Synacthen® (corticotropin)

Definition

Synacthen® is the trade name of the active ingredient tetracosactide hexaacetate, which is marketed by Novartis Pharma. Tetracosane is the IUPAC name for a substance containing 24 carbon atoms. Tetracosactide is a protein molecule (peptide) consisting of 24 amino acids (AA) and is identical to the first 24 amino acids of the corticotropin ACTH (adrenocorticotropic hormone). Although ACTH, an endogenous hormone produced by the pituitary gland, consists of 39 amino acids, only the first 24 amino acids are important for its biological effect.

Significance as a doping agent

The use of corticotropins such as Synacthen is prohibited both in competition and out of competition, according to the WADA (World Anti-Doping Agency) Prohibited List, under Group S2: Hormones and Related Substances. 

Effects

Physiological effects
The physiological effects of Synacthen are identical to those of ACTH. ACTH is a hormone produced by the anterior pituitary gland and, in the human body, stimulates the synthesis and release of adrenal cortex hormones, particularly cortisol. It influences the immune system and, indirectly via cortisol levels, numerous metabolic processes.
The production and release of ACTH into the blood follows a daily rhythm (circadian rhythm) and is increased, amongst other things, during times of stress.

Diagnostic use
: Synacthen can be used as part of a stimulation test when adrenal insufficiency is suspected. This test assesses whether the adrenal cortex produces sufficient cortisol within a specified time (approximately 30 minutes) following an intravenous injection of approximately 250 µg of tetracosactide.

Therapeutic use
As an alternative to long-term glucocorticoid therapy for chronic polyarthritis (inflammation in multiple joints) and multiple sclerosis (an inflammatory and degenerative disease of the central nervous system), and for West syndrome (synonym: malignant infantile epilepsy).

Side effects

Stimulation of cortisol release may lead to side effects typical of corticosteroid therapy.
Source: Prescribing information for Synacthen®

Infections:
Increased susceptibility to infection, abscesses

; Blood and lymphatic system:
Leucocytosis

; Metabolism and nutrition:
Increased appetite, weight gain, sodium and water retention, hypokalaemia, hypocalcaemia.

Musculoskeletal system:
Osteoporosis, muscle weakness, steroid myopathy, pathological fractures of long bones, aseptic necrosis of the hip and humeral head, as well as vertebral compression fractures, tendon ruptures, loss of muscle mass.

Gastrointestinal tract:
Peptic ulcers (possibly with perforation and bleeding), pancreatitis, ulcerative oesophagitis, flatulence.

Skin:
Impaired wound healing, petechiae and ecchymoses, steroid acne, hyperpigmentation of the skin, increased sweating, thin, fragile skin (skin atrophy), erythema.

Central and peripheral nervous system:
Seizures, increased intracranial pressure with papilloedema (usually following treatment), dizziness, headache.

Psychiatric:
Risk of psychosis (development of delusions and hallucinations), mood disorders and sleep disturbances.

Endocrine system:
Cushing’s syndrome, growth disorders in children, hyperglycaemia, impaired glucose tolerance, manifestation of latent diabetes mellitus, hirsutism and signs of virilisation in women, menstrual disorders, adrenal haemorrhages, secondary adrenal and pituitary insufficiency.

Ophthalmological effects:
Development of cataracts, increased intraocular pressure, glaucoma, exophthalmos, macular degeneration.

Cardiovascular system:
Increased blood pressure, decompensation of existing heart failure, reversible myocardial hypertrophy in infants and young children.

Vascular system:
thromboembolism, necrotising vasculitis.

Kidneys and urinary tract:
formation of kidney stones, signs of adrenal insufficiency under particular stress; isolated cases of kidney damage have been reported.

References

Product information on Synacthen, Novartis Pharma, Aulendorf, Germany
; Roche Lexikon Medizin, Urban & Fischer