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First this lesson will review how and why an ACTH stimulation test is performed. Then, interpretations of high or low values, as well as limitations of the test will be discussed.

Review of Adrenal Glands

Ever heard of the ‘stress hormone’? It’s a signal in your body that prepares you to deal with stress, like in fight or flight situations.

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However, we hear about it mostly because of chronic stress, where the hormone gets too abundant in our bodies and starts wreaking havoc.The adrenal glands are two small, fatty glands that sit on top of the kidneys. Their primary purpose is to secrete different hormones to help regulate the body’s most critical functions. These little glands are famously known for producing adrenaline, but they also make hormones that regulate our blood pressure, fat storage, and blood sugars.

These are known as corticosteroids like cortisol, aka ‘the stress hormone’.The adrenal glands receive signals to make this hormone from the pituitary gland in the form of another hormone, ACTH (Adrenocorticotrophic releasing hormone), which receives signals from the hypothalamus, a part of the brain. So, the hypothalamus sends signals to the pituitary gland, which sends ACTH to the adrenal gland, which then makes corticosteroids.These two glands coordinate with each other to help keep us alive and healthy through a variety of situations, and to protect our bodies from becoming swamped with too many hormones.But like so many bodily processes, things can go wrong. In diagnosing many diseases of the adrenal glands, doctors use an ACTH stimulation test which studies the Hypothalamic-Pituitary-Adrenal (HPA) system, one of the primary drivers of corticosteroid production. Before we get into how to interpret results, let’s review the test itself.

Basic Concepts of ACTH Stimulation Testing

The ACTH stimulation test relies on negative feedback, where some kind of stimulus is used to get a reaction from the body natural regulation of itself to maintain ideal levels. It’s sort of the scientific equivalent of poking something with a stick to see what it does to compensate. It’s provoking a response as a way of testing out function.

The Hypothalamic-Pituitary-Adrenal (HPA) system
HPA axis and negative feedback

The ACTH stimulation test primarily uses the synthetic form of ACTH, which is injected into the patient during the test.

The expectation is that the body will react to the additional ACTH by producing cortisol from the adrenal cortex. After about an hour, the levels of cortisol and a related hormone in the adrenal glands, aldosterone, are measured in the blood or urine.

Test Results


ACTH stimulates the production of cortisol by acting on the adrenal cortex. If the patient is properly prepared for the procedure, you can expect to see a rise in the blood and urine cortisol content shortly thereafter. The cortisol level should rise above 20 mcg/dl, which would indicate that the adrenal tissue is functional and responsive to ACTH.

This is a lot like nudging someone when they are asleep, you would expect them to wake up, which indicates that they are okay.


However, what happens when this is not true? ACTH should stimulate cortisol production, regardless of the health of the pituitary gland, so if appropriate ACTH was given and there is no rise in cortisol levels, the adrenal cortex is assumed to be the source of disease.This result narrows the differential diagnoses to diseases such as Addison’s disease and adrenal insufficiency, as well as diseases associated with hypocortisolism (low cortisol levels). To continue the analogy, this would be like nudging someone while asleep, but they do not wake up.

To many people, this would be a response that would cause concern.


Conversely, if the levels of cortisol rise significantly above 20 mcg/dl, the pituitary gland itself may have a disease such as hypopituitarism (low hormone secretion). If the patient has come in with low blood pressure and low blood sugar, these are symptoms of low cortisol.

If their cortisol spikes overly high in the ACTH test, it’s likely that the issue is coming from the pituitary gland (or further upstream at the hypothalamus).This would be like our analogy of nudging someone when asleep, only this time the person springs up and slugs you in the face. This would also indicate a problem, but with a different cause.

Limitations of Accuracy

The ACTH stimulation test is excellent for testing the negative feedback pathway in the HPA axis, however, because this negative feedback affects multiple hormone levels (both ACTH and CRHP, known as corticotropin-releasing hormone) the patient will need extra testing to determine exactly what and where the problem is. Its a lot like GPS, you need to have several signals to help triangulate where something is.ACTH levels can be taken before the stimulation test in order to see if that level is high or low to help compare.

If one has a high ACTH and the adrenal tissue responds to the test with a sufficient amount of cortisol production, then that can be a sign of an pituitary tumor (most commonly an adenoma). If the ACTH is low and the response from the adrenal tissue is high, then that can be a sign of damage to the pituitary gland or hypothalamus.However, how can you tell which? Naturally we would want to test the CRHP level, right? Actually, the only way to test that level is an invasive test to sample the hypothalamus which is very difficult. The most non-invasive way is a CRHP stimulation test which would test the negative feedback between the hypothalamus and pituitary gland, which is the same idea as the ACTH stimulation test.

Lesson Summary

The ACTH stimulation test studies the Hypothalamic-Pituitary-Adrenal (HPA) system to help to assess the health of the hypothalamus, and adrenal and pituitary glands by testing hormone production. It relies on negative feedback, or using a stimulus to provoke a response to the body’s regulatory systems, to help find where any problem might be.By adding synthetic ACTH to the body, the adrenal glands should produce 20 mcg/dl or so of cortisol.

If production is low, the problem is likely in the adrenal glands. If production is high, the problem is likely in the pituitary gland.When the ACTH stimulation test is used by itself, doctors may need other tests to hone in the exact area of the problem. A similar test known as the CRHP stimulation test works in a similar way to help narrow down the diagnosis.’Medical Disclaimer: The information on this site is for your information only and is not a substitute for professional medical advice.

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