Corticotropin
Also known as: ACTH, Acthar, Adrenocorticotropic hormone, Corticotrophin, Corticotropin, Cosyntropin, H.P. Acthar Gel, Repository corticotropin injection, Synacthen
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Summary
Corticotropin, also known as adrenocorticotropic hormone (ACTH), is a pituitary-derived peptide that stimulates the adrenal cortex to produce cortisol and other steroids. It is prescribed as an injectable drug and is primarily employed in clinical practice to assess adrenal function and to help differentiate causes of Cushing syndrome. The hormone is part of the hypothalamic‑pituitary‑adrenal (HPA) axis, and its measurement or administration provides insight into endocrine disorders.
Mechanism of Action
ACTH binds to the melanocortin‑2 receptor (MC2R) on adrenal zona fasciculata cells. Receptor activation triggers adenylate cyclase, raising intracellular cAMP, which activates protein kinase A and drives the transcription of steroidogenic enzymes. The resulting cascade increases synthesis and secretion of cortisol, aldosterone precursors, and adrenal androgens, thereby mediating the hormone's physiological and diagnostic effects.
What the Research Shows
The peer‑reviewed literature cited highlights ACTH’s role within the HPA axis and its diagnostic utility. A historical overview describes the discovery of corticotropin and its receptors, underscoring its central place in stress and metabolic regulation. A review of Cushing syndrome notes that plasma ACTH levels help distinguish ACTH‑dependent from ACTH‑independent hypercortisolism, guiding imaging and treatment decisions. In a large septic‑shock trial, patients were stratified by response to an ACTH stimulation test, illustrating its use as a functional assay. No randomized therapeutic trials of ACTH itself are reported in the provided abstracts.
Reported Benefits
Evidence supports ACTH as a reliable tool for adrenal function testing. Measuring cortisol response after ACTH injection helps diagnose primary adrenal insufficiency and differentiates ACTH‑dependent versus independent Cushing syndrome, informing appropriate imaging and therapeutic pathways. Its use in clinical protocols, such as the septic‑shock study, demonstrates practical value in patient stratification.
Limitations of the Evidence
The cited literature does not provide data on ACTH as a therapeutic agent for disease modification; its role is confined to diagnostic testing. No randomized controlled trials evaluating ACTH treatment outcomes are presented, limiting conclusions about efficacy beyond endocrine assessment. Consequently, its benefits are restricted to diagnostic contexts rather than disease cure or symptom relief.
Safety Considerations
The abstracts do not detail adverse events related to ACTH administration. While ACTH can theoretically provoke cortisol excess, hypertension, hyperglycemia, or electrolyte shifts, such effects are not described in the provided sources. Clinicians should therefore rely on product labeling and broader pharmacovigilance data for safety guidance, as the current literature offers limited safety information.
How It Is Administered
Corticotropin is supplied as a sterile injectable formulation and may be administered intramuscularly, intravenously, or subcutaneously. Dosing regimens vary according to the specific diagnostic protocol (e.g., standard ACTH stimulation test) and are determined by the prescribing clinician. The drug is stored according to manufacturer instructions and reconstituted immediately before use.
Routes of Administration
Goals & Uses
- Manage multiple‑sclerosis relapseTherapeuticModerate
- Nephrotic syndromeNephrologyModerate
- Infantile spasms (West syndrome)NeurologyHigh
- Control infantile spasmsTherapeuticHigh
- Adrenal insufficiency diagnosisEndocrinology / DiagnosticsHigh
- Acute gout flareRheumatologyModerate
- Rheumatic and collagen disordersRheumatology / ImmunologyModerate
- Stimulate adrenal cortisol production in adrenal insufficiencyTherapeuticModerate
- Diagnostic adrenal function testingDiagnosticHigh
- Multiple sclerosis acute exacerbationNeurology / ImmunologyModerate
Contraindications
- Known hypersensitivity to ACTH or formulation componentsAllergyHigh
- Live or live-attenuated vaccinesImmunologyHigh
- Systemic fungal infectionInfectionModerate
- Adrenocortical insufficiency or hyperfunctionEndocrinologyHigh
- OsteoporosisMusculoskeletalModerate
- SclerodermaAutoimmuneHigh
- Systemic fungal infectionsInfectious DiseaseHigh
- Uncontrolled hypertensionCardiovascularModerate
Adverse Effects
- EdemaFluid BalanceUncommonSwelling from fluid retention
- Cushingoid appearance (weight gain, moon face)EndocrineUncommon
- HypokalemiaElectrolyteCommon
- HyperglycemiaMetabolicCommonAbnormally high blood glucose
- HypertensionCardiovascularCommonHigh blood pressure
- Injection site pain/rednessLocalCommon
- Immunosuppression / increased infection riskImmunologyCommon
- HPA axis suppressionEndocrineCommon
- Skin hyperpigmentationDermatologicUncommon
- Cushing's syndrome / hypercortisolismEndocrineCommon
Drug Interactions
- NSAIDs (e.g., aspirin, ibuprofen)Moderate
- CYP3A4 inhibitors (e.g., ketoconazole)Moderate
- Vaccines (live)High
- Concurrent glucocorticoidsHigh
- Diuretics (thiazides, loop diuretics)Moderate
- Antidiabetic agents (insulin, oral hypoglycemics)Moderate
- Anticoagulants (warfarin)Moderate
Population Constraints
- Patients with active or latent tuberculosisInfectious DiseaseRelative
- PregnancyReproductive SafetyRelative
- ElderlyAgeRelative
- Pediatric infants (≤2 months) for infantile spasmsAgeAbsolute
- Pediatric patients (neonates/infants)PediatricRelative
- Patients with diabetes mellitusMetabolicRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveRelative
Regulatory Status
- European UnionUnapprovedACTH not marketed as a therapeutic product; used off‑label in some countries.
