Summary

• The short synacthen test is used to see whether your adrenal glands are producing enough cortisol.
• It is mainly used when adrenal insufficiency, including Addison’s disease, is suspected.
• Synacthen is a manufactured form of the hormone ACTH.
• ACTH is normally produced by the pituitary gland and stimulates the adrenal glands to make cortisol.
• The test involves having an injection of synacthen and then measuring the rise in cortisol in your blood to see how well your adrenal glands respond.
• A low or inadequate rise in cortisol may suggest that your adrenal glands are not producing enough cortisol.
   

How your adrenal glands make cortisol

Hormones are your body’s chemical messages that are sent out from various glands to affect the way your body works.

• The hypothalamus, a cluster of cells located deep within your brain, is responsible for keeping your body’s nervous and hormone systems in balance.
• The hypothalamus sends chemical messages to the pituitary, a small gland at the base of the brain to make ACTH (a hormone). The hypothalamus is connected to the pituitary gland by a stalk of blood vessels and nerves.
• The pituitary releases ACTH into your bloodstream. This travels to your adrenal glands that sit on top of each of your two kidneys where it stimulates them to make cortisol.
• For the right amount of cortisol to be made, the hypothalamus, the pituitary and the adrenal glands must all be working together.

For more on this see cortisol, ACTH and aldosterone and renin.
 

What is the short synacthen test?

The short synacthen test is used to see whether your adrenal glands can produce enough cortisol. It is mainly used when adrenal insufficiency, including Addison’s disease, is suspected.

Synacthen is a manufactured form of ACTH (adrenocorticotropic hormone). It acts like ACTH, stimulating the adrenal glands to produce cortisol. By measuring how much cortisol rises after synacthen is given, the test can show how well your adrenal glands are working.

What happens in the test?

• A blood sample is first taken to measure your baseline cortisol level.
• Next, you are given an injection of synacthen. Further blood samples are taken to measure the rise in cortisol, usually at 30 minutes and again at 60 minutes.
• A low rise in cortisol or no rise in cortisol suggests that your adrenal glands are not producing enough cortisol.

Why get tested?

Adrenal insufficiency
The short synacthen test is mostly used to investigate adrenal insufficiency. There are two forms:

• Primary adrenal insufficiency – Addison’s disease
  In Addison's disease, you have high levels of ACTH and low levels of cortisol. It is due to damage to the adrenal glands so they cannot make the amount of cortisol needed by the body. This is often due to an autoimmune disease. It can also be caused by a severe infection like tuberculosis, HIV, fungal diseases or cancer spreading to the adrenal glands from somewhere else in the body.
• Secondary adrenal insufficiency
  In secondary adrenal insufficiency, the pituitary gland does not produce enough ACTH so the level is low, and cortisol levels are also low. Your pituitary gland doesn’t release enough ACTH to make your adrenal glands produce cortisol. This can be caused by several conditions including long-term steroid use (which suppresses the adrenal glands), suddenly stopping medicines like prednisone after a long time of use, pituitary tumours (which are usually non-cancerous), brain damage near the hypothalamus or reduced blood flow such as from strokes or severe blood loss.

A typical investigation for suspected adrenal insufficiency

1. Cortisol is usually the first test performed. A clearly normal result may make adrenal insufficiency unlikely, while a low or borderline result may need further investigation.
2. ACTH is usually measured at the same time as the initial cortisol, particularly if adrenal insufficiency is suspected. It helps show whether the problem is in the adrenal glands or higher up in the pituitary or hypothalamus.
3. Short synacthen test is performed when the initial cortisol result does not clearly confirm or exclude adrenal insufficiency.
4. Aldosterone is another hormone produced by the adrenal glands is often tested. Aldosterone helps control blood pressure and fluid balance by regulating how much sodium and potassium the kidneys retain or remove. Unlike cortisol, aldosterone is not mainly controlled by ACTH. It is regulated primarily by the kidneys together with another hormone called renin.  
   
   Measuring aldosterone and renin can help distinguish between primary and secondary adrenal insufficiency. In primary adrenal insufficiency, where the adrenal glands themselves are damaged, aldosterone is usually low and renin is high (because the kidneys are trying to compensate for the low aldosterone.) In secondary adrenal insufficiency, where the adrenals are still working aldosterone production is usually maintained, so aldosterone and renin are generally normal while reduced ACTH from the pituitary causes low cortisol production.

For more see cortisol, ACTH and aldosterone and renin.

Congenital adrenal hyperplasia (CAH)
The short synacthen test is also sometimes used to diagnose congenital adrenal hyperplasia (CAH) and non-classical 21-hydroxylase deficiency. These are a group of inherited conditions that affect the adrenal glands' ability to make steroid hormones. Another adrenal gland hormone, 17-hydroxyprogesterone, is usually measured at the same time.
 

Any more to know?

Synacthen is called short because it is a synthetic version of part of the natural ACTH hormone. Natural ACTH contains 39 amino acids. Synacthen (tetracosactide) contains only the first 24 amino acids, which are the part needed to stimulate the adrenal glands to produce cortisol.
 

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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