New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays

Context: The normal cortisol response 30 or 60 minutes after cosyntropin (ACTH([1-24])) is considered to be >= 18 mu g/dL (500 nmol/L). This threshold is based on older serum cortisol assays. Specific monoclonal antibody immunoassays or LC-MS/MS may have lower thresholds for a normal response. Objective: To calculate serum cortisol cutoff values for adrenocorticotropic hormone (ACTH) stimulation testing with newer specific cortisol assays. Methods: Retrospective analysis of ACTH stimulation tests performed in ambulatory and hospitalized patients suspected of adrenal insufficiency (AI). Serum samples were assayed for cortisol in parallel using Elecsys I and Elecsys II immunoassays, and when volume was available, by Access immunoassay and LC-MS/MS. Results: A total of 110 patients were evaluated. Using 18 mu g/dL as the cortisol cutoff after ACTH stimulation, 14.5%, 29%, 22.4%, and 32% of patients had a biochemical diagnosis of AI using the Elecsys I, Elecsys II, Access, and LC-MS/MS assays, respectively. Deming regressions of serum cortisol were used to calculate new cortisol cutoffs based on the Elecsys I cutoff of 18 mu g/dL. For 30-minute values, new cutoffs were 14.6 mu g/dL for Elecsys II, 14.8 mu g/dL for Access, and 14.5 mu g/dL for LC-MS/MS. Baseline cortisol <2 mu g/dL was predictive of subnormal stimulated cortisol values. Conclusion: To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14 to 15 mu g/dL depending on the assay used (instead of the historical value of 18 mu g/dL with older polyclonal antibody assays). Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for AI.