The high dose short Synacthen (corticotropin) test (SST) is widely used to investigate suspected secondary adrenal insufficiency but concern remains about falsely reassuring results with potentially serious clinical consequences.
In order to evaluate the long-term safety of the SST, we retrospectively evaluated the clinical outcome in 178 patients who achieved 30-minute cortisol values in the lowest 15th percentile of normal healthy responses. This subgroup was selected because it is considered to be at particular risk of falsely reassuring results. 30 patients were later excluded because of missing case notes or unsubstantiated pituitary pathology. Detailed case notes assessment was performed for 148 pituitary patients. Patients were divided into 2 groups; group 1: patients with cortisol response between the 5th and15th percentile of normal response (551635 nmol/l, 98 patients), group 2: patients with borderline response between the 2.5th and 5th percentile (510550 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.
The median follow-up period from the initial SST was 4.2 years (range 4 months to 7 years). 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 years 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.
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.