The Synacthen test shows whether your adrenal glands can produce enough cortisol when they get the signal to do so. A doctor uses it when there is a suspicion of a reduced adrenal function. It is not a test you do yourself at home.
Honestly? This is exactly the topic that causes a lot of confusion online. A one-off cortisol measurement and the Synacthen test are often mixed up, even though they measure something quite different.
This article explains what the Synacthen test is, how it works, how you prepare and what the result can mean. It also covers why a single cortisol test is usually something different from this clinical test.
What is the Synacthen test?
The Synacthen test is an examination in which you are given a synthetic form of the hormone ACTH, after which a doctor measures how much cortisol your adrenal glands produce in response. This assesses the reserve capacity of your adrenal glands, not just your cortisol at that one moment.
Your adrenal glands are two small glands that sit on top of your kidneys. They produce cortisol, a hormone involved in your metabolism, your blood pressure and how you handle stress. Production is driven by ACTH, a hormone from your pituitary gland.
For the test the doctor uses tetracosactide, a synthetic copy of ACTH (brand name Synacthen). It mimics the natural signal from your brain and puts your adrenal glands to work. In practice the short Synacthen test is used most often, and it takes about an hour.
How does the Synacthen test work?
The short Synacthen test takes about an hour and is not very demanding. You get a small cannula, a baseline sample is taken, you receive the injection, and after 30 and sometimes 60 minutes another sample is taken. After that you can get on with your day.
- Cannula - a small needle is placed in your arm, so you only need to be pricked once.
- Baseline - blood is drawn first to determine your cortisol before stimulation.
- The injection - the tetracosactide is given through the cannula or into a muscle.
- Follow-up samples - blood is drawn again after 30 minutes, and often after 60 minutes too.
- Finishing up - the needle comes out and you can usually go home straight away.
Alongside the short test there is a longer version over several hours. It is used less often and only in specific situations, for example to separate a cause in the adrenal gland from one in the pituitary (Siampanopoulou, 2023).
How do you prepare for the Synacthen test?
A few practical points apply to the Synacthen test. The test usually happens in the morning, some medications can affect the result, and significant stress just beforehand is better avoided. Your doctor tells you exactly what is needed in your situation.
- Timing - the test is often done in the morning, because your cortisol is naturally highest then.
- Medication - corticosteroids such as prednisone or hydrocortisone can affect the result. Never stop these on your own, but discuss it with your doctor in advance.
- Fasting - you usually do not need to fast for the Synacthen test, unless your doctor says so because other values are measured at the same time.
- Stress - try to start the test calmly, because stress naturally raises your cortisol.
What does the Synacthen test result mean?
With a healthy adrenal function your cortisol rises clearly after the injection. If that rise does not happen, it can point to a reduced adrenal function. The Synacthen test is the most widely used test to assess that response (Siampanopoulou, 2023).
Many laboratories regard a peak value of around 420 to 550 nmol/L after stimulation as a normal response. The exact limit differs per laboratory and method, so your doctor always reads the result within your situation.
A meta-analysis showed that the test is suitable for confirming a deficiency, but less so for fully ruling it out (Ospina, 2016). An abnormal result is therefore a reason to look further, not an endpoint.
Primary and secondary adrenal insufficiency
Sometimes the problem lies in the adrenal glands themselves. If they barely respond to stimulation, that fits a primary adrenal insufficiency, such as Addison's disease.
Sometimes the cause lies higher up, in a pituitary gland that produces too little ACTH. The adrenal glands then become under-stimulated. Distinguishing the two often needs further testing, because the Synacthen test does not always separate these causes.
Is a one-off cortisol test or self-test worthwhile?
A one-off cortisol measurement shows how high your cortisol is at that moment. It says nothing about the reserve capacity of your adrenal glands. So a single test or self-test cannot confirm and cannot rule out adrenal insufficiency.
