Peak Serum Cortisol Cutoffs to Diagnose Adrenal Insufficiency Across Different Cortisol Assays in Children.

OBJECTIVE: Current peak serum cortisol cutoffs for the diagnosis of adrenal insufficiency (AI) after Cosyntropin stimulation have been established using polyclonal antibody (pAb) immunoassays. However, new and highly specific cortisol monoclonal antibody (mAb) immunoassays are being used more widely which can potentially yield higher false positive rates. Thus, this study aims to redefine the biochemical diagnostic cutoff points for AI in children when using a highly specific cortisol mAb immunoassay and liquid chromatography tandem mass spectrometry (LC/MS) to avoid unnecessary steroid use.

METHODS: Cortisol levels from 36 children undergoing 1 mcg Cosyntropin stimulation tests to rule out AI were measured using polyclonal antibody (pAb) immunoassay (Roche Elecsys Cortisol I), mAB immunoassay (Roche Elecsys Cortisol II), and LC/MS. Logistic regression was used to predict AI using the pAB as the reference standard. A receiver operator characteristic curve (ROC), area under the curve (AUC), sensitivity, specificity, and kappa agreement were also calculated.

RESULTS: Using a peak serum cortisol cutoff value of 12.5 μg/dL for the mAb immunoassay provides a 99% sensitivity and 94% specificity for diagnosing AI, when compared to the historical pAb immunoassay cutoff of 18 μg/dL (AUC= 0.997). Likewise, a cutoff of value of 14 μg/dL using the LC/MS, provides a 99% sensitivity and 88% specificity when compared to the pAb immunoassay (AUC=0.995).

CONCLUSION: To prevent overdiagnosis of AI in children undergoing 1 mcg Cosyntropin stimulation test, our data support using a new peak serum cortisol cutoff of 12.5 μg/dL and 14 μg/dL to diagnose AI when using mAb immunoassays and LC/MS in children, respectively.