SAT-438 - Re-Assessment of Diagnostic Cortisol Values for Adrenal Insufficiency using A Highly Specific Cortisol Assay

Objective

Accurate diagnosis of adrenal insufficiency (AI) is critical as delayed diagnosis can be fatal, and misdiagnosis leads to unnecessary chronic glucocorticoid exposure. The 250 µg cosyntropin stimulation test (CST) is the preferred diagnostic test, with traditional cortisol cut-offs of < 18-20 µg/dL derived from older polyclonal antibody (Ab) assays. Newer monoclonal Ab assays yield lower cortisol values, raising concern that historical thresholds may overdiagnose AI. We hypothesized that the diagnostic cortisol threshold for AI with the CST is lower than 18 µg/dL with the Abbott Alinity (Alinity) assay.



Methods

In this prospective, cross-sectional study, CSTs were performed in healthy volunteers (HV; n = 16), patients with suspected AI (SAI; n = 20), and patients with known AI (KAI; n = 8). The primary aim was to define the optimal Alinity-specific stimulated cortisol thresholds for AI diagnosis using receiver operating characteristic analysis, which were then applied to the SAI cohort to assess diagnostic performance. Final AI status in SAI patients was assigned by expert endocrinologists. Secondary aims included identifying morning (AM) baseline cortisol threshold to exclude AI and assessing agreement between the Alinity and Roche Elecsys Cortisol II assays using Bland-Altman and Pearson correlation analyses.



Results

For stimulated cortisol, the Alinity assay showed an AUC of 1.00, with optimal cutoffs of 12.95 µg/dL (95% CI, 10.55-13.55) at 30 minutes and 15 µg/dL (95% CI, 12.35-16.15) at 60 minutes, each yielding 100% sensitivity and 100% specificity. Application of these thresholds to the SAI group yielded sensitivities and specificities of 83.3% and 100% at 30 minutes, and 75% and 100% at 60 minutes, respectively.

For AM baseline cortisol, the Alinity assay demonstrated an AUC of 0.992 (95% CI, 0.971-1), with an optimal cutoff of 6.6 µg/dL (95% CI, 2.85-7.4), yielding 100% sensitivity and 93.8% specificity. Application of this threshold to the SAI group yielded 83.3% sensitivity and 75% specificity.

Bland-Altman analysis comparing the Alinity and Roche assays in patients with confirmed AI (n = 20), showed a mean bias of 0.2 µg/dL (limits –1.09 to 1.5). In patients with confirmed absence of AI (n = 24), the mean bias was –0.43 µg/dL (limits –3.57 to 2.71). Pearson correlation analysis showed R2 = 0.9 in patients with and without AI.



Conclusion

The Alinity assay has high diagnostic performance and strong concordance with the Roche Elecsys Cortisol II assay. A 60-minute stimulated cortisol threshold of 15 µg/dL may be appropriate for excluding AI using Alinity. In low-risk patients, an AM baseline cortisol >6.6 µg/dL may obviate the need for CST. These findings support the use of lower monoclonal assay-specific CST thresholds and suggest that Roche-derived cutoffs may be applicable to Alinity assay, noting that higher thresholds favor sensitivity over specificity.

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