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Corticotropin and Tetracosactide

*Corticotropinum, Tetracosactidum*

For medical students2 min readUpdated 2026-10-10

Corticotropin is a polypeptide preparation of adrenocorticotropic hormone (ACTH) that stimulates adrenal cortex receptors and enhances the production of endogenous glucocorticoids. Its synthetic analog, tetracosactide, is also used in clinical practice due to its longer duration of action and lower immunogenicity. These agents are used to prevent adrenal atrophy and to treat a range of systemic disorders.

Substance naturePolypeptide of 39 amino acids (natural) or 24 amino acids (synthetic)

Target of actionSpecific receptors of the adrenal cortex

Duration6–8 hours for corticotropin; tetracosactide has a longer duration (once daily)

Route of administrationParenteral (primarily intramuscularly)

Mechanism of Action and Pharmacokinetics

Natural corticotropin is a polypeptide consisting of 39 amino acid residues obtained from the pituitary glands of cattle. The drug is administered parenterally (primarily intramuscularly), and its duration of action ranges from 6 to 8 hours.

The pharmacological effect is based on the following algorithm:

The drug binds to specific receptors in the adrenal cortex.
This stimulates the synthesis of own (endogenous) glucocorticoids.

The main disadvantage of the natural substance is its protein origin, which can lead to the formation of antibodies during therapeutic use.

Synthetic Analog: Tetracosactide

To reduce the risk of immune reactions, tetracosactide (Tetracosactidum) was developed as a synthetic polypeptide analog of ACTH. It consists of 24 amino acids and completely mirrors the N-terminal fragment of the native hormone while preserving all of its biological properties.

Comparison of natural and synthetic preparations:

Parameter	Corticotropin (Corticotropinum)	Tetracosactide (Tetracosactidum)
Origin	Natural (bovine pituitary)	Synthetic polypeptide
Molecular structure	39 amino acid residues	24 amino acid residues
Duration of effect	6–8 hours	Longer (up to once daily)
Safety	Antibodies form	Less prone to allergic reactions

Indications and Dosing Regimen

The main indication for natural corticotropin and tetracosactide is the prevention and treatment of secondary drug-induced adrenal cortical atrophy (management of withdrawal syndrome) that occurs following prolonged glucocorticoid therapy.

Additional indications for tetracosactide as part of combination therapy:

Connective tissue diseases (collagenoses);
Bronchial asthma;
Dermatoses;
Ulcerative colitis.

Important administration rule: ACTH therapy must be carried out strictly in courses. Long-term continuous administration is contraindicated, as it leads to adrenal cortex exhaustion.

Side Effects and Contraindications

Adverse effects are caused by excessive stimulation of the adrenal cortex and high levels of endogenous glucocorticoids and mineralocorticoids.

Main side effects:

Vascular and water-electrolyte: fluid retention (edema), arterial hypertension.
Metabolic: hyperglycemia, enhanced protein catabolism.
Immunological: antibody production and allergic reactions (characteristic of natural ACTH).

Contraindications:

Diabetes mellitus (due to diabetogenic action);
Peptic ulcer disease of the stomach and duodenum (risk of perforation and bleeding);
Heart failure (risk of worsening edema due to fluid retention);
Severe forms of arterial hypertension.

Mnemonic

Synthetic Tetracosactide consists of 24 amino acids and is administered once daily, eliminating the risk of antibody formation.

Frequently asked questions

Which specific adrenal cortex receptors does corticotropin bind to?

Corticotropin binds to specific G-protein-coupled membrane receptors located on the plasma membrane of adrenal cortex cells. The interaction of the hormone with these receptors leads to the activation of the adenylate cyclase system. As a result, ATP molecules are converted into the second messenger, cyclic adenosine monophosphate (cAMP). Subsequent accumulation of cAMP triggers a cascade of intracellular reactions that activate steroidogenesis enzymes and stimulate the hydrolysis of cholesterol esters in lipid droplets.

Synthesis of which adrenal cortex hormones does ACTH stimulate?

Adrenocorticotropic hormone stimulates the synthesis of corticosteroids in various zones of the adrenal cortex. Its primary effect is directed at glucocorticoid production, but the hormone also affects the synthesis of other steroids.

ACTH stimulates the synthesis of the following hormones:

Glucocorticoids — synthesized by cells of the zona fasciculata (primary representative is cortisol).
Mineralocorticoids — synthesized by cells of the zona glomerulosa (primary representative is aldosterone).
Androgens — synthesized by cells of the zona reticularis (include dehydroepiandrosterone, androstenedione, and testosterone).

Why is tetracosactide preferred over natural corticotropin?

Natural corticotropin is obtained from the pituitary glands of cattle, making it immunogenic and prone to causing antibody formation. Synthetic tetracosactide consists of 24 amino acids, is significantly less likely to cause allergic reactions, and has a longer duration of action.

Why are ACTH stimulants prescribed after prolonged glucocorticoid therapy?

Long-term administration of exogenous glucocorticoids suppresses adrenal function. ACTH preparations stimulate the production of endogenous hormones, preventing and reversing secondary drug-induced adrenal cortical atrophy ("withdrawal syndrome").

Why is treatment with tetracosactide performed only in courses?

Prolonged uncontrolled administration of ACTH stimulants leads to the exhaustion of the functional reserves of the adrenal cortex, making cyclical dosing mandatory.

In which diseases is corticotropin contraindicated?

The drug is contraindicated in diabetes mellitus, peptic ulcer disease of the stomach and duodenum, severe arterial hypertension, and heart failure.

Go deeper

Structural differences: 39 amino acids in natural ACTH versus 24 amino acids in tetracosactide
Mechanism of hyperglycemia and protein catabolism during adrenal cortex stimulation
Use of tetracosactide in the treatment of bronchial asthma, collagenoses, and ulcerative colitis
Risks of gastrointestinal complications (perforation and bleeding) during glucocorticoid hypersecretion
Pathophysiology of adrenal cortex exhaustion during continuous ACTH administration