Say you measure a low cortisol value in the morning. You still do not know why it is low. Can your adrenal glands not produce it? Is there no signal from your brain? Or was it chance on a quiet morning? The Synacthen test is designed to answer exactly that question.
| One-off cortisol measurement (blood or saliva) | Synacthen test (ACTH stimulation test) | |
|---|---|---|
| What it measures | Your cortisol at a single moment | How your adrenal glands respond to stimulation |
| What it can show | A snapshot of your cortisol level | Something about your adrenal reserve capacity |
| What it cannot do | Explain why a value is low | Fully rule out a pituitary problem on its own |
| Where it usually belongs | Orientational, often within a broader blood test | Clinical diagnostics, in hospital |
There is a lot of online attention for "adrenal fatigue". A systematic review, however, found no scientific basis that this is an existing medical condition (Cadegiani & Kater, 2016). Persistent, serious complaints therefore belong with your GP, not with a self-test.
If you still want to have your cortisol measured, you can do so at Vital Check as a single value: cortisol. Just know what such a snapshot can and cannot tell you. If fatigue is your main complaint, read which blood values can explain fatigue, or see which hormones you can have tested in a blood test. More about cortisol itself is in cortisol: the stress hormone explained.
What are the side effects of the Synacthen test?
The side effects of the Synacthen test are usually mild. Most people notice little, and you are under medical supervision during the test. Possible, generally mild reactions are:
- A warm feeling or flushing in your face, just after the injection.
- Mild nausea or a metallic taste in your mouth.
- Brief palpitations or a rushed feeling.
An allergic reaction to the agent is rare. Because you are supervised, help is available right away if it does happen. Many people mainly find the test boring, since you are mostly waiting.
In closing
For me the most useful takeaway is the difference between measuring and stimulating. A one-off cortisol value is a snapshot, while the Synacthen test looks at what your adrenal glands can actually do.
Wondering whether your complaints have to do with your adrenal glands? Discuss the Synacthen test specifically with your GP. That often achieves more than doing a one-off cortisol test on your own initiative.
Frequently asked questions
Do you need to fast for the Synacthen test?
You usually do not need to fast for the Synacthen test. Sometimes your doctor does ask for it, for example because other blood values are measured at the same time. Always follow the instruction you get from your doctor.
How long does the Synacthen test take?
The short Synacthen test takes about an hour, including the samples after 30 and 60 minutes. The longer version can take several hours and is used less often.
Can I do the Synacthen test at home?
No. The Synacthen test requires an injection and blood samples under medical supervision, so it takes place in a hospital or clinic. A home test at most measures your cortisol at a moment, not the response to stimulation.
Does the Synacthen test hurt?
Most people only feel the prick of the cannula. The injection itself goes through that needle. Some people briefly feel a warm sensation after it is given.
What is the difference between the Synacthen test and a regular cortisol test?
A regular cortisol test measures your cortisol at a single moment. The Synacthen test measures how your adrenal glands respond after they are stimulated, which says something about their reserve capacity.
References
- Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review. BMC Endocr Disord. 2016;16:48. PMID: 27557747.
- Ospina NS, Al Nofal A, Bancos I, et al. ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2016;101(2):427-434. PMID: 26649617.
- Siampanopoulou V, Tasouli E, Angelousi A. Diagnostic strategies in adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2023;30(3):141-153. PMID: 37036291.
Every blood test result at Vital Check includes a professional assessment from a BIG-registered doctor. A blood test does not make a diagnosis. For treatment decisions, discuss your results with your GP.
Frequently asked questions
Do you need to fast for the Synacthen test?
You usually do not need to fast for the Synacthen test. Sometimes your doctor does ask for it, for example because other blood values are measured at the same time. Always follow the instruction you get from your doctor.
How long does the Synacthen test take?
The short Synacthen test takes about an hour, including the samples after 30 and 60 minutes. The longer version can take several hours and is used less often.
Can I do the Synacthen test at home?
No. The Synacthen test requires an injection and blood samples under medical supervision, so it takes place in a hospital or clinic. A home test at most measures your cortisol at a moment, not the response to stimulation.
Does the Synacthen test hurt?
Most people only feel the prick of the cannula. The injection itself goes through that needle. Some people briefly feel a warm sensation after it is given.
What is the difference between the Synacthen test and a regular cortisol test?
A regular cortisol test measures your cortisol at a single moment. The Synacthen test measures how your adrenal glands respond after they are stimulated, which says something about their reserve capacity.
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