Adrenocorticotropic hormone (ACTH) is a peptide hormone produced by the pituitary gland, a small organ located at the base of the brain. Its primary action is to travel through the bloodstream to the adrenal glands, which sit atop the kidneys. There, ACTH stimulates the outer layer of the adrenal gland to begin producing and releasing cortisol.
The Role of ACTH in Controlling Cortisol
ACTH functions as the middle step in the Hypothalamic-Pituitary-Adrenal (HPA) axis. This axis begins in the hypothalamus, which releases corticotropin-releasing hormone (CRH) to signal the pituitary gland. The pituitary then releases ACTH, which acts on the adrenal cortex to initiate the production of cortisol.
Cortisol is a glucocorticoid hormone that affects nearly every tissue in the body, helping to regulate metabolism by controlling the use of fats, proteins, and carbohydrates. It also helps to regulate blood pressure and modulates the body’s inflammatory and immune responses. Once cortisol levels rise in the blood, they signal back to the hypothalamus and the pituitary gland to reduce the release of CRH and ACTH, completing a negative feedback loop.
Understanding the ACTH Test and Normal Ranges
An ACTH test is performed in conjunction with a cortisol test to evaluate the HPA axis function. The timing of the blood collection is important because ACTH levels naturally fluctuate throughout the day, following a pattern called the diurnal rhythm. ACTH levels are highest in the early morning, usually peaking around 8:00 a.m., and then gradually decline to their lowest point late in the evening or around midnight.
For a blood sample taken between 7:00 a.m. and 10:00 a.m., a typical reference range for ACTH in adults is 7.2 to 63.3 picograms per milliliter (pg/mL) or 10 to 60 pg/mL. The corresponding late-night value should be significantly lower, often dropping to below 10 pg/mL. Factors like physical or emotional stress, pregnancy, and the use of certain medications, such as synthetic glucocorticoids, can temporarily alter these levels and must be considered during interpretation. The collection time must be precisely noted for accurate interpretation by a healthcare provider.
Interpreting Results That Are Too High
An ACTH level that is consistently above the normal morning range indicates that the pituitary gland is attempting to over-stimulate the adrenal glands. This pattern is frequently a compensatory response to the adrenal glands not producing enough cortisol, a condition known as primary adrenal insufficiency (Addison’s disease).
High ACTH can also be the underlying cause of high cortisol, which is seen in a condition called Cushing’s disease. This occurs when a benign tumor in the pituitary gland, called an adenoma, excessively secretes ACTH, driving the adrenal glands to overproduce cortisol. Less commonly, very high ACTH levels result from an ectopic source, such as a non-pituitary tumor, often in the lung, that independently secretes ACTH. The distinction between these causes—high ACTH due to adrenal failure versus high ACTH driving cortisol overproduction—is determined by simultaneously measuring the corresponding cortisol level.
Interpreting Results That Are Too Low
A significantly suppressed ACTH level usually signals that the pituitary gland is not releasing enough of the hormone. This low level can be a result of the negative feedback loop being overwhelmed by an excessive amount of cortisol from an outside source. The most common cause of this is the long-term use of high-dose corticosteroid medications, such as prednisone, which the body recognizes as cortisol.
The excess cortisol from the medication suppresses the pituitary’s production of ACTH. Low ACTH levels are also characteristic of Cushing’s syndrome caused by an adrenal tumor that autonomously produces high amounts of cortisol. In this case, the high cortisol feeds back to the pituitary, switching off ACTH secretion. Finally, a low ACTH level may also indicate hypopituitarism, where damage or a tumor in the pituitary gland directly impairs its ability to produce the hormone.