Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
The diagnostic peptide: 24 residues of ACTH that ask the adrenal gland whether it can still respond.
Also known as: tetracosactide · ACTH(1-24) · Cortrosyn / Synacthen (brands) · tetracosapeptide
Part of the Foundational & therapeutic peptides cluster
Overview
Cosyntropin (tetracosactide) is a synthetic 24-residue peptide identical to the fully active N-terminal portion of ACTH. It retains full melanocortin-2 receptor activity and stimulates the adrenal cortex to secrete cortisol, which is why it has been used since 1970 as the standard stimulation test for diagnosing adrenal insufficiency and, more recently, during adrenal vein sampling in primary aldosteronism.
Source & context
Biological / chemical source: Synthetic peptide comprising the fully active N-terminal 24 residues of corticotropin (ACTH)
Primary research or clinical context: Approved (FDA 1970) as a diagnostic agent for adrenal insufficiency (cosyntropin stimulation test)
What cosyntropin is
Cosyntropin, known outside North America as tetracosactide, is a synthetic peptide forming the fully active N-terminal portion of corticotropin (ACTH). Like the endogenous hormone, it stimulates the adrenal cortex to produce and secrete adrenocortical hormones (IUPHAR ligand 6965). The IUPHAR record gives FDA approval in 1970 and its primary use as a diagnostic for adrenal insufficiency. Its 24-residue sequence, S-Y-S-M-E-H-F-R-W-G-K-P-V-G-K-K-R-R-P-V-K-V-Y-P, is the segment of ACTH that carries receptor activity; the remaining 15 residues of the 39-residue hormone are dispensable for adrenal stimulation.
Mechanism
The peptide retains full melanocortin-2 receptor activity compared with naturally occurring corticotropin in its ability to stimulate secretion of adrenocortical hormones (IUPHAR mechanism record). MC2R is expressed almost exclusively on adrenocortical cells, so the response to a cosyntropin injection — a rise in serum cortisol — is a direct read-out of whether the adrenal gland can respond to ACTH. A blunted rise points to primary adrenal insufficiency or to adrenal atrophy from long-standing ACTH deficiency.
The stimulation test
The cosyntropin stimulation test is the standard dynamic test for adrenal insufficiency, and its interpretation is being refined: one registered study is updating diagnostic cortisol cut-offs for the test (NCT05149638), and another screens for residual adrenal steroid secretion in autoimmune Addison's disease (NCT03793114). The test is also used in immune-checkpoint-inhibitor-induced adrenal insufficiency, an increasingly recognised complication of cancer immunotherapy (Rai & Go, Cureus 2020), and in the work-up of congenital adrenal hyperplasia (El-Maouche et al., Lancet 2017).
Adrenal vein sampling
A second major use is during adrenal vein sampling (AVS) for subtyping primary aldosteronism, where cosyntropin infusion raises cortisol output from both adrenals and improves confirmation that the catheter is correctly placed. The international AVIS-2 registry of 1,625 procedures examined how selectivity and lateralisation cut-offs perform with and without stimulation (Rossitto et al., Journal of Clinical Endocrinology & Metabolism 2020); later studies used a selectivity index of at least 3 bilaterally after cosyntropin stimulation to define success (Grundy et al., Hypertension 2025) and examined partially successful sampling before and after stimulation (Vibhatavata et al., Hypertension 2026). A 2026 study measured 33 urinary steroid metabolites before and after 250 μg intravenous cosyntropin in primary aldosteronism with and without cortisol co-secretion (Araujo-Castro et al., Endocrine Practice 2026).
Status and identifiers
Cosyntropin is an approved diagnostic medicine (Cortrosyn in North America; Synacthen elsewhere). ClinicalTrials.gov lists 41 registered studies naming it as of September 2026, nearly all using it as a test agent rather than a treatment. The IUPHAR record cross-links ChEMBL (CHEMBL2103784), DrugBank (DB01284) and PubChem (CID 16129617).
Related peptides on this site
Cosyntropin is the pharmaceutical fragment of ACTH; the α-MSH-derived tripeptide KPV and the melanotan analogues act on other melanocortin receptors (MC1R, MC4R) and are covered on their own profiles. This page is educational and is not guidance on performing or interpreting any test.
