Cosyntropin

Cosyntropin is a synthetic peptide that contains the first 24 amino acids of the 39-amino acid naturally occurring adrenocorticotropic hormone (ACTH). This N-terminal fragment retains full biological activity for stimulating the adrenal cortex to produce cortisol, as the first 24 amino acids contain the entire active binding region of native ACTH. The shorter peptide has the advantage of being less immunogenic than full-length ACTH, making it better suited for diagnostic use.

Cosyntropin is primarily used in the ACTH stimulation test (also called the cosyntropin stimulation test or Synacthen test), which is the gold standard diagnostic procedure for evaluating adrenal insufficiency. In this test, a standard dose of cosyntropin (250 mcg) is administered intravenously or intramuscularly, and serum cortisol levels are measured at baseline and at 30 and/or 60 minutes post-injection. A normal response is a cortisol level exceeding 18-20 mcg/dL (500-550 nmol/L) at 30 or 60 minutes, indicating adequate adrenal reserve.

The test is used to diagnose both primary adrenal insufficiency (Addison's disease, where the adrenal glands fail to respond to ACTH) and secondary adrenal insufficiency (where chronic ACTH deficiency leads to adrenal atrophy). In primary adrenal insufficiency, cortisol fails to rise after cosyntropin stimulation. In secondary adrenal insufficiency, the response is blunted because the adrenal glands have atrophied from prolonged ACTH deficiency, though mild or early secondary insufficiency may show a normal response to the standard 250 mcg dose.

A low-dose cosyntropin test (1 mcg) has been advocated by some endocrinologists as more sensitive for detecting mild or early secondary adrenal insufficiency, as the standard 250 mcg dose represents a supraphysiological stimulus that may overcome mild adrenal atrophy. However, the low-dose test has not been standardized across laboratories and is not universally adopted.