PSAT085 Monoclonal Cortisol Immunoassay Cut Off Point to Diagnose Adrenal Insufficiency (AI)

OBJECTIVE: Adrenal Insufficiency (AI) is diagnosed when the peak cortisol level after a cosyntropin stimulation test is <18 mg/dL using a standard reference (e.g. polyclonal antibody (pAb) immunoassay). However, in most laboratories the polyclonal assay is being replaced by a specific monoclonal antibody (mAb) immunoassay which yields lower cortisol levels, leading to the over diagnosis of AI and unnecessary steroid use. METHODS/STUDY POPULATION: We obtained blood samples from 36 patients undergoing 1 mcg cosyntropin stimulation tests for diagnosis of AI. Samples were analyzed using pAb immunoassay (Abbott Architect Cortisol), mAb immunoassay (Roche Elecsys Cortisol II), and mass spectrometry (MS). AI was diagnosed if serum cortisol level was <18 using the pAb immunoassay. Measurements by MS and mAb immunoassay were individually used in simple logistic regression models to predict AI. For each model, we calculated a cortisol level corresponding to a 50% probability (median) of AI and used the delta method to determine the standard error and 95% confidence interval of the median. We used receiver operator characteristic (ROC) curve, area under the curve, sensitivity, and specificity to evaluate the potential of the median values as thresholds for each predictor. RESULTS: The ROC curve model indicated an area under the curve of 0.997 with a median value of 11.2 mcg/dL for the mAb immunoassay. This provides a sensitivity of 95%, specificity of 95%, positive predictive value of 95%, and negative predictive value of 94%. This new value has a Kappa coefficient of 0.89 when compared to the pAb immunoassay. When using all the data points throughout the stimulation test, data showed a mean difference in cortisol level between the mAb immunoassay and the pAb immunoassay of 5.12 mcg/dL (p-value <0.01) at any point during the test. DISCUSSION/SIGNIFICANCE: New and highly specific mAb immunoassays are being used more widely but yield lower cortisol results. This reflects the need for further studies to determine new cut off points for highly specific cortisol immunoassays. A cut off level of 11.2 mcg/dL for the mAb immunoassay would provide a sensitivity of 95% and specificity of 95%. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.