July 14, 2020
Depot (Prolonged) 'Synacthen' Test Minimize

Depot (Prolonged) 'Synacthen' test


This is performed for the differentiation of primary from secondary adrenal failure. The ready availability of ACTH assays may now make this test protocol redundant.



The long Synacthen test protocol was designed to confirm the diagnosis of primary adrenal failure. The diagnosis of adrenal failure is made on the cortisol response to ACTH at 30 min (see short Synacthen test). The prolonged stimulation of the adrenals by ACTH in this test results in a degree of recovery by adrenal glands which have become atrophic due to pituitary failure; whereas, adrenal glands that are themselves diseased will not respond.

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. However, those patients who are already taking corticosteroids should have been taking them for less than 2 weeks and should be switched to dexamethasone 24 hours before the test.


  • 6 plain tubes
  • 1 mg Depot Synacthen (1 vial)



take 5 mL blood for cortisol
inject Synacthen 1 mg im


take further blood samples for cortisol at 60 min, 2, 4, 8 & 24 hours



95% CI cortisol responses

1 h

605-1265 nmol/L

2 h

750-1520 nmol/L

4 h

960-1650 nmol/L

8 h

1025-1600 nmol/L

24 h

609-1496 nmol/L

Sensitivity and Specificity

A gradual rise with a peak cortisol response at 4-8 hours occurs in normal subjects.

A response that rises gradually to a peak at 24 hours occurs in secondary adrenal failure i.e. due to pituitary failure or prolonged corticosteroid therapy. Some cases of long-standing adrenal atrophy will not respond even after 24 hours and will require several daily doses of depot Synacthen before an adrenal response is seen. The majority of these latter cases should be identifiable by measurement of plasma ACTH.


  • Galvao-Teles A, Burke CW, Fraser TR. Adrenal function tested with tetracosactrin depot. Lancet 1971;i:557-560.
  • Jenkins RC, Ross RJM. Protocols for common endocrine tests. In: Grossman A (ed). Clinical Endocrinology. Blackwells Science, Oxford. 2nd edit 1998:1117-1134.

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