Summary
Cosyntropin is an FDA approved synthetic fragment of ACTH, the pituitary hormone that tells the adrenal glands to make cortisol, used as a single 250 mcg injection to test whether the adrenal glands can produce cortisol; a stimulated cortisol below about 18 mcg per dL (500 nmol per L) supports adrenal insufficiency (adrenal glands that make too little cortisol). It is a diagnostic agent given in clinics and hospitals, not a treatment, and it has been a generic drug since the 1970s. Because it stimulates cortisol release it is prohibited in sport under WADA section S2, the anti-doping class for peptide hormones.
What is Cosyntropin?
Cosyntropin is a synthetic 24 amino acid N-terminal fragment of adrenocorticotropic hormone (ACTH), melanocortin 2 receptor agonist. It is also known as Cortrosyn, tetracosactide, tetracosactrin, Synacthen, ACTH 1-24, synthetic ACTH.
How does it work?
Cosyntropin contains the first 24 amino acids of ACTH, which carry the full biological activity of the 39 amino acid native hormone. It binds the melanocortin 2 receptor on adrenal cortex cells and stimulates synthesis and release of cortisol (and to a lesser extent aldosterone and adrenal androgens) within minutes. A healthy adrenal gland roughly doubles cortisol output within 30 to 60 minutes; an atrophied or destroyed gland cannot.
| Cluster | Other peptides |
|---|---|
| Routes | Intravenous or intramuscular single injection (diagnostic); Intravenous infusion over 4 to 8 hours (prolonged test) |
| Conditions studied | None recorded |
| Record | v3, draft, verified Sep 23, 2026 |
What does the evidence say about Cosyntropin?
The cosyntropin stimulation test is the standard confirmatory test for primary adrenal insufficiency in the Endocrine Society guideline, based on decades of diagnostic accuracy studies rather than randomized trials. A 2016 systematic review and meta-analysis of 30 studies found the standard 250 mcg test performs well for primary adrenal insufficiency but has limited sensitivity (about 64%) for secondary adrenal insufficiency, where the adrenal glands may still respond to a supraphysiologic dose. There is no treatment claim to grade; the evidence grade reflects diagnostic accuracy cohorts.
| Evidence type | Indexed studies | Participants (human) |
|---|---|---|
| Human randomized trials | 0 | n/a |
| Human observational studies | 2 | n/a |
| Animal studies | 0 | n/a |
| All indexed studies | 2 | n/a |
Human evidence
Ospina 2016 (systematic review, 30 diagnostic accuracy studies): for secondary adrenal insufficiency the standard dose test had pooled sensitivity of about 64% and the 1 mcg low dose test about 92%, with similar specificity; both tests reliably identify primary adrenal insufficiency. The Endocrine Society 2016 guideline recommends the 250 mcg test as the gold standard confirmatory test with a peak cortisol cutoff below 500 nmol per L (18 mcg per dL), noting that the cutoff depends on the assay used. A 2021 Lancet review summarizes the same diagnostic approach.
Animal evidence
Animal studies established that the 1 to 24 fragment retains the full steroidogenic activity of ACTH. No animal disease model is relevant to its diagnostic use.
Key studies
| Study | Design and population | Outcome | Grade |
|---|---|---|---|
| ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis2016 PMID 26649617 | Systematic review and meta-analysis of diagnostic accuracy studies (30 studies)Patients evaluated for primary or secondary adrenal insufficiency with standard dose (250 mcg) or low dose (1 mcg) cosyntropin tests | Standard dose test sensitivity about 64% and low dose about 92% for secondary adrenal insufficiency with similar specificity; both tests perform well in primary adrenal insufficiency | Evidence: Human observational evidence |
| Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline2016 PMID 26760044 | Clinical practice guideline based on systematic evidence reviewPatients with suspected or confirmed primary adrenal insufficiency | Recommends the 250 mcg cosyntropin test as the confirmatory test, with peak cortisol under 500 nmol per L (18 mcg per dL) at 30 or 60 minutes indicating adrenal insufficiency, assay dependent | Evidence: Human observational evidence |
Is Cosyntropin legal in the United States?
FDA and compounding status
FDA approved diagnostic drug (Cortrosyn, approved 1970; generics available). It is a diagnostic agent, not a therapy, so there is no compounding or telehealth market and it is not on any 503A bulks list. Not sold as a research chemical for human use in any meaningful volume.
WADA status
WADA prohibited. Athletes subject to anti-doping testing should treat this as prohibited at all times unless the current prohibited list says otherwise.
Regulatory timeline
No regulatory events recorded.
Cosyntropin stimulation test: dose on the FDA label
Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.
FDA label (Cortrosyn, DailyMed; diagnostic use only): adults, 0.25 mg by intravenous or intramuscular injection; pediatric patients, 0.125 mg from birth to under 2 years and 0.25 mg from 2 to 17 years. Serum cortisol is drawn at baseline and exactly 30 and 60 minutes after the injection. The label advises stopping glucocorticoids and spironolactone on the test day (longer for long acting glucocorticoids) and stopping estrogen containing drugs 4 to 6 weeks before testing, because they distort cortisol results.
Routes reported
| # | Route |
|---|---|
| 1 | Intravenous or intramuscular single injection (diagnostic) |
| 2 | Intravenous infusion over 4 to 8 hours (prolonged test) |
What are the side effects and interactions of Cosyntropin?
