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approvedHormone Regulation

Corticotropin

Also known as: ACTH, Adrenocorticotropic Hormone, Acthar Gel, H.P. Acthar Gel, Repository Corticotropin, Corticotrophin

Corticotropin (ACTH) is a 39-amino acid peptide hormone produced by the anterior pituitary that stimulates the adrenal cortex to synthesize and release cortisol, aldosterone, and adrenal androgens. The pharmaceutical form — H.P. Acthar Gel (repository corticotropin injection) — is an FDA-approved purified preparation that has been in clinical use since the 1950s, making it one of the oldest biologic drugs. It is approved for infantile spasms (West syndrome), multiple sclerosis exacerbations, nephrotic syndrome, rheumatic disorders, and other inflammatory conditions. Acthar Gel has been the subject of significant controversy due to its extreme pricing ($40,000+ per vial) despite being a decades-old drug.

3 cited references·5 researched benefits

Quick Answer

Corticotropin (ACTH/Acthar Gel) is a 39-amino acid pituitary hormone that stimulates the adrenal cortex to produce cortisol. FDA-approved since the 1950s, H.P. Acthar Gel is used for infantile spasms, MS exacerbations, and nephrotic syndrome. It works through melanocortin receptors (MC2R-MC5R), providing both glucocorticoid stimulation and direct anti-inflammatory effects beyond what cortisol alone achieves. Its extreme cost (~$40,000/vial) has generated significant controversy.

Key Facts

Mechanism
Corticotropin primarily activates the melanocortin 2 receptor (MC2R) on adrenocortical cells, stimulating steroidogenesis through the cAMP/PKA/StAR pathway, resulting in cortisol, aldosterone, and DHEA production. However, unlike exogenous glucocorticoids, ACTH also activates melanocortin receptors MC1R, MC3R, MC4R, and MC5R expressed on immune cells, neurons, and other tissues. MC1R activation on macrophages directly suppresses NF-kB signaling and pro-inflammatory cytokine production (TNF-alpha, IL-1, IL-6). MC3R/MC4R activation in the CNS modulates neuroinflammation and may contribute to the efficacy in infantile spasms and MS through mechanisms independent of adrenal steroidogenesis. This "melanocortin" pathway of anti-inflammatory activity is the proposed explanation for why ACTH sometimes demonstrates efficacy in patients who have failed equivalent doses of exogenous corticosteroids.
Research Status
approved
Half-Life
~10 minutes (plasma); depot gel provides sustained release over hours
Molecular Formula
C₂₀₇H₃₀₈N₅₆O₅₈S
Primary Use
Hormone Regulation
Table of Contents

Benefits

  • First-line treatment for infantile spasms (West syndrome) — superior to oral prednisolone in the UKISS trial for cessation of spasms and improved neurodevelopmental outcomesstrong
  • Treats acute MS exacerbations — FDA-approved alternative to high-dose IV methylprednisolone with comparable efficacy for relapse recoverystrong
  • Induces remission in nephrotic syndrome — effective in steroid-resistant and steroid-dependent nephrotic syndrome, possibly through direct melanocortin receptor effects on podocytesstrong
  • Anti-inflammatory effects beyond glucocorticoid action — melanocortin receptor activation on immune cells provides additional immunomodulation not replicated by synthetic corticosteroidsmoderate
  • Treats rheumatic conditions including rheumatoid arthritis, lupus, and gout flares — FDA-approved for multiple rheumatic/autoimmune indicationsmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intramuscular or subcutaneous (infantile spasms)150 IU/m² per day (high-dose) or 75 IU/m² per day (low-dose)Twice daily for 2-6 weeks, then taperStandard protocol based on UKISS trial. Treatment typically 2 weeks at full dose, then gradual taper over 2-4 weeks. Monitor blood pressure, glucose, and electrolytes. High-dose protocol shows faster spasm cessation.
Intramuscular or subcutaneous (MS exacerbation)80-120 unitsOnce daily for 2-3 weeksUsed when IV methylprednisolone is not feasible or has failed. Gel formulation allows IM or SC self-injection. Some protocols use 80 units daily for 5 days, then taper.
Intramuscular or subcutaneous (nephrotic syndrome)80 unitsEvery other day or twice weekly for 6 monthsUsed for steroid-resistant or frequently relapsing nephrotic syndrome. Response rates of 30-60% in steroid-resistant cases have been reported. Longer courses (up to 12 months) may be needed.
Intramuscular (gout flare)25-80 unitsSingle dose or every 8-12 hours for 1-3 daysAlternative to colchicine and NSAIDs for acute gout, particularly in patients with renal impairment or contraindications to standard therapy.

