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Cosyntropin: The First 24 Residues of ACTH, Used to Test the Adrenal Glands

Cosyntropin (Cortrosyn) is a synthetic peptide made of the first 24 of ACTH's 39 amino acids. It is not a treatment: it is injected once, and blood cortisol is measured 30 and 60 minutes later to screen for adrenal insufficiency. The label sets the cut-off and lists the medicines that can make the result wrong.

FDA-approved (since 1970)Diagnostic agent onlySingle injection, intravenous or intramuscular

Caroline S · Published 2026-10-05

Length

24 amino acids in an open chain — the first 24 of ACTH's 39; molecular weight 2,934 g/mol, formula C136H210N40O31S (Cortrosyn label)

Sequence

SYSMEHFRWGKPVGKKRRPVKVYP — identical to residues 1–24 of human ACTH (ACTH sequence: UniProt P01189)

Origin

Fully synthetic. Cortrosyn's application (NDA 016750) dates to 1970-04-22 in Drugs@FDA and is held today by Amphastar

Last reviewed

2026-10-05

What is it good for?

Nothing as a treatment. It is a diagnostic agent: it stands in for ACTH in the stimulation test, which asks whether the adrenal glands can raise cortisol on command. A low rise suggests adrenal insufficiency; the label says the test is used in combination with other tests.

Illustration: A molecular model of a 24-residue peptide on a white lab bench with a copper-accented beaker.
Illustration

What it is

Cosyntropin is the front 24 amino acids of ACTH, made synthetically. Natural ACTH, the pituitary's cortisol signal, is 39 residues long (see the ACTH entry); cosyntropin stops at residue 24:

SYSMEHFRWGKPVGKKRRPVKVYP

The Cortrosyn label gives its formula as C136H210N40O31S and its weight as 2,934 g/mol. Each single-dose vial holds 0.25 mg of powder with mannitol. Outside the US the same molecule is known as tetracosactide, sold in Europe as Synacthen (PubChem synonyms, 2026-10-05).

Why only 24 residues

The label explains why the tail can go. All of ACTH's adrenal-stimulating activity sits at the front: residues 1–20 are the shortest sequence with full activity, and cutting from 20 to 19 loses 70% of potency. Most of its ability to provoke antibodies sits at the back, residues 22–39. A 1–24 peptide therefore keeps the biology and drops most of the immune target — the property the label singles out "in view of the known antigenicity of natural ACTH."

On potency, the label states that 0.25 mg stimulates the adrenal cortex maximally and to the same extent as 25 units of natural ACTH.

The test, as the label describes it

Cosyntropin has one approved job: standing in for ACTH in the stimulation test, which asks whether the adrenal glands can raise cortisol when told to.

Step (Cortrosyn label) Detail
Dose 0.25 mg, ages 2–17 and adults; 0.125 mg, birth to under 2 years
Route Intravenous or intramuscular
Samples Cortisol at baseline, then exactly 30 and 60 minutes after
Reading Stimulated cortisol below 18 mcg/dL at 30 or 60 minutes is "suggestive of adrenocortical insufficiency"
Caveat Cut-offs "may vary according to the assay used"

The label calls the test a screen, used in combination with other diagnostic tests. It does not, on its own, say which kind of adrenal insufficiency is present or what causes it; that is the ordering clinician's work.

What skews the result

The label's main warning is not about harm but about a wrong answer:

  • Glucocorticoids and spironolactone can falsely raise measured cortisol. The label sets stopping them on the day of the test, and longer for long-acting glucocorticoids.
  • Oestrogen-containing drugs raise cortisol-binding globulin, which raises total cortisol. The label sets stopping them four to six weeks before.
  • Any condition that raises or lowers that binding globulin moves total cortisol with it.

Safety

Because it is given once, the label's adverse-reaction list comes from postmarketing reports rather than trials: anaphylaxis, slow or fast heart rate, high blood pressure, peripheral swelling and rash. The warnings section adds monitoring for hypersensitivity.

Where it stands

Drugs@FDA lists Cortrosyn (Amphastar, NDA 016750, 1970-04-22) and a Sandoz generic (ANDA 202147, 2012-06-29) as prescription products; a Sandoz new-drug application (2008) and another generic (2009) are discontinued (openFDA, 2026-10-05). PubMed indexes 2,230 records for cosyntropin and 133 tagged as randomised controlled trials (2026-10-05) — a count that mostly reflects its use as a measuring tool inside trials of other treatments, not trials of cosyntropin itself.

The full hormone, its precursor and the porcine gels sold as treatments are in the ACTH entry. ACTH is cut from the same precursor as the melanocyte-stimulating hormones that melanotan-1 and melanotan-2 were modelled on.

What the research shows

Screening for adrenocortical insufficiency

FDA-approved indication (diagnostic only), in adults and children, in combination with other diagnostic tests (Cortrosyn label)

Matches natural ACTH's effect on the adrenal cortex

Label: 0.25 mg stimulates the adrenal cortex maximally and to the same extent as 25 units of natural ACTH

Bars show how much of the evidence is in humans, not how well anything works.

Where it stands

United States

Approved as a diagnostic. Drugs@FDA lists Cortrosyn (Amphastar, NDA 016750, 1970-04-22) and a Sandoz generic (ANDA 202147, 2012-06-29) as prescription products; a Sandoz NDA (022028, 2008) and another generic (ANDA 090574, 2009) are discontinued (openFDA, 2026-10-05).

How it is given

A single intravenous or intramuscular injection, with blood drawn for cortisol at baseline and exactly 30 and 60 minutes after (label).

Published record

PubMed indexes 2,230 records for cosyntropin, 133 tagged as randomised controlled trials (2026-10-05) — most use it as a test inside studies of other treatments.

Frequently asked questions

What is cosyntropin?

A synthetic peptide matching the first 24 amino acids of ACTH, the pituitary hormone that drives cortisol. It is used only as a test agent, not a treatment. Outside the US the same molecule is called tetracosactide.

Is cosyntropin the same as ACTH?

It is the front 24 residues of ACTH's 39. The label says that portion carries the full adrenal-stimulating activity, and that 0.25 mg matches 25 units of natural ACTH. The missing tail carries most of ACTH's ability to provoke antibodies.

How is the cosyntropin stimulation test done?

On the label: a blood sample for cortisol, a single injection of cosyntropin into a vein or muscle, then cortisol samples at exactly 30 and 60 minutes. The label describes a result below 18 mcg/dL as suggestive of adrenal insufficiency, with the caveat that cut-offs vary by assay.

What can make the test result wrong?

The label names glucocorticoids and spironolactone, which can falsely raise cortisol, and oestrogen-containing drugs, which raise the protein that carries cortisol. It gives stopping times for each; which medicines to stop, and when, is decided by the clinician ordering the test.

What does a low result mean?

The label calls it suggestive, not diagnostic, of adrenal insufficiency, and says the test is used with other tests. A result is interpreted by the clinician who ordered it.

Does cosyntropin have side effects?

The label lists anaphylaxis and other allergic reactions, slow or fast heart rate, high blood pressure, swelling and rash, reported after marketing. It is given once, under supervision.