Ten Years on: Safety of Short Synacthen Tests in Assessing Adrenocorticotropin Deficiency in Clinical Practice

Abstract

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.

Can basal cortisol measurement be an alternative to the insulin tolerance test in the assessment of the hypothalamic–pituitary–adrenal axis before and after pituitary surgery?

“…If serum cortisol is %100 nmol/l (3.6 mg/dl), HPA axis insufficiency is present (6,(22)(23)(24). If the serum cortisol level is R400 or 450 nmol/l (14.5-16 mg/dl), the HPA axis is thought to be sufficient (6,(23)(24)(25). The minimum cortisol levels which would allow us to predict adrenal insufficiency with 100% specifity in the very early (2nd and 3rd) postoperative days were found to be higher than the minimum cortisol levels found on the 6th day.…”

The diagnosis and investigation of adrenal insufficiency in adults

“…70 Some centres have observed a good correlation between synacthen and ITTs with false-negative rates of 3% (2 out of 69 who passed short synacthen test) in postpituitary surgery patients and a predictive value of 97%. 95 Others have found higher false-negative rates during testing, 75 particularly one week after surgery and it is generally accepted that the short synacthen test should not be used during the first 4 -6 weeks following pituitary surgery. 57,61,63,75,96 As discussed earlier, while basal cortisol values above 500 nmol/L are usually considered to be consistent with adequate adrenal reserve, in the first week following pituitary surgery, basal cortisol values above 393-450 nmol/L were recently demonstrated to correlate with normal cortisol responses to hypoglycaemia.…”

The short synacthen test may be more sensitive than the glucagon stimulation test in assessing the hypothalamic--pituitary--adrenal axis: a retrospective audit

“…Concern regarding test reliability and variability in interpretation of investigations due to gender, age and lack of standard assays is well reported. 1,2 Insulin-induced hypoglycaemia with the Insulin Tolerance Test (ITT) is considered the gold standard assessment of HPA integrity. 3 The Short Synacthen Test (SST) is a relatively simple, low-cost and well tolerated first line test of HPA despite concerns regarding accuracy.…”