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. doi: 10.1210/jc.2002-020969.


Since 1988, when a retrospective study of patients attending this unit was published, we have advocated the use of the short synacthen test (SST) as the primary screening investigation to detect ACTH deficiency. However, others have published comparisons of SST and insulin tolerance tests that suggest a significant false negative rate with SST, leading to concern that some patients who pass the SST are in danger from the clinical consequences of ACTH deficiency. To address this, we audited biochemical results and clinical outcome in 63 patients who did not have ACTH deficiency detected (i.e. who passed the test) by SST after pituitary surgery. Twelve of the 63 patients who passed a SST after pituitary surgery became ACTH-deficient later as diagnosed by SST: 4 within the first year, 2 of whom had received postoperative radiotherapy (3 had symptoms of tiredness and 1 was admitted to the hospital with a viral infection); 8 in yr 3-5, 7 of whom had received postoperative radiotherapy (all had either no symptoms or symptoms of tiredness alone). Thus, the predictive value of the SST in excluding ACTH deficiency is approximately 97% (2 of 63 patients who initially passed the SST were found to be ACTH-deficient within 12 months without having received postoperative radiotherapy). Only 1 patient was ill enough to require hospital admission. Setting the risk of false negatives with SST against the morbidity and manpower implications associated with insulin tolerance tests, SST remains the primary screening test for ACTH deficiency in our practice. However, a high index of clinical suspicion to detect false negative results must be maintained.

Publication types

  • Case Reports

MeSH terms

  • Acromegaly / surgery
  • Adenoma / surgery
  • Adolescent
  • Adrenocorticotropic Hormone / deficiency*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cosyntropin*
  • Craniopharyngioma / surgery
  • False Negative Reactions
  • Female
  • Humans
  • Hydrocortisone / blood
  • Insulin
  • Male
  • Middle Aged
  • Pituitary Gland / surgery
  • Pituitary Neoplasms / surgery
  • Prolactinoma / surgery
  • Retrospective Studies
  • Sensitivity and Specificity


  • Insulin
  • Cosyntropin
  • adrenocorticotropin zinc
  • Adrenocorticotropic Hormone
  • Hydrocortisone