Sequence
One-letter sequence commonly cited for Cosyntropin (educational; isoforms and modifications may differ):
SYSMEHFRWGKPVGKKRRPVKVYP
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Residues 1–24 of human ACTH (the fully active N-terminal segment)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C136H210N40O31S
- Average reference mass
- ≈ 2,933.4
- Receptors
- Melanocortin-2 receptor (MC2R) on adrenocortical cells — full agonist, equal in potency to native corticotropin
- Backbone
- Residues 1–24 of human ACTH (the fully active N-terminal segment)
- Status
- Approved: FDA (1970) as a diagnostic agent
- PubChem CID: 16129617
- IUPHAR ligand: 6965
- ChEMBL: CHEMBL2103784
- DrugBank: DB01284
- CAS RN: 16960-16-0
- UNII: 72YY86EA29
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 41 registered studies with “Cosyntropin” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06190158 | Subclinical Primary Aldosteronism in Diabetes At-Risk for Kidney Disease | Early phase 1 | active not recruiting | 2026-08-13 |
| NCT03793114 | Screening and Stimulation Testing for Residual Secretion of Adrenal Steroid Hormones in Autoimmune Addison's D | Not applicable | active not recruiting | 2026-05-08 |
| NCT05149638 | Updated Diagnostic Cortisol Values for Adrenal Insufficiency | Not applicable | recruiting | 2026-02-19 |
| NCT04546126 | Positron Emission Tomography (PET) Imaging of Cholesterol Trafficking: Clinical Evaluation of [18F]FNP-59 in N | Early phase 1 | recruiting | 2025-12-05 |
| NCT02339506 | Stress and the Nervous System | Not applicable | completed | 2025-12-03 |
| NCT04037605 | Hormonal Mechanisms of Sleep Restriction - Axis Study in Older Men and Postmenopausal Women | Early phase 1 | active not recruiting | 2025-09-11 |
Cosyntropin — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Residues 1–24 of human ACTH (the fully active N-terminal segment)Average reference mass: 2,933.4 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 6965 and PubChem CID 16129617.
- TrialsClinicalTrials.gov snapshot added: 41 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Cosyntropin
What is Cosyntropin?+
Cosyntropin (tetracosactide) is a synthetic 24-residue peptide identical to the fully active N-terminal portion of ACTH. It retains full melanocortin-2 receptor activity and stimulates the adrenal cortex to secrete cortisol, which is why it has been used since 1970 as the standard stimulation test for diagnosing adrenal insufficiency and, more recently, during adrenal vein sampling in primary aldosteronism.
What Canadian product status is recorded for Cosyntropin?+
Canadian product status for Cosyntropin has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Cosyntropin?+
Cosyntropin is commonly described as approximately 24 amino acids (Synthetic ACTH fragment).
What is cosyntropin?+
A synthetic 24-residue peptide identical to the active N-terminal segment of ACTH (tetracosactide). It stimulates the adrenal cortex and has been an FDA-approved diagnostic agent since 1970.
What is the cosyntropin stimulation test?+
A test of adrenal function: cosyntropin is injected and serum cortisol is measured. A blunted cortisol rise indicates adrenal insufficiency.
Is cosyntropin the same as ACTH?+
It is the first 24 of ACTH's 39 residues — the part that carries full melanocortin-2 receptor activity.
Why is cosyntropin used in adrenal vein sampling?+
Stimulating both adrenals with cosyntropin raises cortisol output and helps confirm correct catheter placement when subtyping primary aldosteronism.
Related peptides
References & further reading
- 1.Rossitto et al. (2020). Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization. Journal of Clinical Endocrinology & Metabolism
- 2.Grundy et al. (2025). Outcomes After Unilateral Adrenalectomy in Asymmetrical Bilateral Primary Aldosteronism. Hypertension
- 3.Vibhatavata et al. (2026). Partially Successful Adrenal Vein Sampling With and Without Cross-Sectional Imaging in Primary Aldosteronism Subtyping. Hypertension
- 4.Araujo-Castro et al. (2026). Impact of the Cosecretion of Cortisol on Surgical Outcomes and in the Urinary Steroid Profile in Primary Aldosteronism. Endocrine Practice
- 5.El-Maouche et al. (2017). Congenital adrenal hyperplasia. Lancet
- 6.Rai & Go (2020). Nivolumab Induced Adrenal Insufficiency: Rare Side-effect of a New Anti-cancer Therapy. Cureus
- 7.PubChem — compound summary for Tetracosactide (CID 16129617)