Adrenocorticotropic Hormone (ACTH)

Adrenocorticotropic hormone (ACTH) is produced by the anterior lobe of the pituitary gland. ACTH production is usually associated with stressful life events, because it is involved in the production of cortisol. Cortisol, in turn, is associated with the stimulation of the adrenal gland, which produces adrenalin when a person is in a "fight or flight" situation, that is, the presence of a threat, such as a predator or other aggressor, which causes a person instinctively to seek to run away or to engage in self-defensive combat. When a person’s body produces too much or too little ACTH, a variety of disorders may develop. These include Addison’s disease (which is a colloquial term for an adrenal insufficiency) and Cushing’s disease syndrome (a syndrome characterized by elevated adrenal output). ACTH is also used as a medical intervention, as a means of assessing whether or not a patient’s adrenal system is in proper working order.

Background

ACTH levels in the body usually have an inverse relationship to levels of cortisol, which is crucial for many bodily functions. For this reason, physicians often administer ACTH tests as a way of assessing whether or not the body’s cortisol levels are appropriate. In order for ACTH to be produced, the hypothalamus first releases corticotropin-releasing hormone (CRH). This tells the pituitary gland to begin producing ACTH. ACTH is released in bursts, so its levels in the body rise and fall at different times throughout the day. One result of this is that levels of ACTH are connected to the body’s circadian rhythms. Circadian rhythms are changes in behavior and physiology in response to changing levels of light and darkness throughout the day and night.

ACTH can be thought of as the "traffic cop" regulating (directly or indirectly) many of the body’s integral processes through its ability to affect cortisol levels—when the body secretes ACTH, this results in the production of cortisol by the adrenal glands. Cortisol is important because it is involved in so many different functions. Cortisol levels are used to regulate some processes within the body’s immune system, as well as controlling levels of sugar in the blood. Cortisol also plays a role in how the body metabolizes fats, carbohydrates, and proteins. When a person’s levels of cortisol are lower than they should be, this will sometimes manifest through a feeling of perpetual fatigue or lethargy. In fact, cortisol is responsible for helping people to wake up in the morning, get out of bed, and have the energy necessary to start their daily routine. Cortisol levels tend to reach their highest point at about eight o’clock in the morning in healthy individuals. On the other hand, cortisol is also versatile enough that in addition to helping people get going in the morning, it can also cause certain functions to shut down as a response to stress, so that the body’s energy can be concentrated on the tasks that are essential for survival. For example, cortisol fluctuations can cause the reproductive system to be partially shut down in order for the body to concentrate on fighting illness or on dealing with other sources of stress.

Overview

Many people are familiar with ACTH because of its use in what is known as the ACTH stimulation test. Endocrinologists—doctors who specialize in the glandular and hormonal systems of the body—will sometimes order an ACTH stimulation test as a way of determining whether a patient’s ability to produce cortisol in response to ACTH is functioning properly. In order to perform the test, doctors will administer a small amount of synthetically produced ACTH. Because the body’s normal response to the production of ACTH is to produce cortisol, in a healthy patient the result of the ACTH stimulation test will be an increase in the body’s cortisol levels. Doctors will therefore measure the patient’s cortisol levels before and after the administration of the ACTH stimulation test, to see if there is any change in cortisol levels that could be attributed to the ACTH stimulation test’s introduction of synthetic ACTH into the patient’s body. When the ACTH stimulation test identifies an adrenal insufficiency, the test can also determine if the cause of this problem is in the pituitary gland (where natural ACTH is produced) or in the adrenal glands themselves. The ACTH stimulation test is much better at detecting problems with the adrenal glands, also known as primary adrenal insufficiency. Secondary adrenal insufficiency (i.e., problems with the pituitary gland) are more difficult for the ACTH stimulation test to conclusively identify. If doctors suspect secondary adrenal insufficiency after looking at the results of the ACTH stimulation test, they may order additional tests to make sure they have correctly diagnosed the patient’s condition.

In a small number of patients, a condition known as ACTH deficiency may be present. This rare condition can either be inherited from one’s parents or it can be acquired during one’s lifetime. There is some controversy about the prevalence of ACTH deficiency, because its symptoms (loss of weight or appetite, vomiting, nausea, low blood pressure, and general physical weakness) are so generic that there may be many cases of ACTH deficiency that either go undiagnosed or are misdiagnosed as other ailments. There is no definitive understanding of what causes ACTH deficiency to develop, but scientists have begun to explore the genetic underpinnings that may be at work. One form of ACTH deficiency that is present at birth is caused by chromosomal defects that impair the functioning of the pituitary gland where ACTH is produced. Some ACTH deficiencies are treatable through the use of synthetically manufactured ACTH to supplement that which the body is unable to produce on its own, while other ACTH deficiencies can be more problematic to overcome. There is cause for hope that as more is learned about the human genome, additional information may become available that will help to identify the root causes of ACTH deficiency, as well as some potential therapies.

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