Tetracosactide
Also known as: ACTH(1-24), Adrenocorticotropic hormone fragment, Cortrosyn, Cosyntropin, Synacthen, Synacthen Depot, Tetracosactide, Tetracosactrin
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Summary
Tetracosactide is a synthetic 1‑24 fragment of adrenocorticotropic hormone (ACTH) that activates the adrenal cortex. It is employed clinically to stimulate cortisol production for diagnostic testing of adrenal insufficiency and, in depot form, as hormonal therapy for infantile spasms (West syndrome).
Mechanism of Action
Tetracosactide binds the melanocortin‑2 receptor (MC2R) on adrenal zona fasciculata cells, mimicking endogenous ACTH. This activates adenylate cyclase, raises cAMP, and drives steroidogenic enzymes, leading to rapid synthesis and release of cortisol and other glucocorticoids. The cortisol surge underlies its diagnostic utility, while sustained exposure provides the hormonal effect used in infantile spasm treatment.
What the Research Shows
A 2022 review of primary adrenal insufficiency in Africa highlighted the tetracosactide stimulation test (cortisol >500‑550 nmol/L after injection) as a confirmatory diagnostic tool, though availability is limited. A 2025 double‑blind RCT in postpartum women with post‑dural puncture headache found a single 1 mg IV dose ineffective and associated with a slightly longer hospital stay. Cochrane reviews (2008, 2013) of infantile spasms identified several small RCTs indicating that hormonal regimens, including tetracosactide depot, achieve faster spasm cessation in more infants than vigabatrin, but study quality was poor. A 2020 meta‑analysis comparing ACTH/tetracosactide with prednisolone showed no clear superiority for spasm control or EEG normalization, with similar adverse‑event rates.
Reported Benefits
Evidence supports tetracosactide for confirming adrenal insufficiency via cortisol stimulation, providing a rapid, objective diagnostic read‑out. In infantile spasms, hormonal protocols that incorporate tetracosactide depot have been associated with higher early spasm‑resolution rates compared with vigabatrin alone, according to pooled analyses of available trials.
Limitations of the Evidence
Diagnostic utility depends on test availability; many low‑resource settings lack the reagent. Therapeutic data for infantile spasms stem from small, methodologically weak trials, limiting confidence in efficacy and long‑term benefit. No advantage over oral prednisolone has been demonstrated, and a recent RCT showed no benefit for post‑dural puncture headache. Large, well‑designed studies are lacking.
Safety Considerations
The postpartum headache trial reported no acute side‑effects after a single IV dose. Comparative analyses indicate that adverse events (irritability, increased appetite, weight gain, gastrointestinal upset) occur at similar frequencies to oral prednisolone, reflecting typical glucocorticoid‑related effects. Overall tolerability is acceptable, but clinicians should monitor for corticosteroid‑type reactions.
How It Is Administered
Tetracosactide is supplied for intramuscular, intravenous, or subcutaneous injection. Short‑acting formulations (e.g., cosyntropin) are used for diagnostic stimulation tests, while depot preparations (e.g., Synacthen Depot) are administered intramuscularly for therapeutic regimens in infantile spasms. Dosing schedules vary by indication and are defined in prescribing information.
Routes of Administration
Goals & Uses
- anti‑inflammatory therapyImmunomodulationLow
- Differentiation of primary vs. secondary adrenal insufficiencyDiagnosticHigh
- Diagnosis of adrenocortical insufficiencyDiagnosticHigh
- Therapeutic adrenal supportTherapeuticModerate
- Infantile spasms (West syndrome)NeurologyModerate
- Adrenal insufficiency diagnosisEndocrinology / DiagnosticsHigh
- Multiple sclerosis relapseTherapeuticModerate
- Treatment of inflammatory and autoimmune conditionsTherapeuticModerate
Contraindications
- Hypersensitivity to tetracosactide or ACTHAllergy/ImmunologicHigh
- Pregnancy (therapeutic use)ReproductiveModerate
- Cushing's syndromeEndocrine DisorderHigh
- Hypersensitivity to tetracosactideAllergyHigh
- Systemic infections (untreated)InfectiousHigh
- Active peptic ulcerGastrointestinalModerate
- Adrenocortical hyperfunctionEndocrineHigh
- Acute systemic fungal infectionInfectionModerate
Adverse Effects
- HyperglycemiaMetabolicUncommonAbnormally high blood glucose
- HypertensionCardiovascularUncommonHigh blood pressure
- Injection site reactionsLocalCommon
- HeadacheNeurologicUncommonPain in the head or upper neck
- Fluid retention / edemaFluid / ElectrolyteCommon
- Allergic/anaphylactic reactionImmunologicUncommon
- Cushing's syndrome features (with prolonged therapeutic use)EndocrineUncommon
- Transient hypercortisolismEndocrineCommon
- Flushing / facial erythemaVascularCommon
Drug Interactions
- Oral glucocorticoidsModerate
- Live vaccinesHigh
- CiclosporinModerate
- Antidiabetic agentsModerate
- CYP3A4 substratesLow
- NSAIDsModerateMay increase renal risk in susceptible patients
- Diuretics (potassium-wasting)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patients (infants)AgeRelative
- Pediatrics (<6 months)AgeRelative
- Patients with osteoporosisMusculoskeletalRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveRelative
- Diabetic PatientsMetabolicRelative
Regulatory Status
- European UnionApprovedApproved: diagnostic adrenal insufficiency testing, therapeutic adrenal supportMarketed as Synacthen.
