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Short Synacthen Test


Used in the diagnosis of hypoadrenalism as a screening test.
It is an increasingly used alternative to the insulin tolerance test to diagnose secondary hypoadrenalism due to pituitary hypofunction.
May also be used to ascertain that the adrenals are functioning normally after a prolonged course of corticosteroids.
Diagnosis and characterization of 21-hydroxylase deficiency and other causes of adrenal hyperplasia.


Not needed for hypoadrenalism if random cortisol > 550nmol/l. If a random cortisol . 450, patients are very likely to pass the short synacthen test, and some feel that in this circumstance, the test is not warranted.




If on steroids ensure that none is taken the night prior to the test. The final dose should be at 9am, 24 hrs prior to the test.
Admission is required if there is a risk of Addisonian crisis (virtually never).
19g cannula
Saline flush
10ml syringes x 4
3 red top Vacutainers for cortisol (same samples for 17-OH progesterone)
1 EDTA tube (purple top Vacutainer) for ACTH basal sample.
1 ampoule of 250 micrograms tetracosactrin (Synacthen)


  1. 0900h: take 7 ml blood for cortisol (red top Vacutainer) and ACTH (purple top, on ice to lab immediately).
  2. Give 250micrograms tetracosactrin IM (ideally) or IV.
  3. 0930h: Take 7 ml blood for cortisol.
  4. 1000h: Take 7 ml blood for cortisol.
  5. For the diagnosis of congenital adrenal hyperplasia the samples taken for cortisol are also analysed for 17-OH progesterone to exclude 21-hydroxylase deficiency. In some cases 17-OH pregnenolone is measured to differentiate between 21-OH and 3ß-HSD deficiency.


Normal response if test done at 0900h (considerable diurnal variation):
Stimulated plasma cortisol >550 nmol/l
Incremental rise of at least 170 nmol/l

  • If impaired cortisol response, and ACTH >200 ng/l then diagnosis is primary adrenal failure.
  • If ACTH <10ng/l then diagnosis is secondary adrenal failure
  • Response of 17-OH progesterone in suspected 21-hydroxylase deficiency (cryptic): marked rise after ACTH stimulation, which varies according to whether the patient is homozygous or heterozygous. Reference for nomogram: New et al., JCEM 57, 320-326 (1983).


A normal cortisol response does not exclude adrenal failure, since impending adrenal failure might be associated with a much greater loss of zona glomerulosa function. The latter would be suggested by an elevated plasma renin activity.
If equivocal result and no urgency, repeat test after a few weeks.
An abnormal response is consistent with primary or secondary adrenal failure, and should be investigated further. Consider long synacthen test or pituitary function testing.


Clayton R.N., BMJ 298, 271-272 (1989).
Burke C.W., Clin. Endo. Metab. 14, 947-976 (1985).
Adrenal hyperplasia
Savage M.O., Clin Endo. Metab. 14, 893-907 (1985).