corticosteroid medications, such as those used to treat asthma. If insufficient cortisol is present and the patient responds to an ACTH stimulation test, then the problem is likely due to insufficient ACTH production by the pituitary. If cortisol levels do 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 adrenal damage or insufficient ACTH production, then the patient is said to have adrenal insufficiency. If decreased cortisol production is due to adrenal damage, then the patient is said to have Addison’s disease.

Once an abnormality has been identified and associated with the pituitary gland, adrenal glands, or other cause, then the doctor 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.

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's syndrome and stress-related disorders but still requires specialized expertise to perform.