- United StatesApprovedApproved: diagnostic adrenal insufficiency testingCosyntropin injectable, prescription only.
- United KingdomApprovedApproved: diagnostic adrenal insufficiency testingAvailable under NHS formularies.
Approved in the US (cosyntropin) for diagnostic use; approved in EU/UK (Synacthen) for both diagnostic and therapeutic indications.
Evidence & Sources
- Journal ArticleModerateMofokeng TRP, Beshyah SA, Ross IL2022-01-01T00:00:00.000000Z
- Journal ArticleModerateDziadzko M, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleHighHancock EC, Osborne JP, Edwards SW2013-01-01T00:00:00.000000Z
- Journal ArticleHighHancock EC, Osborne JP, Edwards SW2008-01-01T00:00:00.000000Z
- Journal ArticleHighLi S, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleModerateO'Callaghan FJ, et al.2017-01-01T00:00:00.000000Z
Frequently Asked Questions
What clinical situations call for tetracosactide?
It is used to provoke cortisol release for the adrenal stimulation test when adrenal insufficiency is suspected, and in depot form as part of hormonal therapy for infantile spasms.
How does tetracosactide differ from natural ACTH?
Tetracosactide comprises the first 24 amino acids of ACTH, retaining full activity at the melanocortin‑2 receptor, allowing it to stimulate adrenal cortisol production similarly to the native hormone.
Is tetracosactide effective for treating post‑dural puncture headache?
A double‑blind randomised trial in postpartum women found a single 1 mg IV dose did not reduce the need for epidural blood patch or improve headache severity, indicating no therapeutic benefit for this condition.
How does tetracosactide compare with prednisolone for infantile spasms?
A meta‑analysis of six RCTs showed tetracosactide was not superior to prednisolone in achieving spasm cessation or EEG normalization, with comparable rates of common side‑effects.
What side‑effects should be watched for?
Adverse events resemble those of systemic steroids, including irritability, increased appetite, weight gain, and gastrointestinal upset; serious corticosteroid effects are possible with prolonged use, so monitoring is advised.
What is Tetracosactide?
Tetracosactide is a synthetic 1‑24 fragment of adrenocorticotropic hormone (ACTH) that activates the adrenal cortex. It is employed clinically to stimulate cortisol production for diagnostic testing of adrenal insufficiency and, in depot form, as hormonal therapy for infantile spasms (West syndrome).
What is Tetracosactide used for?
Tetracosactide is educationally associated with: anti‑inflammatory therapy, Differentiation of primary vs. secondary adrenal insufficiency, Diagnosis of adrenocortical insufficiency, Therapeutic adrenal support, Infantile spasms (West syndrome), Adrenal insufficiency diagnosis, Multiple sclerosis relapse, Treatment of inflammatory and autoimmune conditions. Educational only — not medical advice.
How is Tetracosactide administered?
Recorded routes of administration: Intramuscular, Intravenous, Subcutaneous.
What are the potential side effects of Tetracosactide?
Reported adverse effects include: Hyperglycemia, Hypertension, Injection site reactions, Headache, Fluid retention / edema, Allergic/anaphylactic reaction, Cushing's syndrome features (with prolonged therapeutic use), Transient hypercortisolism, Flushing / facial erythema. This list is not exhaustive — consult a qualified clinician.
Who should avoid Tetracosactide?
Recorded contraindications: Hypersensitivity to tetracosactide or ACTH, Pregnancy (therapeutic use), Cushing's syndrome, Hypersensitivity to tetracosactide, Systemic infections (untreated), Active peptic ulcer, Adrenocortical hyperfunction, Acute systemic fungal infection. Consult a qualified clinician before use.