Alsactide

Synthetic ACTH Analog (tetracosactide)Rx: PrescriptionCompound: Approved

Also known as: Ac-ACTH(1-17)-NH2, ACTH 1-17 synthetic analogue, ACTH(1-24), Alsactide, Alsactide acetate, Cosyntropin, Synacthen, Synchrodyn, Tetracosactide

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

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Summary

Alsactide (tetracosactide) is a synthetic 17‑amino‑acid analogue of ACTH used primarily as a diagnostic stimulus for adrenal cortisol production and, experimentally, as a chronotherapy agent to boost morning glucocorticoid secretion. It is administered by injection (intramuscular, subcutaneous or intravenous) in microgram doses, exploiting its rapid, transient stimulation of cortisol without markedly affecting aldosterone or testosterone.

Mechanism of Action

Alsactide binds to the melanocortin‑2 receptor (MC2R) on adrenal zona fasciculata cells, mimicking endogenous ACTH. The peptide’s C‑terminal amide and the beta‑alanine/lysine substitutions increase receptor affinity, leading to activation of adenylate cyclase, cAMP accumulation and steroidogenic enzyme activation. The result is a selective rise in glucocorticoid (cortisol) synthesis, while mineralocorticoid output is modest at low doses.

What the Research Shows

Early chronobiology work showed that a 10 µg subcutaneous dose given at awakening transiently raised cortisol in healthy men without generating antibodies after repeated use. Dose‑response studies in ten males demonstrated that subcutaneous 8–10 µg and intravenous 2–8 µg doses reliably increased cortisol and progesterone, with higher subcutaneous doses also elevating aldosterone. Comparative trials found that 100 µg intramuscular alsactide produced a larger, shorter‑lasting cortisol surge than ACTH 1‑24, and that 15‑day daily dosing blunted ACTH responses to hypoglycemia. In Addison patients, alsactide did not alter endogenous ACTH, indicating no self‑inhibition. Melatonin co‑administration did not modify alsactide‑induced hormonal responses.

Reported Benefits

Clinical studies suggest alsactide can selectively and transiently enhance morning cortisol, which may help restore circadian adrenal rhythms in elderly or chronically ill individuals. Its rapid action and lack of antibody formation support repeated diagnostic testing (e.g., cosyntropin stimulation). Compared with longer ACTH fragments, the 1‑17 analogue yields a stronger, though brief, cortisol response, useful for assessing adrenal reserve.

Limitations of the Evidence

Evidence derives from small, short‑term trials in healthy volunteers and limited patient groups; long‑term safety and efficacy data are lacking. Low subcutaneous doses may be ineffective, and repeated daily dosing can blunt endogenous ACTH responses. Effects on mineralocorticoids are dose‑dependent, and the peptide is not approved for therapeutic cortisol replacement, limiting its use to diagnostic or experimental settings.

Safety Considerations

No antibodies were detected after repeated dosing in over 200 subjects, and no adverse events were reported in the cited studies. Nevertheless, as an ACTH agonist, alsactide can theoretically provoke cortisol excess, hyperglycaemia, fluid retention or hypertension, especially at higher doses. Caution is advised in patients with uncontrolled diabetes, hypertension, or conditions sensitive to glucocorticoids.

How It Is Administered

Alsactide is supplied for injection and may be given intramuscularly, subcutaneously or intravenously. Experimental protocols have used subcutaneous doses of 8–10 µg at awakening or intravenous doses of 2–8 µg. Diagnostic stimulation tests typically employ a single 10 µg intravenous or subcutaneous bolus.

