The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitary-adrenal axis.
BACKGROUND
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
Our objective was to evaluate the long-term safety of the SST.


METHODS
We retrospectively evaluated the clinical outcome in 178 patients who achieved 30-min cortisol values in the lowest 15th percentile of normal healthy responses. Thirty patients were later excluded because of missing case notes (20 patients) or unsubstantiated pituitary pathology (10 patients). The remaining 148 patients were divided into two groups: group 1, patients with cortisol response between the 5th and 15th percentiles of normal response (551-635 nmol/liter, 98 patients); and group 2, patients with borderline response between the 2.5th and 5th percentiles (510-550 nmol/liter, 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). A total of 137 patients showed no clinical or biochemical evidence of adrenal insufficiency during follow-up. Of the remaining 11 patients, seven became hypoadrenal after 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.


CONCLUSIONS
The high-dose SST is safe for the purpose of excluding clinically significant secondary adrenal insufficiency and is indicated as the first line of investigation for this purpose.
Agha
Amar
A
Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. a.agha@qmul.ac.uk
Tomlinson
Jeremy W
JW
Clark
Penelope M
PM
Holder
Geoff
G
Stewart
Paul M
PM
D000236:Adenoma / Q000175:diagnosis / Q000601:surgery; D000293:Adolescent; D000309:Adrenal Insufficiency / Q000175:diagnosis; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004652:Empty Sella Syndrome / Q000175:diagnosis; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000627:therapeutic use; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007238:Infarction / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010900:Pituitary Diseases / Q000175:diagnosis; D010901:Pituitary Function Tests; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000601:surgery; D010912:Pituitary-Adrenal Function Tests; D011237:Predictive Value of Tests; D011247:Pregnancy; D012189:Retrospective Studies; D016896:Treatment Outcome
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone