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

Abstract

Context The normal cortisol response 30 or 60 min after cosyntropin (ACTH[1-24]) is considered ≥18 μg/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 ACTH stimulation testing with newer specific cortisol assays. Design 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 110 patients were evaluated. Using 18 μg/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 μg/dL. For 30 min values, new cutoffs were 14.6 μg/dL for Elecsys II, 14.8 μg/dL for Access, and 14.5 μg/dL for LC-MS/MS. Baseline cortisol <2 μg/dL was predictive of subnormal stimulated cortisol values. Conclusions To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14-15 μg/dL depending on the assay used (instead of the historical value of 18 μg/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.

Letter to the Editor From Powers Carson and Gronowski: “New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency After ACTH Stimulation Using Specific Cortisol Assays”

“…This resulted in a Deming regression with slope of 0.816 (0.768-0.864) and intercept of −0.208 (−0.965 to 0.550) with a correlation coefficient of 0.9846 and a standard error estimate of 1.253. Using this equation, a cutoff of 18 µg/dL with the Roche Cortisol I assay would equal 14.5 µg/dL on the Roche Cortisol II assay, supporting the findings of Javorsky et al [ 1 ].…”

“…In a recent paper by Javorsky et al [ 1 ], new cortisol cutoffs for cosyntropin stimulation testing to diagnose adrenal insufficiency were proposed for 2 immunoassays as well as a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method. The new cutoffs varied from 14 to 15 µg/dL and were based on comparisons of 110 subjects using the Elecsys Cortisol I assay with a cutoff of 18 µg/dL as the standard.…”

Latent Adrenal Insufficiency: From Concept to Diagnosis

“…This would potentially reduce overdiagnosis of AI. Additionally, a baseline cortisol less than 55 nmol/L successfully predicted abnormal response to stimulation test (56). A recent retrospective study conducted on 370 patients in Spain (58), confirmed need for sex-specific and assay-specific cutoff values when interpreting corticotropin test to reduce false positives and increase specificity.…”

“…Diagnostic cutoff values of serum cortisol depend on the assay used: in most immunoassays, 500 nmol/L is often used as the cutoff to establish diagnosis (6). However, newer monoclonal immunoassays such as the Elecsys ® Cortisol II from (56,57). This would potentially reduce overdiagnosis of AI.…”

Response to the Letter to the Editor From Jialal and Sood: “New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency After ACTH Stimulation Using Specific Cortisol Assays”

“…As pointed out by Drs. Jialal and Sood, the cosyntropin-stimulated cortisol cutoffs we provided in our report for the Beckman Access cortisol immunoassay are still valid [ 1 ].…”