ACTH Stimulation Test
An ACTH stimulation test assesses how well the adrenal glands respond when prompted to make cortisol. It is a dynamic test that helps clinicians find out whether the adrenal glands can rise to the occasion when they receive their normal signal, rather than relying on a single resting measurement.
What the test assesses
Cortisol is a hormone made by the adrenal glands, and its production is normally driven by adrenocorticotropic hormone (ACTH) from the pituitary gland. In the test, a form of ACTH is given, and cortisol is measured before and after to see how much the adrenal glands respond. A healthy adrenal gland should raise cortisol meaningfully when stimulated; a weak or absent rise suggests the glands cannot respond as they should.
The test focuses on the responsiveness of the adrenal glands themselves rather than on the strength of the pituitary signal. By supplying the ACTH directly, it removes the question of whether the pituitary is sending enough signal and instead asks whether the adrenal glands can act on it. This makes it especially useful for sorting out where a cortisol problem might lie.
Primary versus secondary adrenal insufficiency
When the adrenal glands themselves are the problem, cortisol production is low even with a strong stimulating signal; this is often called primary adrenal insufficiency. When the issue lies higher up, with too little ACTH reaching the glands over time, the pattern is described as secondary. The stimulation test contributes to telling these apart, although a clinician interprets it alongside an ACTH measurement and the clinical picture rather than from the cortisol response alone.
Why a clinician might order it
This test is mainly used when there is concern about adrenal insufficiency, a condition in which the adrenal glands do not make enough cortisol. Symptoms such as fatigue, weakness, low blood pressure, and poor appetite can prompt evaluation. The test helps clarify whether the adrenal glands are capable of producing cortisol when stimulated, which is central to recognizing and characterizing adrenal insufficiency.
How the test works
The test follows a timed protocol. A baseline blood sample for cortisol is drawn first, then a dose of synthetic ACTH is given, usually by injection. One or more further blood samples are taken at set times afterward to measure how much cortisol rose in response. Comparing the baseline level with the stimulated levels shows whether the adrenal glands mounted an adequate response. The specific timing of the draws is part of the protocol and matters to interpretation, which is why the test is performed in a clinical setting under supervision.
How to prepare
Preparation depends on the protocol and the reason for testing. Because cortisol follows a daily rhythm, the test is often performed at a particular time of day. Several medications, including steroid medications, can affect cortisol levels and the response, so a complete medication list is important. Stress and acute illness can also influence results, and the testing team will give specific instructions to follow.
What can affect the result
- Steroid medications: recent or ongoing steroid use can alter both baseline cortisol and the response.
- Time of day: cortisol follows a daily rhythm, so timing is standardized within the protocol.
- Acute illness and stress: these can raise cortisol and change how the result is read.
- Estrogen-containing medications: these can affect the proteins that carry cortisol in the blood, which a clinician takes into account.
- Protocol details: the dose form and the timing of the draws differ between protocols and influence interpretation.
How it fits with other cortisol tests
The ACTH stimulation test rarely stands alone. A clinician usually pairs it with a baseline cortisol level, often drawn in the morning to align with the daily rhythm, and with an ACTH measurement that shows how strong the pituitary signal is. Read together, these tests help separate a problem in the adrenal glands themselves from one rooted higher up in the pituitary. Where the question is the opposite, whether the body is making too much cortisol rather than too little, different tests of total output or suppression are used instead. Choosing among these tools depends on the suspected direction of the problem, and the stimulation test is selected specifically when adrenal responsiveness is in question.
Because the test reflects a single timed challenge, its result is interpreted with the same caution as any one measurement. Medications, the time of day, and recent illness can all shape the response, so a clinician weighs the numbers against the full clinical picture and may repeat or supplement the test when the answer is not clear-cut.
How results are generally interpreted
Results are read by comparing cortisol after stimulation with the baseline and with the rise expected from healthy adrenal glands.
- Adequate cortisol rise: the adrenal glands responded as expected, which makes significant adrenal insufficiency less likely.
- Blunted or absent rise: the adrenal glands did not respond well, a pattern seen in adrenal insufficiency that usually prompts further testing to identify the cause.
- Borderline rise: may reflect timing, medications, or partial impairment and often leads to repeat or additional testing.
Illustrative interpretation patterns
The patterns below are illustrative only; exact thresholds vary by laboratory, assay, and the specific protocol used. Always rely on the interpretation that accompanies your own test and a clinician's assessment.
| Response | Illustrative meaning |
|---|---|
| Cortisol rises adequately after ACTH | suggests responsive adrenal glands |
| Little or no cortisol rise | prompts evaluation for adrenal insufficiency |
| Equivocal rise | may reflect timing or medication; often repeated |
Related tests
This test is often interpreted alongside a baseline cortisol measurement and an ACTH level. When the question is instead whether cortisol can be turned down rather than turned up, a different dynamic test is used; a 24-hour urine cortisol test may be used to assess total daily cortisol output in other settings. See the blood tests index, the hormones index for background on cortisol and ACTH, and the conditions index for adrenal insufficiency. The guides index offers help reading results.
Frequently asked questions
What does the test actually check?
It checks whether the adrenal glands can raise cortisol when given a stimulating signal, which helps in evaluating adrenal insufficiency.
Why is cortisol measured more than once?
A baseline sample and one or more samples after the ACTH dose are needed so the rise in cortisol can be compared against what healthy adrenal glands would produce.
Can my medications affect the result?
Yes. Steroid medications and several others can change cortisol levels and the response, which is why a complete medication list is important. Do not change medications on your own before the test.
How does a stimulation test differ from a suppression test?
A stimulation test checks whether the adrenal glands can raise cortisol when prompted, while a suppression test checks whether cortisol can be turned down by a suppressing signal. They probe opposite questions.
Can this test tell where the cortisol problem lies?
It contributes to that, helping distinguish a problem in the adrenal glands from one higher up, but a clinician interprets it alongside an ACTH level and the clinical picture.
Why is the test done under supervision?
It involves an injection and timed blood draws on a set schedule, so it is carried out in a clinical setting where the protocol can be followed precisely.
Sources
- MedlinePlus. Cortisol Test. https://medlineplus.gov/lab-tests/cortisol-test/
- MedlinePlus. Endocrine Diseases. https://medlineplus.gov/endocrinediseases.html
- Endocrine Society. https://www.endocrine.org/