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ACTH (1-24)
A synthetic peptide containing the first 24 amino acids of adrenocorticotropic hormone, used as a diagnostic agent to test adrenal gland function and cortisol production capacity.
Overview
ACTH (1-24), also known as cosyntropin or tetracosactide, is a synthetic peptide comprising the first 24 amino acids of the native 39-amino acid adrenocorticotropic hormone (ACTH). This truncated form retains the full biological activity of native ACTH because the biologically active site resides within the first 24 amino acids. Cosyntropin is the most widely used diagnostic agent for evaluating adrenal insufficiency.
The cosyntropin stimulation test (ACTH stimulation test) is the gold standard for diagnosing adrenal insufficiency. In this test, 250 mcg of cosyntropin is administered intravenously or intramuscularly, and serum cortisol levels are measured at baseline and 30-60 minutes post-injection. A normal response is defined as a stimulated cortisol level of ≥ 18-20 mcg/dL (500-550 nmol/L), though some experts argue for lower thresholds with modern cortisol assays. Failure to mount an adequate cortisol response indicates adrenal insufficiency.
The standard 250 mcg dose represents a supraphysiological stimulus — it produces ACTH levels far exceeding those normally seen even during severe physiological stress. This supraphysiological dosing makes the test very sensitive for detecting primary adrenal insufficiency (Addison's disease) but potentially less sensitive for detecting mild or early secondary (pituitary-driven) adrenal insufficiency. For this reason, a low-dose cosyntropin test using 1 mcg has been proposed and studied as a more physiological stimulus that may be more sensitive for secondary adrenal insufficiency.
Cosyntropin has also been used therapeutically, particularly as Synacthen Depot (a depot formulation of tetracosactide) for treating conditions such as infantile spasms (West syndrome), multiple sclerosis relapses, and various inflammatory conditions in countries where it is available. The depot formulation provides sustained ACTH activity and endogenous cortisol production, which some clinicians prefer over exogenous corticosteroid administration.