Summary

• Although often known as the stress hormone, cortisol is needed for a range of important bodily processes.
• Cortisol levels are regulated by an area of the brain called the hypothalamus, together with the pituitary gland which sits at the base of your brain.
• Cortisol is made by the adrenal glands which sit on top of your kidneys.
• ACTH (adrenocorticotropic hormone) controls the level of cortisol in your body.
• Normally, ACTH rises when cortisol is low and falls when cortisol is high.
• If you make too much or too little cortisol, testing both cortisol and ACTH at the same time can help to show if you have a problem with your pituitary gland, adrenal glands or elsewhere in the body.

What is cortisol?

Cortisol is a steroid hormone that is involved in many different functions throughout the body. It is best known for priming your body to respond to stress – the fight or flight response. It also helps control your body’s use of fats, proteins and carbohydrates, reduces inflammation, regulates blood glucose levels and keeps blood pressure stable. It also plays a role in making sex hormones.

Cortisol levels follow a daily pattern, rising in the early morning, peaking at about 8 a.m., and falling in the evening. This is known as the diurnal rhythm. Infections, trauma, exercise, obesity and even being hot or cold influence the amount of cortisol made by your body and can disrupt this diurnal rhythm.

Your cortisol levels are controlled by a complex feedback system of hormones. Hormones are chemical messengers that are made by your glands. They travel in your bloodstream to control the actions of specific cells in your tissues or organs. When they reach their target, they attach to a cell’s receptors, stimulating a response.  

• Levels of cortisol are regulated by the hypothalamus, a cluster of cells located deep within your brain. Your hypothalamus is responsible for keeping your body’s nervous and endocrine systems in balance. Your endocrine system controls many of your body’s basic functions such as mood, growth and repair.
• The hypothalamus sends chemical messages to the pituitary, a small gland at the base of the brain.
• The pituitary then releases ACTH into your bloodstream.
• ACTH tells your adrenal glands to produce cortisol.
• The adrenals sit on top of each of your two kidneys.
• When levels of cortisol fall the hypothalamus sends signals to the pituitary to produce more ACTH and this tells the adrenal glands to produce cortisol, and when cortisol levels are too high the opposite happens.

Why get tested?

Cortisol and ACTH are usually requested to help diagnose Cushing's syndrome (including Cushing’s disease), tumours of the pituitary and adrenal glands, tumours in other parts of the body and Addison's disease. These are all rare conditions.

Cushing's syndrome

Cushing’s syndrome is caused when your body makes too much cortisol. It can cause many symptoms including weight gain and thinning skin. Your body can make too much cortisol for many reasons including:

• a tumour in the adrenal glands,  
• an overgrowth of the adrenal glands called adrenal nodule hyperplasia,
• a tumour somewhere else in the body that makes ACTH, or
• taking steroid medications for a long time, such as when you take steroids for an autoimmune disease.

When Cushing’s Syndrome is due to a tumour, the tumours are usually benign (not cancer).
 

Cushing's disease

Cushing’s disease is a type of Cushing’s syndrome. It is caused when there is a benign (non-cancerous) tumour in your pituitary gland which causes the pituitary gland to make too much ACTH. This extra ACTH stimulates your body to make more cortisol than it should. It is responsible for about eight out of 10 cases of Cushing’s syndrome.

Ectopic ACTH syndrome

Ectopic ACTH syndrome is when you have high ACTH levels because of a tumour elsewhere in your body, such as in the lungs, pancreas or thyroid. The most common type is small cell lung cancer. Ectopic ACTH syndrome is rare. 

Primary adrenal insufficiency - Addison's disease

In Addison's disease, which is called primary adrenal insufficiency, you have low levels of cortisol and high levels of ACTH. It is due to damage to the adrenal glands, and they do not produce as much cortisol as your body needs. This damage is often due to an autoimmune disease.

Secondary adrenal insufficiency

This is a condition in which the adrenal glands do not produce enough cortisol due to a problem with the pituitary gland or hypothalamus. As a result, your pituitary gland does not release enough ACTH to make your adrenal glands produce cortisol. This can be due to tumours, head trauma or long-term use of corticosteroids which can suppress ACTH production.

Congenital Adrenal Hyperplasia (CAH)

CAH is a group of inherited disorders that affect the production of cortisol in the adrenal glands. It is caused by mutations in genes responsible for producing enzymes (a type of protein) needed to make cortisol and cause an enzyme deficiency. The most common deficiency is for enzyme 21-hydroxylase. Children with CAH usually make too much male sex hormones and not enough cortisol and aldosterone. ACTH is measured in children suspected of having CAH.

Hypopituitarism

Hypopituitarism is a rare condition in which the pituitary gland does not make enough ACTH and cortisol. It is usually due to a benign tumour that affects the production of these hormones. As the tumour grows, it can press on and damage tissue in the pituitary. This disrupts the gland's ability to make hormones.

Having the test

Sample

Blood, urine and saliva.

Any preparation?

If your medical team wants to make sure that your high levels of cortisol are not just the result of your body being stressed, you may be asked to take a dexamethasone pill the night before having a cortisol test. Dexamethasone acts like cortisol and switches off ACTH production. It helps differentiate between Cushing’s syndrome and stress.

A low morning blood cortisol level does not necessarily mean you have Addison’s disease and a Synacthen stimulation test is often needed to make this diagnosis. Synacthen is a synthetic form of ACTH that stimulates the adrenal glands to produce cortisol.

Your results

Reading your test report

Your results will be presented along with those of your other tests on the same form. You will see separate columns or lines for each of these tests.

Factors influencing cortisol levels

• Pregnancy: Increases cortisol levels.
• Physical and Emotional Stress: Elevates cortisol levels, especially during illness.
• Obesity: Can lead to higher cortisol levels.
• Medications: Certain drugs, including oral contraceptives (birth control pills), hydrocortisone (prednisone and prednisolone) can alter cortisol levels.
• Long-term Oral Steroid Therapy: May reduce the adrenal glands' ability to make cortisol normally.

Cushing's syndrome

In healthy people, blood and saliva cortisol levels are very low at midnight and at their highest just after waking. Adults have slightly higher morning cortisol levels than children.

In Cushing's syndrome this pattern, called the diurnal rhythm, is usually lost, so late night blood or saliva 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 glands over the whole day. High late-night blood and saliva cortisol and high 24-hour urine cortisol results suggest Cushing's syndrome.

Questions to ask your doctor

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help. 

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely. 

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

More information

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.

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