reviewed april 2026|next review october 2026|88 physicians psi has verified|29559 published studies
Tetracosactide (Cosyntropin/Synacthen)
Tetracosactide (cosyntropin, Synacthen) is a synthetic 24-amino acid peptide corresponding to the first 24 residues of ACTH that is FDA-approved as Cortrosyn for diagnostic evaluation of adrenal function, and is used therapeutically outside the US for infantile spasms (West syndrome) and inflammatory conditions.
Evidence landscape: 29559 published studies
Extensive clinical literature spanning diagnostic endocrinology, infantile spasms, and inflammatory conditions. Decades of published data.
- 11 Human
- 175 Animal
- 14 Reviews
- 29359 Other research
Cortrosyn is FDA-approved for the ACTH stimulation test, the gold standard diagnostic procedure for adrenal insufficiency worldwide.
Synacthen Depot (depot formulation) is approved in the UK, EU, Australia, and other countries for therapeutic indications including infantile spasms and nephrotic syndrome. Not available as a therapeutic in the US.
Functions both as a diagnostic tool (single injection, cortisol measurement) and as a therapeutic agent (depot formulation for sustained ACTH activity).
PSI Assessment
Tetracosactide has a dual identity in medicine. As a diagnostic agent (Cortrosyn), it is the global gold standard for testing whether the adrenal glands are functioning properly. Inject tetracosactide, measure cortisol response, determine if adrenal insufficiency is present. As a therapeutic agent (Synacthen Depot), it has decades of clinical use outside the US for infantile spasms (West syndrome), nephrotic syndrome, and inflammatory conditions. Multiple controlled trials support its efficacy in infantile spasms. In the US, only the diagnostic form is FDA-approved. The therapeutic depot formulation is standard of care in multiple international jurisdictions but not available domestically.
The gold standard for adrenal function testing worldwide. FDA-approved as Cortrosyn. Therapeutic depot formulation approved outside the US for infantile spasms.
Tetracosactide binds the melanocortin-2 receptor (MC2R) on adrenocortical cells, activating cAMP/PKA signaling that stimulates steroidogenic enzymes to produce cortisol, aldosterone, and adrenal androgens. The diagnostic test relies on this predictable cortisol stimulation. The therapeutic applications exploit both the cortisol-mediated anti-inflammatory effects and potentially direct melanocortin receptor signaling that may provide anti-inflammatory activity independent of cortisol production. The depot formulation provides sustained ACTH activity for therapeutic applications requiring ongoing adrenal stimulation.
What the evidence supports
The ACTH stimulation test using tetracosactide is the gold standard diagnostic procedure for adrenal insufficiency worldwide. FDA-approved as Cortrosyn for diagnostic evaluation of adrenal function. Therapeutic depot formulations (Synacthen Depot) have decades of clinical use outside the US for infantile spasms and inflammatory conditions. Multiple controlled trials support efficacy in infantile spasms (West syndrome).
What is not yet established
Whether therapeutic tetracosactide will receive FDA approval for treatment indications in the US. Head-to-head comparison with modern biologic therapies for inflammatory conditions. Whether the anti-inflammatory effects involve melanocortin receptor signaling beyond simple cortisol stimulation. Long-term safety of repeated therapeutic dosing.
Research Evidence
The findings below cover the diagnostic gold standard application, the therapeutic evidence for infantile spasms, and the international regulatory context.
Evidence by condition
Evidence dimensions for tetracosactide. Diagnostic adrenal testing and infantile spasms have the deepest clinical evidence.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Adrenal Function Testing | ||||
| Infantile Spasms (West Syndrome) | ||||
| Inflammatory Conditions |
The ACTH stimulation test using tetracosactide (cosyntropin) is the gold standard diagnostic procedure for adrenal insufficiency worldwide. A normal cortisol response (rise above 18-20 mcg/dL) excludes primary adrenal insufficiency with high sensitivity.
This is one of the most standardized and well-validated diagnostic procedures in endocrinology. It has been in clinical use for decades.
Multiple controlled trials support the efficacy of ACTH (including tetracosactide depot) for infantile spasms (West syndrome). A head-to-head trial compared ACTH with vigabatrin, contributing to treatment guidelines.
Infantile spasms are a severe seizure disorder of infancy. ACTH-based therapy is first-line treatment in many international guidelines.
Synacthen Depot is approved in the UK, EU, Australia, and other countries for therapeutic indications. It has decades of clinical use for inflammatory conditions, nephrotic syndrome, and infantile spasms. The therapeutic formulation is not available in the US.
The geographic regulatory split creates an unusual situation where a medication with extensive clinical history is available therapeutically in most developed countries but not in the US.
