Context: The high dose short Synacthen (corticotropin) test (SST) is widely used to investigate suspected secondary adrenal insufficiency but concern remains about falsely reassuring results.

Objective: To evaluate the long-term safety of the SST

Method: We retrospectively evaluated the clinical outcome in 178 patients who achieved 30-minute cortisol values in the lowest 15^th percentile of normal healthy responses.30 patients were later excluded because of missing case notes (20 patients) or unsubstantiated pituitary pathology (10 patients). The remaining 148 patients were divided into 2 groups; group 1: patients with cortisol response between the 5^th and15^th percentile of normal response (551-635 nmol/l, 98 patients), group 2: patients with borderline response between the 2.5^th and 5^th percentile (510-550 nmol/l, 50 patients). Patients did not receive routine glucocorticoid therapy but those in group 2 were advised to take hydrocortisone in case of intercurrent illness

Results: The median follow-up period from the initial SST was 4.2 yr (range 4 months to 7 yr). 137 patients showed no clinical or biochemical evidence of adrenal insufficiency during follow-up. Of the remaining 11 patients, 7 became hypoadrenal following subsequent pituitary surgery or radiotherapy, one patient in group 1 developed adrenal insufficiency at 2 yr and one patient in group 2 developed adrenal insufficiency at 6 months. The other two patients who were in group 2 had clinical diagnostic uncertainty.

Conclusion: The high-dose SST is safe for the purpose of excluding clinically significant secondary adrenal insufficiency and is indicated as the first line investigation for this purpose.