Side effects
| # | Reported side effect |
|---|---|
| 1 | Rare hypersensitivity reactions including anaphylaxis, more likely in patients with prior ACTH allergy |
| 2 | Flushing, bradycardia, tachycardia, or hypertension reported rarely |
| 3 | Peripheral edema and rash reported rarely |
| 4 | Transient rise in cortisol is the intended effect, not an adverse one |
Interactions
| # | Interaction |
|---|---|
| 1 | Glucocorticoids (hydrocortisone, prednisone, dexamethasone) and other steroids alter baseline and stimulated cortisol measurement; the label and guideline advise timing or withholding them before the test |
| 2 | Oral estrogens raise cortisol binding globulin and total cortisol, which can produce a falsely reassuring result |
| 3 | Spironolactone may interfere with cortisol assays |
Contraindications
| # | Contraindication |
|---|---|
| 1 | History of hypersensitivity to cosyntropin or ACTH |
| 2 | Not for use as a treatment (the therapeutic ACTH products are separate) |
How do people access Cosyntropin legally?
Typical cost: One vial per test, usually billed as part of an office or hospital diagnostic procedure rather than dispensed. Cash prices for a generic 0.25 mg vial run in the low hundreds of USD.
Verified access options
Step 1
Administered by a clinician in an endocrinology clinic, hospital, or lab as part of an ACTH stimulation test.
Step 2
Not dispensed to patients and not available through compounding pharmacies or telehealth.
Access paths are verified against public regulatory records and prescriber licensing. We never list unlicensed vendors.
Frequently asked questions
What is cosyntropin used for?
It is a diagnostic test agent. A single 250 mcg injection is given and cortisol is measured 30 and 60 minutes later; if the adrenal glands cannot raise cortisol above about 18 mcg per dL (500 nmol per L, assay dependent), adrenal insufficiency (adrenal glands that make too little cortisol) is likely. It is the confirmatory test recommended by the Endocrine Society for primary adrenal insufficiency (Addison disease, where the adrenal glands themselves fail). [2] [4]
Is cosyntropin FDA approved?
Yes. Cortrosyn was approved in 1970 as a diagnostic agent for adrenocortical insufficiency and generic cosyntropin has been available for decades. It is not approved or used as a treatment; therapeutic ACTH products for conditions like infantile spasms are different drugs. [4]
How accurate is the cosyntropin stimulation test?
Very good for primary adrenal insufficiency, where the adrenal glands themselves have failed. For secondary adrenal insufficiency (pituitary causes), a 2016 meta-analysis of 30 studies found the standard 250 mcg test misses about a third of cases (sensitivity around 64%) because partly atrophied adrenals can still respond to a large ACTH dose; the 1 mcg low dose test was more sensitive (about 92%). Cutoffs also depend on the cortisol assay used. [1] [2]
What are the side effects of cosyntropin?
Very few. Because it is a single diagnostic dose, the main risk is a rare allergic reaction, including anaphylaxis, which is more likely in people previously exposed to natural ACTH. Flushing, changes in heart rate, or blood pressure and rash have been reported rarely. [4]
How is the cosyntropin stimulation test done, and what is the dose?
Blood is drawn for baseline cortisol, then cosyntropin is injected into a vein or muscle (0.25 mg for adults and children 2 to 17, 0.125 mg under age 2, per the label), and cortisol is drawn again exactly 30 and 60 minutes later. The label says to stop glucocorticoids and spironolactone on the test day and estrogen containing drugs 4 to 6 weeks before, because they distort cortisol readings. Guidelines note that dexamethasone does not cross react with cortisol assays if steroid cover is needed. [2] [4]
How much does a cosyntropin test cost?
The drug itself is a generic vial costing in the low hundreds of USD, and the full test adds clinic time and two or three cortisol assays. It is normally billed to insurance as a diagnostic procedure rather than sold to the patient. [4]
Is cosyntropin (tetracosactide) banned by WADA?
Yes. Corticotrophins and their releasing factors, with tetracosactide named as an example, are prohibited at all times under section S2 of the WADA Prohibited List because they stimulate cortisol release. An athlete who needs a diagnostic ACTH stimulation test should obtain a therapeutic use exemption or document the medical procedure with their anti-doping organization in advance. [5]
Cosyntropin vs ACTH gel: what is the difference?
Cosyntropin is the synthetic 24 amino acid fragment used once as a diagnostic test. Repository corticotropin gel is the full 39 amino acid natural hormone formulated for repeated therapeutic injection in conditions like infantile spasms and multiple sclerosis flares, at a very different cost and risk profile. They should not be confused, and cosyntropin is not a substitute for therapeutic ACTH. [3] [4]
Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.
Sources
Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.
- [1]Ospina NS et al. ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab 2016PubMed 26649617, 2016
- [2]Bornstein SR et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016PubMed 26760044, 2016
- [3]Husebye ES, Pearce SH, Krone NP, Kampe O. Adrenal insufficiency. Lancet 2021PubMed 33484633, 2021
- [4]FDA prescribing information for Cortrosyn (cosyntropin) for injection, via DailyMedFDA, 2025
- [5]WADA Prohibited List, section S2 peptide hormones, growth factors, related substances and mimetics (corticotrophins and their releasing factors)WADA, 2026
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<a href="https://peptideagent.ai/peptides/cosyntropin">Cosyntropin: evidence, legality, and access</a>, PeptideAgent, updated September 23, 2026.