What Is ACTH (Adrenocorticotropic Hormone)? - Definition, Function & Deficiency

Instructor: Jason Lulejian

Jason has taught medicine and has a Medical Degree from Western University of Health Sciences

Does the term ACTH confuse you? Do the complex regulatory mechanisms in the adrenal system give you a never ending headache? If so, this lesson will demystify ACTH; it's function, role, and place in the endocrine system and human disease.

What Is ACTH?

A patient goes to see her doctor and says that she has lost a lot of weight and all of the sudden has a great tan. She is concerned because her eating habits haven't changed and she hasn't been spending any time in the sun. Her doctor tells her he thinks that she is suffering from a disease related to ACTH. But, what is ACTH?

ACTH stands for Adrenocorticotropic hormone, which can be a mouthful to many people. To break it down further, ACTH is an adrenal hormone (adreno) that acts on the adrenal cortex (cortical) in a regulating fashion (tropic). The hormone itself is made in the pituitary gland, namely the anterior portion of it. ACTH is composed of 39 amino acids, making a long polypeptide chain, with the first 13 of them being related to Alpha-Melanocyte-stimulating hormones (which will become relevant in later sections). The relationship between where it is made (Pituitary gland) and where it acts (Adrenal Cortex) create an axis, known as the hypothalamic-pituitary- adrenal axis.

The reason the hypothalamus is involved in this axis is that ACTH release is stimulated by corticotropin-releasing hormone. This hormone is secreted by the hypothalamus in response to neurological signals from the body.

A Healthy System: Role and Function

The role of ACTH in a healthy adrenal system is multifaceted. Primarily, ACTH acts on the adrenal cortex causing the release of Corticosteroids such as Cortisol. Cortisol is very similar to the over-the-counter medicine people buy to put on irritated skin to lower inflammation (hydrocortisone). These corticosteroids are primarily what one would call stress hormones.

We can think of it in terms of stress at work. When your mind and body are stressed by an angry boss, for example, the body releases cortisone to help bolster fuel reserves and maintain homeostasis (i.e. blood pressure and blood sugar). The ideal is that eventually the stress goes away and the body is supposed to decrease its production of cortisol.

ACTH plays a role in helping to regulate the amount of cortisol in the bloodstream relative to how much is being produced. ACTH levels generally decrease with increasing amounts of cortisol, so that there is a way of ''capping'' the amount. Conversely, when the levels of cortisol are too low, ACTH will rise in order to stimulate the adrenal glands to secrete more cortisone to balance the amount of both in the body. This is referred to as negative feedback, which is a common mechanism in the body to regulate levels of hormones and activities of hormone producing organs.

A Diseased System: Role and Function

Depending on the disease, ACTH can either increase or decrease and both can be found by testing. Let us discuss what happens in either case.

Excess ACTH

Cushing

The excess of ACTH causes a syndrome called Cushing's disease where the body begins to store excess fat, increase blood sugar concentration and blood pressure. This particular disease can be caused by both issues at the level of the adrenal system, but can be primarily caused by ACTH being overproduced by a pituitary tumor.

The rationale for checking cortisol levels is that ACTH levels in the blood are variable and it's only realistic to look at responses (i.e. does the level change in response?) than to look for a normal level. Dexamethasone is a related compound to cortisol, which can activate the negative feedback system to see if it is functioning properly.

Cortisol levels can be too low (from dysfunction of the adrenal cortex), hence creating very high levels of ACTH, which is primarily manifested in the disease known as Addison's disease. People that have this disease generally have difficulty controlling their blood pressure, sugars, and have a distinctive tanned skin. The reason why patients have difficulties with blood sugar and blood pressure is that, as mentioned above, cortisol is a critical regulator of those two systems.

However, the tanned skin can come through the overproduction of the Alpha-Melanocyte-stimulating hormone, which is a byproduct of the high levels of ACTH (ACTH's first 13 amino acids). One very famous sufferer of Addison's disease was president John F. Kennedy, who was well known for his lovely tanned skin. This tanned skin was primarily a symptom of his underlying disease.

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