Routes of Administration

IntramuscularIntravenousSubcutaneous

Goals & Uses

  • Adrenocortical function testingDiagnosticModerate
  • Anti-inflammatory therapyTherapeuticModerate
  • Adrenal insufficiency diagnosisEndocrinology / DiagnosticsHigh
  • ImmunosuppressionTherapeuticLow

Contraindications

  • Cushing's syndromeEndocrine DisorderHigh
  • Primary adrenocortical insufficiency (Addison's disease)Endocrine DisorderHigh
  • Hypersensitivity to peptideAllergyHigh
  • Active infectionsInfectious DiseaseModerate
  • Hypersensitivity to ACTH analoguesAllergy/ImmunologyHigh
  • Active peptic ulcer diseaseGastrointestinalModerate

Adverse Effects

  • HypokalemiaElectrolyteUncommon
  • HyperglycemiaMetabolicUncommonAbnormally high blood glucose
  • HypertensionCardiovascularUncommonHigh blood pressure
  • Injection site reactionsLocalCommon
  • Hypersensitivity/anaphylaxisImmunologicalRare
  • Nausea/vomitingGastrointestinalCommon
  • FlushingVascularCommonWarmth and redness of the skin
  • Transient hyperglycemiaMetabolic/EndocrineCommon
  • Fluid retention and edemaMetabolicUncommon

Drug Interactions

  • Exogenous glucocorticoidsModerate
  • Antidiabetic agentsModerate
  • NSAIDsModerateMay increase renal risk in susceptible patients
  • Diuretics (potassium-wasting)Moderate

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Pediatric patientsAgeRelative
  • Diabetes mellitusMetabolicRelative
  • Elderly patientsAgeRelative

Regulatory Status

  • European UnionApprovedApproved: Diagnostic testing of adrenal functionVarious brand names.
  • JPApprovedApproved: Diagnostic useMarketed as Alsactide.
  • United StatesApprovedApproved: ACTH stimulation testMarketed as Cosyntropin.
  • United KingdomUnknownTetracosactide (Synacthen) is the preferred ACTH analogue in the UK; alsactide approval status is unclear.

Approved in several jurisdictions for diagnostic use; marketed under various brand names (e.g., Cosyntropin, Synacthen).

Evidence & Sources

Frequently Asked Questions

What is the primary clinical use of alsactide?

Alsactide is most commonly employed as a diagnostic stimulus (cosyntropin test) to evaluate adrenal cortisol production. It is injected in a single microgram dose and cortisol levels are measured to assess adrenal reserve.

Can alsactide replace cortisol therapy in adrenal insufficiency?

Current evidence does not support therapeutic replacement. Studies have focused on short‑term cortisol stimulation and chronotherapy; long‑term efficacy and safety for hormone replacement have not been demonstrated.

Does repeated use of alsactide cause immune reactions?

In studies including more than 200 patients, repeated subcutaneous administration of 10 µg did not elicit detectable antibodies, indicating low immunogenicity under the tested conditions.

How does the timing of administration affect its effect?

Administering alsactide at the early morning (around 07:00) aligns with the natural cortisol peak and produces a selective, transient rise in cortisol, whereas timing at other circadian phases has not shown the same targeted effect.

Are there any known drug interactions?

The abstracts do not report specific drug interactions. However, because alsactide raises cortisol, concomitant use with agents that affect glucose metabolism, blood pressure, or immune function should be considered cautiously.

What is Alsactide used for?

Alsactide is educationally associated with: Adrenocortical function testing, Anti-inflammatory therapy, Adrenal insufficiency diagnosis, Immunosuppression. Educational only — not medical advice.

How is Alsactide administered?

Recorded routes of administration: Intramuscular, Intravenous, Subcutaneous.

What are the potential side effects of Alsactide?

Reported adverse effects include: Hypokalemia, Hyperglycemia, Hypertension, Injection site reactions, Hypersensitivity/anaphylaxis, Nausea/vomiting, Flushing, Transient hyperglycemia, Fluid retention and edema. This list is not exhaustive — consult a qualified clinician.

Who should avoid Alsactide?

Recorded contraindications: Cushing's syndrome, Primary adrenocortical insufficiency (Addison's disease), Hypersensitivity to peptide, Active infections, Hypersensitivity to ACTH analogues, Active peptic ulcer disease. Consult a qualified clinician before use.

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