Synthetic ACTH · adrenal diagnostics
Cosyntropin is a synthetic copy of the first 24 of the 39 amino acids of ACTH, the pituitary hormone that drives cortisol production. In the US it is a diagnostic agent, not a treatment: clinicians inject it to see whether the adrenal glands respond normally1.
The hormonal activity of ACTH sits in the front end of the molecule; the first 20 amino acids are the minimum needed for full activity, so the 24-residue fragment stimulates the adrenal cortex much like the natural hormone1. The short ACTH stimulation test compares blood cortisol drawn just before the injection with cortisol drawn shortly afterwards. An adrenal cortex that cannot respond leaves the later reading low, the pattern that points to adrenal insufficiency, while a normal gland lifts it well above the starting level. Results can be distorted by medicines and conditions that change cortisol or its carrier protein, including glucocorticoids, spironolactone and estrogen, so these are paused or taken into account. The label notes that the cutoff for a normal response depends on the cortisol assay used1.
Cosyntropin's evidence is about diagnostic accuracy in people rather than treatment outcomes. The Endocrine Society's guideline on primary adrenal insufficiency recommends the short corticotropin test as the "gold standard" for establishing the diagnosis, with morning ACTH and cortisol levels as a first screen when the test cannot be done3.
A patient-level meta-analysis of 13 studies (679 people suspected of hypothalamic-pituitary-adrenal insufficiency) compared the standard test with a low-dose version. The low-dose test discriminated better (area under the curve 0.92 versus 0.79), although the authors noted that it has technical limitations2. In the US, cosyntropin has no approved use beyond this testing1.
Approved by the FDA as Cortrosyn, with generic cosyntropin also available, as a diagnostic agent used alongside other tests to screen adults and children for adrenocortical insufficiency1.
Because it is given for a one-time test, the label lists only reactions reported after approval, without frequencies: hypersensitivity reactions including anaphylaxis, slow or fast heart rate, high blood pressure, swelling in the limbs and rash. People with a past allergic reaction to cosyntropin or its ingredients should not receive it. Medicines that alter cortisol or its binding protein, such as glucocorticoids, spironolactone and estrogen, can make the result misleading1.
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