ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis

Abstract

The diagnosis of adrenal insufficiency is clinically challenging and often requires ACTH stimulation tests. To determine the diagnostic accuracy of the high (250 mcg) and low (1 mcg) dose ACTH stimulation tests in the diagnosis of adrenal insufficiency. We searched 6 databases through February 2014. Pairs of independent reviewers selected studies and appraised the risk of bias. Diagnostic association measures were pooled across studies using a bivariate model. For secondary adrenal insufficiency, we included 30 studies enrolling 1,209 adults and 228 children. High and low dose ACTH stimulation tests had similar diagnostic accuracy in adults and children using different peak serum cortisol cut-offs. In general, both tests had low sensitivity and high specificity resulting in reasonable likelihood ratios for a positive test (Adults: High dose 9.1, Low dose 5.9; Children: High dose 43.5, Low dose 7.7), but a fairly suboptimal likelihood ratio for a negative test (Adults: High dose 0.39, Low dose 0.19; Children: High dose 0.65, Low dose 0.34). For primary adrenal insufficiency, we included 5 studies enrolling 100 patients. Data were only available to estimate the sensitivity of high dose ACTH stimulation test (92%; 95% CI: 81%–97%). Both high and low dose ACTH stimulation tests had similar diagnostic accuracy. Both tests are adequate to rule in, but not rule out, primary and secondary adrenal insufficiency. Our confidence in these estimates is low to moderate due to the likely risk of bias, heterogeneity and imprecision.