July 7, 2020
Standard Short Synacthen Test for Suspected Adrenal Failure Minimize

Standard Short Synacthen test for suspected adrenal failure


This is performed for the investigation of adrenal insufficiency. See also under Synacthen test for congenital adrenal hyperplasia. There is no evidence to support the use of this test in the management of steroid replacement or withdrawal.


The Synacthen test gives unreliable results within 2 weeks of pituitary surgery.


Adrenal glucocorticoid secretion is controlled by adrenocorticotrophic hormone (ACTH) released by the anterior pituitary. This test evaluates the ability of the adrenal cortex to produce cortisol after stimulation by synthetic ACTH (tetracosactide; Synacthen ®). It does not test the whole pituitary-adrenal axis. The short test assesses the ability of the adrenal gland to respond to ACTH but is not reliable within 2 weeks of pituitary surgery.

Side effects

There are rare reports of hypersensitivity reactions to ‘Synacthen’ particularly in children with history of allergic disorders.


There are no dietary restrictions for this test. This test should be performed in the morning as the cortisol responses between the morning and late afternoon may differ by as much as 100 nmol/L at 30 min sample post Synacthen.

Prednisolone should be stopped 24 hours before the Synacthen test.


  • 2 plain tubes
  • 250 microgram Synacthen (1 vial)
  • the dose for children is 36 microgram/kg body weight up to a maximum of 250 micrograms



take 3 mL blood for cortisol
inject Synacthen iv or im


take further sample for cortisol


  1. Adrenal insufficiency is excluded by an incremental rise in cortisol of > 200 nmol/L and a 30 min value > 600 nmol/L.
  2. The above definition only defines adrenal insufficiency. The definition of normality is problematic since there is considerable variation in healthy individuals and a significant overlap with patients who have adrenal insufficiency.
  3. In ACTH deficiency the response to the short test may be normal or reduced.
  4. The response to Synacthen is not affected by obesity.
  5. There is no difference in cortisol response between iv & im administration.
  6. Baseline and incremental cortisol values do NOT apply to women taking oral contraceptives or to pregnant women.
  7. There is quite marked variation in the measurement of cortisol in the post-Syancthen samples by different laboratory methods (Clark et al 1988).

Sensitivity and Specificity

There are reports of patients with incipient adrenal failure with normal responses to Synacthen. The use of physiological doses eg 1 microgram may prove more useful at determining those subjects with poor responses than conventional (250 microgram) pharmacological doses.

The review by Dorin et al suggests that the standard test is better for diagnosing primary adrenal insufficiency. However, whilst there is no difference in diagnostic performance between the standard and low dose tests in cases of secondary adrenal insufficiency, neither test is recommended where there is a possibility of pituitary dysfunction.


  • Azziz R, Zacur HA, Parker CR Jr, Bradley EL Jr, Boots LR. Effect of obesity on the response to acute adrenocorticotropin stimulation in eumenorrhoeic women. Fertil Steril 1991;56:427-33.
  • Clarke PMS, Neylon I, Raggatt PR, Sheppard MC, Stewart PM. Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamo-pituitary disorders. Clin Endocrinol (Oxf) 1998;49:287-292.
  • Dorin RI, Qualls CR, Crapo LM. Diagnosis of Adrenal Insufficiency. Ann Intern Med 2003;139:194-204.
  • Ostlere LS, Rumsby G, Holownia P, Jacobs HS, Rustin HA, Honour JW. Carrier status for steroid 21-hydroxylase deficiency is only one factor in the variable phenotype of acne. Clin Endocrinol (Oxf) 1998;48:209-215.
  • Patel SR, Selby C, Jeffcoate WJ. The short synacthen test in acute hospital admissions. Clin Endocrinol 1991;35:259-61.
  • Reingold A, Guillemant S, Ghata NJ, Guillemant J, Touitou Y, Dupont W, Lagoguey M, Bourgeois P, Briere L, Fraboulet G, Guillet P.. Clinical chronopharmacology of ACTH 1-17. 1 effects on plasma cortisol and urinary 17-hydroxycorticosteroids. Chronobiologica 1980;17:513-523.
  • Suri D, Moran J, Hibbard JU, Kasza K, Weiss RE. Assessment of adrenal reserve in pregnancy: defining the normal response to the adrenocorticotropin stimulation test. JCEM 2006;91:3866-3872.

JHB 9 June 2012


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