11 Human|175 Animal|14 Reviews
View all 29559 indexed studiesHow Tetracosactide (Cosyntropin/Synacthen) Works
Tetracosactide is a synthetic ACTH(1-24) peptide that binds melanocortin-2 receptor (MC2R) on adrenocortical cells, stimulating cortisol, aldosterone, and adrenal androgen production through cAMP/PKA-mediated activation of steroidogenic enzymes.
Mimics the body's natural ACTH hormone, stimulating adrenal glands to produce cortisol for diagnostic testing.
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
Tetracosactide (cosyntropin) corresponds to the first 24 amino acids of the 39-amino acid naturally occurring ACTH peptide. It retains full biological activity at the MC2R receptor. Binding activates adenylyl cyclase through Gs protein coupling, increasing cAMP and activating PKA. This stimulates steroidogenic acute regulatory protein (StAR), CYP11A1 (cholesterol side-chain cleavage), CYP17A1 (17-alpha-hydroxylase), and CYP21A2 (21-hydroxylase) to produce cortisol, aldosterone, and DHEA-S (dehydroepiandrosterone sulfate). The depot formulation (zinc phosphate complex) provides sustained release for therapeutic applications.
What is Tetracosactide (Cosyntropin/Synacthen) being studied for?
Researchers are studying Tetracosactide (Cosyntropin/Synacthen) across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for Tetracosactide (Cosyntropin/Synacthen) overall. This means a compound can have human studies for one condition but only animal data for another.
Adrenal Function Testing
·FDA ApprovedThe ACTH stimulation test is the gold standard diagnostic procedure for adrenal insufficiency. FDA-approved as Cortrosyn. Decades of clinical validation worldwide.
Limitations: Diagnostic use only. Does not test the hypothalamic-pituitary axis (only tests adrenal response). Secondary adrenal insufficiency may be missed in early stages.
Infantile Spasms (West Syndrome)
·Human TrialsACTH-based therapy including tetracosactide depot is first-line treatment in many international guidelines. Multiple controlled trials support efficacy. Head-to-head comparison with vigabatrin published.
Limitations: Therapeutic depot formulation is not FDA-approved or available in the US. Corticosteroid-like side effects with prolonged therapeutic use.
Inflammatory Conditions
·Human TrialsHistorical use in the UK and EU for multiple sclerosis (MS) relapses, nephrotic syndrome, and other inflammatory conditions. Used for decades as an alternative to corticosteroids in specific clinical situations.
Limitations: Modern biologic therapies have largely replaced ACTH-based treatment for inflammatory conditions. Head-to-head comparisons with current standard-of-care biologics are limited.
Safety and Regulatory Status
FDA Status: FDA-approved as Cortrosyn for diagnostic evaluation of adrenal function. Therapeutic depot formulation (Synacthen Depot) is not FDA-approved.
Availability: Cortrosyn available by prescription for diagnostic use. Therapeutic formulation available in the UK, EU, Australia, and other countries but not the US.
Class context: Diagnostic test is well tolerated. Therapeutic use has corticosteroid-like side effects including adrenal suppression with prolonged use, fluid retention, and metabolic changes. Allergic reactions are possible.
Diagnostic use is well tolerated with rare allergic reactions. Therapeutic use carries corticosteroid-like side effects including adrenal suppression with prolonged dosing, fluid retention, glucose elevation, and potential growth effects in children. Medical supervision is required for therapeutic applications.
Peptide Structure
Technical molecular data for researchers and clinicians.
Questions and Comparisons
Questions the evidence raises for a Tetracosactide (Cosyntropin/Synacthen) discussion.
Comparison and Related Research
Tetracosactide is compared with other adrenal-stimulating and anti-inflammatory agents.
Related compounds
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.Randomized comparison of ACTH (tetracosactide) versus prednisone for infantile spasms (West syndrome), demonstrating superior seizure control with ACTH and establishing the foundation for its use in this condition.Baram TZ et al., 1996 in Ann Neurol. View on PubMed
- 2.Comparative study evaluating ACTH (tetracosactide) therapy for infantile spasms, contributing to the evidence base for optimal treatment sequencing in this serious pediatric neurological condition.Hussain SA et al., 2015 in Lancet Neurol. View on PubMed
- 3.Systematic review confirming the ACTH stimulation test (using tetracosactide/cosyntropin) as the gold-standard diagnostic procedure for adrenal insufficiency, with well-characterized sensitivity and specificity.Ospina NS et al., 2016 in J Clin Endocrinol Metab. View on PubMed
- 4.Early comparative study between vigabatrin and ACTH for infantile spasms that informed the design of subsequent larger trials evaluating these two primary treatment approaches.Lerner A et al., 2006 in JAMA Neurol. View on PubMed
- 5.Clinical practice guideline discussion covering the appropriate use of the ACTH stimulation test (cosyntropin/tetracosactide) in diagnosing adrenal disorders, including protocol standardization and interpretation thresholds.Guignat L & Bertherat J, 2010 in Best Pract Res Clin Endocrinol Metab. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.