Utility of the low-dose short Synacthen test in diagnosis of adrenal insufficiency in outpatients with nonspecific symptoms

Short Synacthen tests are used to diagnose primary and secondary adrenal insufficiency. The standard test uses supraphysiological adrenocorticotropic hormone (250 μg). The low-dose test (1 μg) was proposed to be more sensitive. In outpatients with nonspecific symptoms referred for exclusion of adrenal insufficiency, we assessed whether the low-dose test was an appropriate initial investigation. Results of 233 low-dose tests were obtained from pathology database 2007-2009. Clinical data were available for 169 patients: 37 taking glucocorticoids or with known pituitary/adrenal disease were excluded. Among the remaining 132 patients, 26% failed using stimulated cortisol ≥500 nmol/L and 45% failed at ≥550 nmol/L. These rates of apparent adrenal insufficiency are ~50 fold above expected. In conclusion, the low-dose test, using conventional criteria for normality, is abnormal in a large proportion of patients with nonspecific symptoms. Until criteria for normal cortisol response to low-dose Synacthen are clarified, alternative tests of adrenal function are advised in this clinical setting.