Tetracosactide
Synthetic 24-amino-acid fragment of ACTH — FDA-approved as a diagnostic agent for adrenal insufficiency (Synacthen/cosyntropin stimulation test).
🔬 Mechanism of Action
Tetracosactide (cosyntropin) is a synthetic 24-amino-acid peptide corresponding to the first 24 residues of endogenous 39-amino-acid ACTH. These N-terminal 24 residues contain the full biological activity of ACTH. Upon IV or IM administration, it binds the melanocortin-2 receptor (MC2R) in the zona fasciculata of the adrenal cortex, activating adenylyl cyclase → cAMP → PKA pathway. This triggers acute steroidogenesis: cholesterol transport into mitochondria via StAR protein, followed by cortisol synthesis within 30-60 minutes. The standard 250 mcg dose produces supraphysiologic ACTH stimulation. A low-dose 1 mcg test may be more sensitive for detecting partial adrenal insufficiency.
Source: PMID: 6765449
📜Background & History
Tetracosactide (cosyntropin/Synacthen) is an essential diagnostic tool in endocrinology. The ACTH stimulation test has been the gold standard for diagnosing adrenal insufficiency for over 50 years. The short Synacthen test takes only 1 hour and can be performed in outpatient settings. Depot formulations (Synacthen Depot) have also been used therapeutically for infantile spasms and inflammatory conditions in various countries.
🎯 Research Use Cases
- ✓Adrenal insufficiency diagnosis
- ✓ACTH stimulation test
- ✓Infantile spasms (depot form)
- ✓Therapeutic use in inflammatory conditions
💉 Dosing Protocol
| Typical Dose | 250 mcg IV/IM (diagnostic) |
| Frequency | Single dose (ACTH stimulation test) |
| Half-Life | 0.25 hours |
⚠️Safety & Considerations
Generally well-tolerated as a single diagnostic dose. Rare allergic reactions possible. Depot formulations (Synacthen Depot) used therapeutically carry risks of adrenal suppression on withdrawal. Contraindicated in patients with adrenal carcinoma.
⚡Interactions & Contraindications
Exogenous corticosteroids will blunt the cortisol response and should be withheld before testing. Dexamethasone does not cross-react with cortisol assays.