Low-dose (1 mu g) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo-pituitary-adrenal axis function: sensitivity, specificity and accuracy in comparison with the high-dose (250 mu g) test

OBJECTIVE We have shown previously that in contrast to the standard high-do se 250-mu g ACTH test, a low-dose l-pg ACTH stimulation test correctly iden tified all patients with pituitary disease who had impaired hypothalamo-pit uitary-adrenal (HPA) function. In this study we further compared the perfor mances of these two tests as screening procedures for possible HPA impairme nt. DESIGN A comparison of the 1-mu g and the 250-mu g ACTH stimulation tests i n healthy controls and in patients with pituitary disease whose HPA axis st atus was characterized formally by a gold standard test. SUBJECTS A total of 89 subjects were investigated: 27 healthy normal contro ls, 43 patients with pituitary disease and normal HPA function, and 19 pati ents with various pituitary diseases and impaired HPA function. MEASURES Ail 89 subjects underwent stimulation with 1 mu g ACTH; 80 also un derwent the high-dose 250-mu g ACTH test. A receiver operating characterist ic analysis (ROC) was performed to compare the tests. RESULTS Using a stimulated cortisol >500 nmol/l as the criterion for a norm al response, the 1-mu g ACTH stimulation identified 18 of the 19 subjects w ith impaired HPA function (94.7% sensitivity with a likelihood ratio of 0.0 588 for a negative test). In contrast, 15/16 passed the high-dose test (a 6 .2% sensitivity with a likelihood ratio of 0.875 for a negative test), All normal controls, and 36/43 patients with preserved HPA function, passed the 1-mu g ACTH test (90% specificity). This degree of accuracy was unrivalled by the high dose test at all the cut-off levels considered. CONCLUSIONS More sensitive and accurate, the low-dose 1-mu g ACTH test is a s simple and safe as the standard 250-mu g test. We suggest it should repla ce it in screening for adrenal insufficiency.