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Corticotrophins (Tetracosactide and ACTH)

Corticotrophin (ACTH) is a peptide produced by the pituitary gland and is released into the circulation and stimulates production of corticosteroids from the adrenal glands. Tetracosactrin (synacthen) is an analogue of corticotrophin.1

Uses

  • Main use is as a diagnostic tool.2

The following are older uses of Tetracosactrin (as an anti-inflammatory):

  • Treatment of allergic disorders
  • Inflammatory eye disorders
  • Severe skin disorders
  • Gastrointestinal disorders e.g. depot tetracosactide still licensed for short-term use in inflammatory bowel disease
  • Some rheumatic disorders e.g. depot tetracosactide still licensed for short-term use in juvenile rheumatoid arthritis, rheumatoid arthritis and osteoarthritis

However, their use as anti-inflammatory agents has largely been outdated, as they have unpredictable therapeutic responses; therefore corticosteroids tend to be used.

Short and long synacthen test

Synacthen is given and cortisol levels are measured. Failure of the cortisol level to rise after administration of synacthen indicates adrenocortical insufficiency.

How the test is performed

This is one example.

  1. Take a baseline sample of cortisol - at 09:00.
  2. Then administer 250 mcg synacthen either iv / im.
  3. Then take a further sample for plasma cortisol at 30 minutes post synacthen administration.

Interpreting results

  • An adequate response to synacthen is defined as a post-stimulation peak cortisol value of 500 nmol/l at either 30 or 60 min with an increase in cortisol levels of at least 200nmol/l.3 However, see your local laboratory for ranges.
  • If the results are equivocal they should be discussed with the local endocrinologist. Rarely a long synacthen test is performed following an abnormal short synacthen test.4

Example regimen of long synacthen test

  • Basal plasma cortisol and ACTH measured at 09:00.
  • 1 mg synacthen given as a depot, intramuscularly.
  • Plasma cortisol measures taken at exactly 30 minutes, 1, 2, 4, 7 and 24 hours after injection of synacthen.

Results: In primary adrenocortical insufficiency (i.e. Addison's disease) the plasma cortisol fails to rise (see local laboratory for cut-off, but "normal" peak is usually in the order around 800 - 1000nmol per litre). However, in secondary causes a delayed rise is observed e.g. chronic steroid use.5

However, long synacthen test is rarely performed nowadays as more sensitive assays that measure ACTH are now available.

Document references
  1. Summary of Product Characteristics - Synacthen® Ampoules 250mcg, (Tetracosactide acetate) Alliance Pharmaceuticals Updated Feb 2005, electronic Medicines Compendium
  2. Gleeson HK, Walker BR, Seckl JR, et al; Ten years on: Safety of short synacthen tests in assessing adrenocorticotropin deficiency in clinical practice.; J Clin Endocrinol Metab. 2003 May;88(5):2106-11. [abstract]
  3. Dorin RI, Qualls CR, Crapo LM; Diagnosis of adrenal insufficiency. Ann Intern Med. 2003 Aug 5;139(3):194 [abstract]
  4. Summary of Product Characteristics - Synacthen® Depot (Tetracosactide acetate PhEur 1mg/ml) Alliance Pharmaceuticals Updated Feb 2007; electronic Medicines Compendium
  5. University of Dundee; Long Synacthen Test
AcknowledgementsEMIS is grateful to Dr Gurvinder Rull for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 306
Document Version: 2
DocRef: bgp25175
Last Updated: 19 Mar 2008
Review Date: 19 Mar 2009
















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