What is true about Adrenocorticotropic Hormone (ACTH)?

From the Guidelines

The true statement about adrenocorticotropin hormone (ACTH) is that the 250-μg ACTH stimulation test is suggested for the diagnosis of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients. The use of ACTH stimulation test is a crucial diagnostic tool in assessing adrenal insufficiency, and the high-dose test is preferred due to its ease of use and comparable accuracy to the low-dose test 1, 2. The high-dose ACTH test has been found to have similar diagnostic accuracy to the low-dose test, with a likelihood ratio of a positive test of 9.1 and 5.9 for the high- and low-dose ACTH test, respectively, for adults 2. Some studies suggest that the low-dose ACTH test may be better at predicting certain outcomes, such as vasopressor dependency and mortality, but the high-dose test is generally preferred due to its practicality and accuracy 2, 3. Key points about ACTH include:

• ACTH is produced by the anterior pituitary gland and stimulates the adrenal cortex to produce and release cortisol
• ACTH plays a crucial role in the body's stress response system, known as the hypothalamic-pituitary-adrenal (HPA) axis
• Disorders involving ACTH include Cushing's syndrome (excess ACTH) and Addison's disease (insufficient adrenal response to ACTH)
• ACTH follows a diurnal rhythm, with levels typically highest in the early morning and lowest in the evening, which corresponds with the body's natural cortisol pattern. Overall, the 250-μg ACTH stimulation test is a valuable tool in diagnosing CIRCI, and its use is supported by recent guidelines and studies 1, 2, 3.

From the FDA Drug Label

Cosyntropin exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N-terminal portion of the molecule and that the 1-20 amino acid residue is the minimal sequence retaining full activity Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residues.

The adrenocorticotropic hormone (ACTH) has the following properties:

• Biologic activity: resides in the N-terminal portion of the molecule
• Minimal sequence: 1-20 amino acid residue is the minimal sequence retaining full activity
• Loss of activity: partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residues [4] [5]

From the Research

Adrenocorticotropin Hormone (ACTH) Statements

The following statements can be made about the adrenocorticotropin hormone:

• Excess secretion of ACTH by a benign monoclonal pituitary adenoma results in Cushing's disease (CD) 6
• The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol 6
• ACTH-dependent Cushing's syndrome can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary 7
• The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system that involves ACTH 7
• Secondary adrenal insufficiency can result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy, which affects ACTH secretion 7