Skip to content
approvedHormone Regulation

Cosyntropin

Also known as: Cortrosyn, Tetracosactide, Synacthen, ACTH(1-24), Tetracosactrin, Cosyntropin for Injection

Cosyntropin (Cortrosyn) is a synthetic peptide consisting of the first 24 amino acids of the 39-amino acid adrenocorticotropic hormone (ACTH). This N-terminal fragment retains full biological activity at the ACTH receptor (MC2R) and is the standard diagnostic agent for the ACTH stimulation test (cosyntropin stimulation test), which evaluates adrenal cortisol reserve. FDA-approved since the 1970s, it is the most commonly performed endocrine function test worldwide, essential for diagnosing adrenal insufficiency (Addison disease), evaluating hypothalamic-pituitary-adrenal (HPA) axis suppression from chronic glucocorticoid therapy, and assessing congenital adrenal hyperplasia.

3 cited references·5 researched benefits

Quick Answer

Cosyntropin (Cortrosyn) is a synthetic ACTH(1-24) fragment used as the standard diagnostic agent for the ACTH stimulation test. Administered as a 250 mcg IV or IM injection, it stimulates the adrenal cortex to produce cortisol, with blood drawn at 30 and 60 minutes. A cortisol response exceeding 18-20 mcg/dL rules out primary adrenal insufficiency. It is the gold standard test for diagnosing Addison disease and evaluating HPA axis function.

Key Facts

Mechanism
Cosyntropin binds to the melanocortin 2 receptor (MC2R), a Gs-coupled GPCR expressed on adrenocortical zona fasciculata and zona reticularis cells. MC2R requires the accessory protein MRAP (melanocortin receptor accessory protein) for surface expression and signaling. Receptor activation stimulates adenylyl cyclase, increasing intracellular cAMP, which activates PKA-mediated phosphorylation of StAR (steroidogenic acute regulatory protein) and cholesterol side-chain cleavage enzyme (CYP11A1), rapidly mobilizing cholesterol into the mitochondrial steroidogenic pathway. This produces a cortisol response within 30 minutes. The first 24 amino acids of ACTH contain the complete receptor binding domain; residues 25-39 primarily confer stability to the native hormone but are not required for biological activity. Cosyntropin's synthetic nature eliminates allergic reactions to animal-derived ACTH preparations.
Research Status
approved
Half-Life
~15 minutes (plasma)
Molecular Formula
C₁₃₆H₂₁₀N₄₀O₃₁S
Primary Use
Hormone Regulation
Table of Contents

Benefits

  • Gold standard diagnostic test for primary adrenal insufficiency (Addison disease) — sensitivity of 95-97% for detecting complete adrenal failurestrong
  • Evaluates HPA axis suppression from chronic glucocorticoid therapy — helps determine when it is safe to discontinue exogenous steroidsstrong
  • Screens for congenital adrenal hyperplasia — stimulated 17-hydroxyprogesterone levels identify 21-hydroxylase deficiency carriers and affected individualsstrong
  • Simple, rapid, and safe — results available within 60 minutes; can be performed in outpatient settings with minimal riskstrong
  • Therapeutic use of depot tetracosactide (Synacthen Depot) for infantile spasms and other conditions in some countries — alternative to repository corticotropinmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous or intramuscular (standard-dose ACTH stimulation test)250 mcgSingle dose; cortisol measured at 0, 30, and 60 minutesStandard high-dose test. A 30- or 60-minute cortisol >=18 mcg/dL (500 nmol/L) is considered a normal response, ruling out primary adrenal insufficiency. Some centers use a 20 mcg/dL cutoff.
Intravenous (low-dose ACTH stimulation test)1 mcgSingle dose; cortisol measured at 0, 20, and 30 minutesLow-dose test may detect partial or secondary adrenal insufficiency missed by the standard 250 mcg dose. More physiologic stimulus. Requires dilution of standard 250 mcg vial. Controversial — some experts prefer it for detecting subtle HPA axis suppression.
Intramuscular depot (Synacthen Depot, therapeutic)0.5-1 mg2-3 times per weekDepot formulation available in Europe and some other markets. Used therapeutically for infantile spasms, multiple sclerosis exacerbations, and other conditions where adrenal stimulation is desired. Not available in the US.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Mild flushing and skin warmth — the most commonly reported effect, occurring in <5% of patients and resolving within minutescommon
  • Transient tachycardia — small increase in heart rate occasionally observed after injectioncommon
  • Allergic reactions — rare hypersensitivity including urticaria and pruritus; extremely rare anaphylaxis reported in patients with pre-existing allergiesrare
  • Injection site reactions — minor pain or erythema at IV or IM injection sitecommon

Frequently Asked Questions

What does the cosyntropin stimulation test diagnose?
The cosyntropin (ACTH) stimulation test primarily diagnoses primary adrenal insufficiency (Addison disease), where the adrenal glands fail to produce adequate cortisol. A cortisol level that fails to rise above 18-20 mcg/dL at 30 or 60 minutes after 250 mcg cosyntropin indicates adrenal failure. The test also evaluates secondary adrenal insufficiency (pituitary ACTH deficiency) and HPA axis suppression from chronic glucocorticoid use, though sensitivity for these is lower with the standard 250 mcg dose — the low-dose 1 mcg test may be more sensitive for detecting partial insufficiency.
What is the difference between the standard-dose and low-dose cosyntropin test?
The standard 250 mcg dose produces supraphysiologic ACTH levels that maximally stimulate the adrenal cortex. It is excellent for detecting complete adrenal failure (primary adrenal insufficiency) but may miss partial or early secondary insufficiency because even partially atrophied adrenals can respond to such high stimulation. The 1 mcg low-dose test produces more physiologic ACTH levels and may unmask subtle adrenal insufficiency that the high-dose test misses. However, the low-dose test has practical challenges (requires careful dilution, shorter peak window) and its superiority remains debated in the literature.
How is cosyntropin different from corticotropin (ACTH)?
Cosyntropin is the synthetic first 24 amino acids of the full 39-amino acid ACTH molecule. It retains 100% of the biological activity because the MC2R binding domain is within the first 24 residues. Corticotropin (full-length ACTH, marketed as Acthar Gel) is derived from porcine pituitary or manufactured synthetically and includes all 39 amino acids. Cosyntropin is used almost exclusively as a diagnostic agent, while corticotropin (Acthar Gel) is used therapeutically for infantile spasms, MS exacerbations, and nephrotic syndrome. Cosyntropin is inexpensive (~$50-100 per vial) while Acthar Gel is extremely costly (~$40,000 per vial).
Can the cosyntropin test be done on patients taking hydrocortisone?
Hydrocortisone (cortisol) replacement must be held before the cosyntropin test because it directly cross-reacts with the cortisol immunoassay, producing falsely elevated results. The standard protocol is to hold the morning hydrocortisone dose and perform the test before the next scheduled dose, typically with at least 12-18 hours since the last dose. Dexamethasone and prednisone do not cross-react with most cortisol assays and can be substituted temporarily. Some experts recommend switching to dexamethasone for 24 hours before testing to maintain glucocorticoid coverage without assay interference.

References

  1. 1
    Rapid screening test for adrenal insufficiency using synthetic ACTH(1-24)(1969)PubMed ↗
  2. 2
    Comparison of low-dose and standard-dose cosyntropin stimulation tests in adrenal insufficiency(2010)PubMed ↗
  3. 3
    Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline(2016)PubMed ↗

Latest Research

Last updated: 2026-02-19