Agha A et al. (2006) The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamicpituitary-adrenal axis. J Clin Endocrinol Metab 91: 43–47

The high-dose short Synacthen® (Alliance Pharmaceuticals Ltd., Chippenham, UK) (corticotropin) test (SST) is often used as an alternative to the insulin tolerance (hypoglycemia) test (ITT) in the investigation of secondary adrenal insufficiency, but questions have been raised regarding the SST's false-negative rate, particularly at the lower end (18–23 μg/dl) of the normal range of values. In order to investigate this concern, a British team has retrospectively followed patients who scored in the lowest 15th centile (≤22.7 μg/dl) of normal (healthy) responses to the SST, and who did not receive replacement glucocorticoid therapy.

Final analysis included 148 patients (94 women), who were followed up for a median of 4.2 years (range 4 months to 7 years). When clinical outcome was used as the gold standard, the SST was found to have a false-negative rate below 1%.

This result is similar to that of the only previous study to evaluate the SST using clinical outcome as a reference. Most studies have compared the SST with the ITT, and have variously reported the SST's sensitivity to be 65–100%; however, the ITT has been known to give false-positive results, so a poor response to the ITT does not always prove adrenal insufficiency. They recommend that the SST should continue to be used as a first-line diagnostic tool for secondary adrenal insufficiency; however, like all tests, the results should be interpreted in the light of the whole clinical picture.