Corticotropin

(BAN, rINN)
Synonyms: ACTH; Adrenocorticotrophic Hormone; Adrenocorticotrophin; Corticotrophin; Corticotropina; Corticotropine; Corticotropinum; Kortikotropiini; Kortikotropin.
Cyrillic synonym: Кортикотропин.

💊 Chemical information

CAS — 9002-60-2 (corticotropin); 9050-75-3 (corticotropin zinc hydroxide); 8049-55-6 (corticotropin zinc hydroxide).
ATC — H01AA01.
ATC Vet — QH01AA01.

Pharmacopoeias.

In US as preparations for injection.

💊 Units

5 units of porcine corticotropin for bioassay are contained in about 50 micrograms (with lactose 5 mg) in one ampoule of the third International Standard (1962).

💊 Adverse Effects

Corticotropin stimulates the adrenals to produce cortisol (hydrocortisone) and mineralocorticoids; it therefore has the potential to produce similar adverse glucocorticoid and mineralocorticoid effects to those of the corticosteroids. In particular, its mineralocorticoid properties can produce marked sodium and water retention; considerable potassium loss may also occur. Corticotropin can induce sensitisation, and severe hypersensitivity reactions, including anaphylaxis, may occur. This is generally considered to be due to the porcine component of the peptide. Whereas corticosteroids replace endogenous cortisol (hydrocortisone) and thereby induce adrenal atrophy, corticotropin’s stimulant effect induces hypertrophy. Nevertheless, the ability of the hypothalamic-pituitaryadrenal axis to respond to stress is still reduced, and abrupt withdrawal of corticotropin may result in symptoms of adrenal insufficiency (see Withdrawal, below).
1. Riikonen R, Donner M. ACTH therapy in infantile spasms: side effects. Arch Dis Child 1980; 55: 664–72
2. Hanefeld F, et al. Renal and pancreatic calcification during treatment of infantile spasms with ACTH. Lancet 1984; i: 901
3. Riikonen R, et al. Disturbed calcium and phosphate homeostasis during treatment with ACTH of infantile spasms. Arch Dis Child 1986; 61: 671–6
4. Perheentupa J, et al. Adrenocortical hyporesponsiveness after treatment with ACTH of infantile spasms. Arch Dis Child 1986; 61: 750–3.

💊 Withdrawal

Corticotropin use may depress the hypothalamic-pituitary-adrenal axis. Abrupt withdrawal of corticotropin may therefore produce adrenocortical and pituitary unresponsiveness, and therapy should be stopped gradually. An increase in corticosteroid requirements associated with the stress of infection, or accidental or surgical trauma, may also precipitate acute adrenocortical insufficiency. See also Withdrawal under Corticosteroids.

💊 Precautions

As for Corticosteroids.

Phaeochromocytoma.

A hypertensive crisis in a patient given intravenous tetracosactide led to the discovery of an adrenaline-secreting phaeochromocytoma in a patient.1 It was suggested that caution should be observed when using corticotropin in patients with orthostatic hypotension in whom the diagnosis of phaeochromocytoma has not been excluded.
1. Jan T, et al. Epinephrine-producing pheochromocytoma with hypertensive crisis after corticotropin injection. Am J Med 1990; 89: 824–5.

💊 Interactions

Interactions seen with corticotropin are liable to be similar to those with corticosteroids.

💊 Uses and Administration

Corticotropin is a naturally occurring hormone of the anterior lobe of the pituitary gland. It stimulates the adrenal glands to secrete adrenocortical hormones, especially cortisol (hydrocortisone), some mineralocorticoids such as corticosterone, and, to a lesser extent, androgens. It has little effect on aldosterone secretion, which proceeds independently. Secretion of corticotropin by the functioning pituitary gland is controlled by the release of corticorelin from the hypothalamus and is also regulated by a negative feedback mechanism involving concentrations of circulating glucocorticoids. Conditions of stress may also stimulate secretion. Corticotropin may be used diagnostically to investigate adrenocortical insufficiency. It has also been used therapeutically in most of the conditions (with the exception of the adrenal deficiency states and adrenocortical overactivity) for which systemic corticosteroid therapy is indicated. Such use is now fairly limited. However, corticotropin may be used in certain neurological disorders such as infantile spasms and multiple sclerosis. The synthetic polypeptide tetracosactide, which has the same amino-acid sequence as the first 24 residues of human corticotropin, may be used as an alternative. Tosactide is another polypeptide analogue of corticotropin; it has the same sequence as the first 28 residues. Corticotropin has been available for injection in two forms. One form is a plain injection that may be given by the subcutaneous, intramuscular, or intravenous routes. The other form is a long-acting depot preparation in which the viscosity is increased by the addition of gelatin, and which is given subcutaneously or intramuscularly; it must not be given intravenously. Individual responses to therapeutic corticotropin vary considerably and doses must be adjusted accordingly. For diagnostic purposes the corticotropin test is based on the measurement of plasma-cortisol concentrations before and after injection. The plain preparation is used in doses of 10 to 25 units in 500 mL of glucose 5% infused intravenously over 8 hours. For therapeutic purposes typical initial doses for the depot preparation have been about 20 to 80 units every 24 to 72 hours by the subcutaneous or the intramuscular route. As soon as possible the dosage should be reduced gradually to the minimum necessary to control symptoms. A depot preparation of corticotropin combined with zinc hydroxide for intramuscular injection has been used in the past.

Epilepsy.

The use of corticotropin in the management of infantile spasms is referred to under Epilepsy in Corticosteroids.

Multiple sclerosis.

Short-term courses of corticotropin have been used to speed recovery from acute exacerbations of multiple sclerosis but corticosteroids, usually methylprednisolone, are now preferred.

Post-dural puncture headache.

There are anecdotal reports of the relief of post-dural puncture headache by corticotropin or tetracosactide, but a controlled study of tetracosactide use found no benefit.

💊 Preparations

USP 31: Corticotropin for Injection; Corticotropin Injection; Corticotropin Zinc Hydroxide Injectable Suspension; Repository Corticotropin Injection.

Proprietary Preparations

Arg.: Acthelea; Irl.: Acthar†; USA: Acthar.
Published November 09, 2018.