Adrenocorticotropin (ACTH) is a hormone produced by the pituitary gland, a small structure at the base of the brain. It signals the adrenal glands, located on top of each kidney, to regulate the body’s response to various internal and external signals.
The Role of Adrenocorticotropin
ACTH travels through the bloodstream to the adrenal glands, acting on their outer part, the adrenal cortex. This stimulation prompts the adrenal cortex to produce and release cortisol, a steroid hormone. Cortisol affects nearly every organ and tissue, managing stress responses, regulating metabolism of fats, proteins, and carbohydrates, and suppressing inflammation. It also helps maintain blood pressure and blood sugar levels.
Regulation and the HPA Axis
The body’s control system for ACTH involves the Hypothalamic-Pituitary-Adrenal (HPA) axis. This axis begins in the hypothalamus, which releases corticotropin-releasing hormone (CRH) in response to various stimuli. CRH then travels to the pituitary gland, prompting it to release ACTH.
ACTH signals the adrenal glands to produce cortisol. A key aspect of this system is the negative feedback loop, which acts like a thermostat to maintain balance. When cortisol levels in the blood rise, they signal back to both the hypothalamus and the pituitary gland. This feedback inhibits CRH and ACTH release, preventing cortisol overproduction.
Conditions Related to Abnormal Levels
When ACTH and cortisol balance is disrupted, various health conditions can arise, characterized by excessively high or unusually low hormone levels.
High ACTH Levels
Excessive ACTH production often leads to Cushing’s disease, a type of Cushing’s syndrome. This condition typically results from a benign pituitary tumor that produces too much ACTH, causing the adrenal glands to release high cortisol levels. Symptoms include rapid weight gain, particularly around the trunk and face (“moon face”), and a fatty lump between the shoulders (“buffalo hump”). Individuals may also experience thin, fragile skin, easy bruising, reddish-purple stretch marks, and muscle weakness. Other symptoms include high blood pressure, elevated blood sugar, and bone loss.
Low ACTH Levels
Conversely, insufficient ACTH production can result in secondary adrenal insufficiency, leading to a cortisol deficiency. This occurs when the pituitary gland does not produce enough ACTH, which means the adrenal glands are not adequately stimulated. Causes can include pituitary tumors, surgery or radiation therapy involving the pituitary, or prolonged use of certain steroid medications that suppress ACTH production. Symptoms frequently include fatigue, generalized weakness, unintended weight loss, nausea, vomiting, decreased appetite, and low blood pressure. Unlike some other adrenal conditions, hyperpigmentation (darkening of the skin) is generally absent.
Medical Testing and Therapeutic Use
Medical professionals utilize ACTH in both diagnostic procedures and, in certain situations, as a therapeutic agent. These applications leverage its specific role in the endocrine system to assess function or manage various conditions.
Diagnostic Use
The ACTH stimulation test, also known as the cosyntropin stimulation test, is a common diagnostic tool. During this test, doctors administer a synthetic form of ACTH, called cosyntropin, typically through an injection into a muscle or vein. Blood samples are then collected at specific intervals, often 30 and 60 minutes after the injection, to measure the adrenal glands’ cortisol response. A normal rise in cortisol levels indicates healthy adrenal gland function, while a blunted or absent response helps diagnose adrenal insufficiency.
Therapeutic Use
Synthetic ACTH can also be employed in the treatment of a few specific medical conditions. Its use is largely due to its ability to stimulate endogenous cortisol production, which has anti-inflammatory and immunomodulatory effects. Examples include the treatment of infantile spasms, a type of seizure disorder in babies, and in some cases of multiple sclerosis to manage acute exacerbations. It has also found application in certain rheumatic disorders and skin conditions, where its anti-inflammatory properties can help alleviate symptoms.