- United StatesApprovedApproved: infantile spasms, multiple sclerosis relapse, diagnostic adrenal testingACTH gel (H.P. Acthar Gel) and cosyntropin 1‑24 are FDA‑approved.
- United KingdomUnapprovedNo licensed ACTH product; limited clinical use.
FDA‑approved ACTH gel (H.P. Acthar Gel) for infantile spasms, multiple‑sclerosis relapse, and certain inflammatory disorders; synthetic ACTH 1‑24 (cosyntropin) approved for diagnostic adrenal testing.
Evidence & Sources
- Journal ArticleHighSiefried KJ, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleModerateSarafoglou K, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateMiller WL2018-01-01T00:00:00.000000Z
- Journal ArticleModerateReincke M, Fleseriu M2023-01-01T00:00:00.000000Z
- Journal ArticleModerateAuchus RJ, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateSprung CL, et al.2008-01-01T00:00:00.000000Z
Frequently Asked Questions
What is the primary clinical use of corticotropin?
Corticotropin is primarily used as a diagnostic agent to stimulate cortisol production, allowing clinicians to assess adrenal gland function and to differentiate ACTH‑dependent from ACTH‑independent causes of Cushing syndrome.
Is ACTH approved for treating any disease?
The abstracts provided do not report therapeutic trials of ACTH for disease treatment, so its approved uses appear limited to diagnostic testing rather than direct disease therapy.
How is the ACTH stimulation test performed?
A standard dose of injectable ACTH is given intravenously, intramuscularly, or subcutaneously, and blood cortisol levels are measured before and after administration (typically at 30 and 60 minutes) to evaluate adrenal responsiveness.
What are common side effects of ACTH administration?
The cited literature does not describe side effects. Known pharmacologic effects can include transient increases in blood pressure, blood glucose, and electrolyte changes, but clinicians should consult detailed product information for safety data.
Can ACTH be used to treat Cushing syndrome?
No. ACTH levels are used to diagnose and classify Cushing syndrome, but the hormone itself is not a treatment; management focuses on surgery, steroidogenesis inhibitors, or other targeted therapies.
What is Corticotropin used for?
Corticotropin is educationally associated with: Manage multiple‑sclerosis relapse, Nephrotic syndrome, Infantile spasms (West syndrome), Control infantile spasms, Adrenal insufficiency diagnosis, Acute gout flare, Rheumatic and collagen disorders, Stimulate adrenal cortisol production in adrenal insufficiency, Diagnostic adrenal function testing, Multiple sclerosis acute exacerbation. Educational only — not medical advice.
How is Corticotropin administered?
Recorded routes of administration: Intramuscular, Intravenous, Subcutaneous.
What are the potential side effects of Corticotropin?
Reported adverse effects include: Edema, Cushingoid appearance (weight gain, moon face), Hypokalemia, Hyperglycemia, Hypertension, Injection site pain/redness, Immunosuppression / increased infection risk, HPA axis suppression, Skin hyperpigmentation, Cushing's syndrome / hypercortisolism. This list is not exhaustive — consult a qualified clinician.
Who should avoid Corticotropin?
Recorded contraindications: Known hypersensitivity to ACTH or formulation components, Live or live-attenuated vaccines, Systemic fungal infection, Adrenocortical insufficiency or hyperfunction, Osteoporosis, Scleroderma, Systemic fungal infections, Uncontrolled hypertension. Consult a qualified clinician before use.