Peptides›Cognitive, Immune›ACTH 1-24

ACTH 1-24

/ Synthetic 24-residue N-terminal fragment of ACTH (corticotropin); MC2R agonist

TIER 1 · ClinicalN = 0 · TESTING PENDINGMW 2934.00 g·mol⁻¹

ALIAS · Tetracosactide · Synacthen (trade) · Cosyntropin (trade — US) · ACTH(1-24)

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceSYSMEHFRWGKPVGKKRRPVKVYP

MW · 2934.00CLASS · Synthetic 24-residue N-terminal fragment of ACTH (corticotropin); MC2R agonistCATEGORY · Cognitive, Immune

Tier 1 for the FDA-approved diagnostic indication. Cosyntropin (synthetic ACTH 1-24) is the standard reagent for the rapid ACTH stimulation test used to diagnose primary and secondary adrenal cortical insufficiency. The depot formulation Synacthen Depot is approved in many EU countries for inflammatory and autoimmune indications and for infantile spasms; depot formulations are not currently FDA-marketed in the US.

§ B · Mechanism of action

ACTH 1-24 reproduces the bioactive N-terminal sequence of native 39-residue corticotropin and binds the melanocortin 2 receptor (MC2R) on adrenocortical zona fasciculata cells. MC2R activation drives cAMP-dependent steroidogenesis, with cortisol release as the principal downstream readout used in the diagnostic stimulation test. The truncated analog removes the C-terminal residues that account for most of the immunogenicity of porcine-derived full-length ACTH preparations.

§ C · Human clinical evidence

Tier 1 for the diagnostic indication. The 250 microgram intravenous or intramuscular cosyntropin stimulation test, with cortisol measurement at 30 and 60 minutes, is the reference standard for evaluating adrenal cortical reserve and is recommended in Endocrine Society and other society guidelines. Depot formulations have published evidence in infantile spasms and selected inflammatory indications outside the US.

§ D · Primary literature

PubMed26760044Bornstein SR et al. — Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline · The Journal of Clinical Endocrinology and Metabolism · systematic-reviewClinical practice guideline establishing the 250 microgram cosyntropin stimulation test as the reference diagnostic procedure for primary adrenal insufficiency, with cortisol thresholds and assay considerations.Limitations: Guideline document, not a primary trial; thresholds depend on assay platform.2016

PubMed18697868Kazlauskaite R et al. — Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis · The Journal of Clinical Endocrinology and Metabolism · meta-analysisMeta-analysis comparing 250 microgram and low-dose 1 microgram cosyntropin stimulation tests for secondary adrenal insufficiency; both offered useful diagnostic accuracy with the high-dose test more standardised.Limitations: Heterogeneous reference standards across included studies; cortisol assay variability.2008

§ F · Safety signal

Acute administration of synthetic ACTH 1-24 has a well-characterised safety profile dominated by rare hypersensitivity (lower than full-length porcine ACTH but not absent). Chronic use of depot formulations carries the expected glucocorticoid-excess profile (hypertension, hyperglycaemia, immunosuppression, fluid retention) because the downstream effect is sustained cortisol elevation.

§ H · Regulatory status

Regulatory status

FDA status:: FDA-approved
Compounding:: Not eligible for compounding (approved, not in shortage)

§ I · Notable gaps and controversies

The diagnostic role is well established and uncontested. Confusion sometimes arises between cosyntropin (ACTH 1-24, FDA-approved diagnostic) and Acthar Gel (full-length porcine ACTH 1-39, FDA-approved for infantile spasms and several inflammatory indications) — these are different molecules with different regulatory status, supply chains, and pricing. Vendor channels selling 'ACTH' or 'tetracosactide' research material do not provide the identity, sterility, and endotoxin assurance required for clinical-grade diagnostic use.