Cortisol

What is being tested?
Cortisol is a hormone produced by the adrenal glands. The production and release of cortisol is stimulated by ACTH (adrenocorticotrophic hormone), a hormone produced by the pituitary gland, a small organ located in the head below the brain. Cortisol has many functions: it acts on the metabolism of proteins, glucose and fats, keeps blood pressure stable and regulates the immune system. Heat, cold, infections, injuries, stress, exercise, obesity and debilitating illnesses can affect cortisol concentrations. The hormone is released in a daily cycle, rising in the early morning to a peak at about 8 am and falling in the evening. This cycle, sometimes called “diurnal variation” or “circadian rhythm”, changes if you work irregular shifts (for example night shifts) and sleep at different times of day.
Too little cortisol can cause non-specific symptoms such as weight loss, muscle weakness, tiredness, low blood pressure and abdominal pain. Sometimes reduced cortisol production combined with stress can cause an adrenal crisis, which needs immediate medical attention.

Too much cortisol can cause high blood pressure, high blood sugar, obesity, fragile skin, purple stretch marks on the abdomen, muscle weakness and osteoporosis. Women may have irregular periods and more facial hair, and children may have delayed development and short stature.

How is the sample collected for testing?
The blood sample is taken from a vein. Sometimes a urine or saliva sample is collected.

Blood cortisol should be measured at about 8 am, when the cortisol level should be at its highest, and again at about 4 pm, when the level should be falling. Sometimes a further sample may be taken late in the evening, when cortisol should be at its lowest concentration in the blood (at about midnight). Taking more than one sample allows the doctor to assess the daily pattern of cortisol secretion (the diurnal variation). This rhythm can be altered when too much cortisol is produced: the peak may be normal or close to normal, but the level may not fall as it should during the day. A single morning sample may be enough to detect a low cortisol concentration.
Cortisol can sometimes be measured in urine. This usually involves collecting all the urine passed over a day and a night (24-hour urine), but it can sometimes be done on a single morning urine sample. A 24-hour urine sample may be requested to measure free cortisol (not bound to proteins). This sample shows the total amount of free cortisol excreted in the urine, but does not allow doctors to assess changes in cortisol secretion

Cortisol can also be measured in saliva. Although collecting the sample is less stressful than a blood test, particular care is still needed to obtain it. The sample is often collected between 11 pm and midnight, when cortisol is normally at its lowest, to help diagnose Cushing’s syndrome

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
Blood and urine cortisol tests are used to help diagnose Cushing’s syndrome and Addison’s disease, two serious adrenal disorders. Some doctors use salivary cortisol to diagnose Cushing’s syndrome and to assess possible stress-related disorders, although this use is not widespread.

Saliva and urine tests are most often used to assess excess cortisol production.
If an abnormal cortisol concentration is found, the doctor will need to carry out further tests to confirm the excess or deficiency and find its cause.

Dexamethasone suppression
If too much cortisol is being produced, the doctor may carry out a dexamethasone suppression test to find out whether the cause is excess ACTH production by the pituitary gland. In this test the patient takes dexamethasone (a synthetic glucocorticoid) by mouth, and cortisol levels in the blood and urine are then measured. Dexamethasone suppresses ACTH production and should reduce cortisol production if the cause of the excess lies in the pituitary gland. There are several dosing schedules, but the medicine is usually given every 6 hours for 2 to 4 days before the blood or urine is collected. Separate 24-hour urine samples are collected before and throughout the test period, and the blood and urine samples are then analysed for cortisol and assessed.

ACTH stimulation
If the results of the first blood and/or urine tests indicate insufficient cortisol production, the doctor may order an ACTH stimulation test. This test measures the cortisol concentration in the patient’s blood before and after an injection of synthetic ACTH. If the adrenal glands are working normally, cortisol levels will rise with ACTH stimulation. If they are damaged, the response will be limited. A longer version of this test (1-3 days) may be carried out to distinguish between adrenal and pituitary insufficiency.

When is it requested?
A cortisol test may be requested when there are symptoms suggesting Cushing’s syndrome (obesity, muscle wasting and muscle weakness) or Addison’s disease (weakness, tiredness, increased pigmentation).
A suppression or stimulation test is done when the initial results are abnormal. Cortisol tests may be requested periodically when patients are being or have been treated for Cushing’s syndrome or Addison’s disease, to monitor the effectiveness of treatment.

What does the test result mean?
Normally cortisol levels are very low before going to bed and reach their highest levels just after waking. This rhythm changes if a person works irregular shifts (for example night shifts) and sleeps at different times of day. In Cushing’s syndrome this pattern is usually disrupted. Normal or high cortisol concentrations in the morning combined with a cortisol level that does not fall in the afternoon and evening suggest overproduction of cortisol. If this excess cortisol is suppressed during a dexamethasone suppression test, this indicates that it is due to increased pituitary ACTH production. If, on the other hand, it is not suppressed, the rise in cortisol may be due to a tumour producing ACTH outside the pituitary gland, a problem with the adrenal gland, or a medicine the patient is taking.

If the adrenal glands are very active, a patient may have Cushing’s syndrome, with signs and symptoms caused by prolonged exposure to the effects of high cortisol levels. This may be due to excess cortisol production by the adrenal glands (often because of a benign adrenal tumour) or to excess ACTH stimulation (due to a pituitary tumour or other ACTH-producing tumours). It can also be diagnosed in patients who need to take corticosteroid medicines, such as those used to treat asthma. If cortisol is insufficient and the patient responds to an ACTH stimulation test, the problem is probably due to insufficient ACTH production by the pituitary gland. If cortisol levels do not respond to ACTH stimulation tests, the problem is more likely to lie in the adrenal glands. If the adrenal glands are underactive, because of an adrenal problem or insufficient ACTH production, the patient is said to have adrenal insufficiency. If the low cortisol production is due to adrenal problems, the patient is said to have Addison’s disease.

Once the abnormality has been identified and linked to the pituitary gland, the adrenal glands or another cause, the doctor may use other investigations, such as CT (computed tomography) or MRI (magnetic resonance imaging) scans, to help locate the cause of the excess (such as pituitary, adrenal or other tumours) and assess the extent of any damage to the glands.

Is there anything else I should know?
Pregnancy, physical and emotional stress and illness can raise cortisol levels. They can also rise with hyperthyroidism and obesity. A number of medicines can also raise cortisol levels, particularly oral contraceptives (birth control pills), hydrocortisone (the synthetic form of cortisol) and spironolactone. Adults have slightly higher cortisol levels than children. Hypothyroidism can lower cortisol levels. Medicines that can lower cortisol include some steroid hormones.
The salivary cortisol test is used most often to help diagnose Cushing’s syndrome and stress-related disorders, but it must be carried out by specialised staff.

1. Do I need to have both tests (blood and urine), or is one more meaningful than the other?
2. How can I tell whether a high cortisol level is due to stress?

1. Do I need to have both tests (blood and urine), or is one more meaningful than the other?
If the doctor suspects Cushing’s syndrome, both the blood and the urine tests are usually carried out. The blood test is easier to do but is more affected by stress than the urine test. Salivary cortisol may sometimes be tested instead of blood cortisol.

2. How can I tell whether a high cortisol level is due to stress?
There are several approaches the doctor may consider. The simplest is to repeat the tests at a time when you feel less stressed. The doctor may also give you different doses of a medicine that replaces cortisol (usually dexamethasone) to see whether this lowers the cortisol level. Several investigations are often needed to find out whether stress or an illness is causing a high cortisol level.