What is a Synacthen (tetracosactide) injection?

Synacthen (Tetracosactide) Injection

Synacthen (tetracosactide) is a synthetic analogue of adrenocorticotropic hormone (ACTH 1-24) primarily used as a diagnostic agent to assess adrenal function through the short Synacthen test for diagnosing adrenal insufficiency. 1, 2

What is Synacthen?

• Synacthen contains tetracosactide (also called tetracosactrin), a synthetic polypeptide that replicates the first 24 amino acids of natural ACTH (ACTH 1-24) 1, 3
• It stimulates the adrenal cortex to produce cortisol, mimicking the action of natural ACTH 2
• Available in two formulations:
  • Standard Synacthen for immediate release 4
  • Synacthen Depot, a slow-release formulation 4

Clinical Applications

Primary Use: Diagnostic Testing

• The standard short Synacthen test involves administering 0.25 mg of tetracosactide intramuscularly or intravenously 2
• Cortisol levels are measured at baseline and 30 minutes after administration 2, 3
• A peak cortisol value above 500 nmol/L (18 μg/dL) is considered a normal response 2
• Used to diagnose both primary and secondary adrenal insufficiency 2, 5

Specific Diagnostic Scenarios

• Evaluation of suspected adrenal insufficiency in patients with hypo-osmolar hyponatremia 2
• Distinguishing between primary adrenal insufficiency (low cortisol, high ACTH) and secondary adrenal insufficiency (low cortisol, low ACTH) 2, 6
• Assessment of adrenal function in patients on long-term steroid therapy 3
• Evaluation of suspected hypophysitis, particularly in patients receiving immune checkpoint inhibitor therapy 5

Test Interpretation

• The "6 (5), 7,18" rule can be applied for interpretation 3:
  • Basal cortisol should not be lower than 6 μg/100 ml (5 μg/100 ml in afternoon/evening)
  • Increment should not be less than 7 μg/100 ml
  • Post-stimulation cortisol should not be less than 18 μg/100 ml
• Failure to meet at least two of these criteria suggests adrenal insufficiency 3

Clinical Considerations

• In cases of suspected adrenal crisis, treatment should not be delayed for diagnostic testing 2, 5
• Relative adrenal insufficiency (increase in serum cortisol of <9 μg/dL after Synacthen administration) is common in patients with cirrhosis and is associated with higher mortality and complications 7
• Exogenous steroid use can confound test results 2
• The test is considered safe, with studies reporting no adverse effects in hundreds of patients 3

Alternative Options

• In countries where Synacthen is not available, long-acting porcine sequence ACTH 1-39 (Acton Prolongatum®) can be used as an alternative diagnostic agent 8
• A serum cortisol cutoff value of 19.5 μg/dL at 120 minutes following stimulation with Acton Prolongatum® showed high diagnostic accuracy compared to the short Synacthen test 8

Therapeutic Applications

• Beyond diagnosis, synthetic ACTH analogs like tetracosactide have been used therapeutically in some conditions 9
• Low-dose regimens (1 mg intramuscularly weekly) have been studied in nephrotic syndrome patients unresponsive to conventional treatments 9

Precautions

• Potential side effects include fluid retention, which may require discontinuation of treatment in some cases 9
• Monitoring for hyperglycemia and hypokalemia is recommended, though these complications are rare at diagnostic doses 9