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

  • Cushingoid features — weight gain, moon facies, central obesity, striae, and skin fragility with prolonged use due to sustained cortisol elevationcommon
  • Hyperglycemia and diabetes — adrenal stimulation raises cortisol, which antagonizes insulin action; blood glucose monitoring requiredcommon
  • Hypertension and fluid retention — aldosterone and cortisol excess cause sodium retention and potassium wastingcommon
  • Immunosuppression and increased infection risk — cortisol-mediated immune suppression increases susceptibility to opportunistic infectionsserious
  • Irritability and behavioral changes in infants — commonly seen during treatment of infantile spasms; usually reversible after treatment completioncommon
  • Adrenal crisis upon abrupt discontinuation — chronic use suppresses the HPA axis; must taper gradually to avoid life-threatening adrenal insufficiencyserious

Frequently Asked Questions

Why is Acthar Gel so expensive?
H.P. Acthar Gel has been the subject of major pricing controversy. Originally available for a few dollars per vial, the price was raised to over $40,000 per vial through successive acquisitions — first by Questcor Pharmaceuticals (which raised the price from $40 to $28,000) and then by Mallinckrodt (which raised it further). The company argues the price reflects the cost of maintaining manufacturing of a complex biologic and funding clinical trials. Critics note that ACTH is a well-characterized hormone that has been available for 70+ years and that similar products are available internationally for a fraction of the price. The FTC investigated anti-competitive practices, and in 2023 Mallinckrodt emerged from bankruptcy. Generic alternatives and biosimilars have been in development.
How does ACTH work differently from prednisone?
While both result in elevated cortisol levels, ACTH has distinct mechanisms. ACTH stimulates the adrenal gland to produce all corticosteroids (cortisol, aldosterone, DHEA), not just cortisol, providing a more physiologic hormonal profile. More importantly, ACTH activates melanocortin receptors (MC1R, MC3R, MC4R, MC5R) on immune cells, neurons, and other tissues independently of its adrenal effects. MC1R activation on macrophages directly suppresses inflammation through NF-kB inhibition. This is why ACTH can sometimes work in patients who have failed equivalent doses of synthetic corticosteroids — the melanocortin pathway provides anti-inflammatory effects that exogenous steroids cannot replicate.
Why is ACTH preferred over steroids for infantile spasms?
The UKISS trial (2004) demonstrated that ACTH (or high-dose prednisolone) was superior to vigabatrin for cessation of infantile spasms and led to better neurodevelopmental outcomes at 14 months. ACTH specifically appears to suppress the pathologic neuronal hyperexcitability through both cortisol-mediated effects and direct melanocortin receptor activation in the brain. MC4R activation in the CNS modulates neuronal excitability and may directly counteract the epileptic mechanism. Current consensus guidelines from the Child Neurology Society recommend ACTH as first-line therapy for infantile spasms (excluding tuberous sclerosis complex, where vigabatrin is preferred).
Is corticotropin the same as cosyntropin?
They are related but different. Corticotropin (ACTH) is the full-length 39-amino acid hormone, available therapeutically as H.P. Acthar Gel for treating various conditions. Cosyntropin is the synthetic first 24 amino acids of ACTH (ACTH 1-24), used almost exclusively as a diagnostic agent for the ACTH stimulation test. Both have identical biological activity at the MC2R receptor on adrenal cells. The key practical differences are: Acthar Gel is a depot formulation for therapeutic use costing ~$40,000; cosyntropin is a single-dose diagnostic vial costing ~$50-100. Cosyntropin lacks the C-terminal residues 25-39 that may contribute to some of corticotropin's melanocortin receptor diversity.

References

  1. 1
    Treatment of infantile spasms: the United Kingdom Infantile Spasms Study (UKISS) comparing vigabatrin with prednisolone or tetracosactide(2012)PubMed ↗
  2. 2
    Adrenocorticotropic hormone therapy for nephrotic syndrome: a systematic review and meta-analysis(2014)PubMed ↗
  3. 3
    Melanocortin peptides: potential targets in the treatment of inflammatory disease(2007)PubMed ↗

Latest Research

Last updated: 2026-02-19