ACTH plasma refers to a blood test that measures the level of adrenocorticotropic hormone (ACTH) circulating in your blood. ACTH is a hormone produced by the pituitary gland, a small structure at the base of the brain, and its main job is to tell your adrenal glands (which sit on top of your kidneys) to produce cortisol. Normal morning levels fall between 9 and 52 pg/mL. The test is typically ordered alongside a cortisol test to figure out whether symptoms like unexplained weight changes, fatigue, or blood pressure problems are coming from the pituitary gland or the adrenal glands.
What ACTH Does in the Body
ACTH is part of a communication chain between your brain and your adrenal glands known as the HPA axis: the hypothalamus signals the pituitary, and the pituitary releases ACTH, which travels through the bloodstream to the adrenal glands. There, it triggers the production and release of cortisol from a specific layer of the adrenal cortex. Cortisol affects nearly every organ system, regulating blood sugar, blood pressure, inflammation, and your body’s response to stress.
The system has a built-in thermostat. When cortisol levels rise high enough, the hypothalamus and pituitary detect this and reduce ACTH output. When cortisol drops, ACTH ramps back up. This feedback loop keeps cortisol within a healthy range throughout the day. ACTH also follows a natural daily rhythm, peaking in the early morning and falling to its lowest point late at night. That’s why timing matters when the test is ordered.
Why the Test Is Ordered
A plasma ACTH test helps pinpoint the source of a cortisol problem. Cortisol that’s too high or too low can cause a wide range of symptoms, but knowing the cortisol level alone doesn’t explain why it’s abnormal. Pairing ACTH with cortisol narrows the possibilities significantly.
Common symptoms that prompt testing include unexplained weight gain (especially around the midsection and face), muscle weakness, thinning skin, high blood pressure, chronic fatigue, darkening of the skin, dizziness, or persistent low blood pressure. If your provider suspects a problem with either the pituitary or adrenal glands, this test is one of the first steps.
What High ACTH Levels Mean
High ACTH paired with high cortisol points toward Cushing’s disease, which is caused by a small, usually noncancerous tumor on the pituitary gland (called a pituitary adenoma) that churns out excess ACTH. The extra ACTH forces the adrenal glands to overproduce cortisol. In rarer cases, a tumor growing in another organ, such as the lungs, can produce ACTH on its own. This is called ectopic ACTH production, and it also drives cortisol levels up.
High ACTH paired with low cortisol suggests the adrenal glands themselves aren’t responding properly. This pattern is the hallmark of primary adrenal insufficiency (Addison’s disease). The pituitary detects low cortisol and keeps sending more ACTH, but the damaged adrenal glands can’t keep up.
What Low ACTH Levels Mean
Low ACTH with high cortisol typically means something other than the pituitary is producing the excess cortisol. The two most common causes are an adrenal gland tumor making cortisol independently, or long-term use of corticosteroid medications like prednisone. In both cases, the high cortisol signals the pituitary to shut down ACTH production because, from the brain’s perspective, there’s already more than enough cortisol in the system.
Low ACTH with low cortisol points to a pituitary problem, a condition called hypopituitarism. A pituitary tumor, surgery, radiation, or other damage can prevent the gland from producing enough ACTH, which in turn leaves the adrenal glands without their primary signal to make cortisol.
How To Prepare for the Test
Because ACTH peaks in the early morning, blood draws are usually scheduled between 7 and 9 a.m. to capture levels at their natural high point. Your provider may ask you to fast for about 6 hours before the draw, and in some cases to eat high-carbohydrate foods in the 12 to 24 hours beforehand. You may also need to temporarily stop taking hydrocortisone or other corticosteroid medications, since these directly suppress ACTH and would skew the results. Always confirm specific instructions with the lab or your provider, as preparation requirements can vary.
Stress, illness, and certain medications can also influence results. Sedatives, opioid pain medications, and some antifungal drugs have been shown to blunt the HPA axis or interfere with cortisol production, which indirectly affects ACTH readings. If you’re taking any of these, let your provider know before the test.
Why Sample Handling Matters
ACTH has a reputation for being fragile once it’s outside the body, which is why the test specifically uses plasma (the liquid portion of blood collected in a special chilled tube) rather than serum. Most laboratories require the blood sample to be kept cold and processed quickly. A 2024 review of lab practices across 33 French university hospitals found that 76% required refrigerated transport of ACTH samples, while 24% accepted room temperature handling.
Recent research suggests ACTH is more stable than previously thought, remaining reliable in standard collection tubes for about 6 hours at room temperature and at least 8 hours when refrigerated. Still, rapid processing is the standard recommendation. If your lab results come back unexpected, poor sample handling is one factor your provider may consider before repeating the test.
Reading Your Results in Context
A single ACTH number doesn’t tell the full story. The test is almost always interpreted alongside a cortisol level drawn at the same time, and sometimes alongside additional tests like a dexamethasone suppression test or an ACTH stimulation test, which challenge the system to see how it responds. Reference ranges can also vary slightly between laboratories, so a result of 8 pg/mL at one lab might be flagged as low while another lab’s range starts at 6.
Time of day, stress level, recent illness, and medications all shape what a “normal” result looks like for you. The combination of ACTH and cortisol values, along with your symptoms, is what allows a provider to distinguish between conditions that can look remarkably similar on the surface but require very different treatments.