Adrenocorticotropic Hormone (ACTH) is a peptide signaling molecule produced by the pituitary gland. This hormone acts as a messenger, relaying a signal from the brain to the adrenal glands, which sit atop the kidneys. Its primary function is to regulate the release of cortisol, governing the body’s metabolic response to stress. Measuring ACTH levels offers insight into the communication between these endocrine organs and helps assess overall hormonal balance.
The Role of ACTH in the Body
ACTH is synthesized by specialized cells, called corticotrophs, within the anterior lobe of the pituitary gland. Its production is triggered by corticotropin-releasing hormone (CRH) released from the hypothalamus. ACTH then travels through the bloodstream to its main target, the adrenal cortex, the outer layer of the adrenal glands.
ACTH stimulates the adrenal cortex to produce and release glucocorticoids, primarily cortisol. Cortisol is a steroid hormone that influences metabolism, blood pressure, blood sugar, and immune function. The concentration of cortisol in the blood provides feedback to both the hypothalamus and the pituitary gland. High cortisol levels signal the brain to reduce the output of CRH and ACTH, maintaining hormonal equilibrium.
Understanding ACTH Testing and Normal Ranges
Testing for ACTH involves a blood draw, typically performed in the morning, because the hormone’s concentration naturally fluctuates throughout the day. ACTH levels follow a distinct diurnal rhythm, peaking around 8:00 AM and falling to their lowest point late in the evening. This circadian variation makes accurate timing of the blood sample necessary for a meaningful result.
The ACTH concentration is measured in picograms per milliliter (pg/mL) of blood. A typical reference range for a healthy adult in a morning sample is between 6 and 50 pg/mL, though this range can vary depending on the specific laboratory. Interpretation of the ACTH level must always be considered alongside a simultaneous measurement of cortisol to determine where a potential problem lies in the hormonal chain.
Causes and Implications of Elevated ACTH Levels
Abnormally high ACTH levels occur when the pituitary gland attempts to compensate for low cortisol production or when the pituitary itself overproduces the hormone. Primary Adrenal Insufficiency, or Addison’s Disease, is a common scenario. Here, damaged adrenal glands cannot manufacture enough cortisol despite receiving a strong signal from the pituitary.
The resulting lack of negative feedback causes the pituitary to continuously release excessive ACTH. Because ACTH is derived from a precursor molecule that also yields Melanocyte-Stimulating Hormone (MSH), chronically high ACTH levels can cause hyperpigmentation, or darkening of the skin. Patients with Addison’s disease often exhibit this skin darkening, along with fatigue and weakness due to cortisol deficiency.
Elevated ACTH can also be the cause, rather than the result, of a hormonal imbalance. Cushing’s Disease, a specific type of Cushing’s Syndrome, is caused by a benign pituitary tumor that autonomously secretes excessive ACTH. This excess ACTH overstimulates the adrenal glands, leading to dangerously high cortisol levels. In rare cases, a tumor located outside the pituitary (Ectopic ACTH production), such as in the lung or pancreas, can produce ACTH, leading to signs of cortisol excess like weight gain, muscle weakness, and easy bruising.
Causes and Implications of Suppressed ACTH Levels
Low or suppressed ACTH levels indicate that the body is receiving excessive cortisol or that the pituitary gland is not functioning correctly. The most frequent cause is the long-term use of high-dose steroid medications, such as prednisone, used to treat inflammatory conditions. These exogenous corticosteroids mimic natural cortisol, signaling the pituitary to reduce ACTH production.
This suppression can lead to Secondary Adrenal Insufficiency, where the adrenal glands shrink and lose their ability to produce cortisol due to lack of stimulation. If steroid medication is suddenly stopped, the suppressed pituitary and atrophied adrenal glands cannot immediately resume normal function. This leaves the body short of cortisol.
Low ACTH paired with low cortisol may also signal a problem within the pituitary gland or the hypothalamus, known as Secondary or Tertiary Adrenal Insufficiency. Conditions like pituitary tumors, surgery, or radiation can damage ACTH-producing cells, leading to an inadequate signal to the adrenals. Without ACTH stimulation, the adrenal glands do not produce enough cortisol, resulting in symptoms like chronic fatigue, weakness, and low blood pressure.