Dynamic testing of cortisol in consecutive patients with suspected adrenal disorders: a comparison of Elecsys Cortisol II and LC-MS/MS

The increased detection of adrenal incidentalomas and drug-induced adrenal insufficiency increases the demand for cortisol testing. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) and dynamic testing remain the gold standard, more expedient tools are needed. We compared the Elecsys Cortisol II immunoassay (ElecsysCort II) with LC-MS/MS during dynamic testing and evaluated the diagnostic performance of baseline cortisol cutoffs (0 min cortisol during a short Synacthen test). The study included 547 overnight dexamethasone suppression tests (44% abnormal), mainly performed in adrenal incidentaloma patients (69%), and 519 Synacthen tests (32% abnormal). ElecsysCort II slightly underestimated cortisol compared with LC-MS/MS with a Passing-Bablok regression of -3.20 (95% CI: -3.66 to -2.83) + 0.96X (95% CI: 0.96-0.97) and a mean relative difference of -8.22% (95% CI: -8.99% to -7.45%) by Bland-Altman, which was within the limits of acceptable bias based on biological variation. Agreement was not affected by glucocorticoid or estradiol intake. Compared with LC-MS/MS, ElecsysCort II demonstrated a specificity of 100%, sensitivity of 84%, positive predictive value of 99%, and negative predictive value of 86% for an abnormal overnight dexamethasone suppression test (480 min cortisol ≥50 nmol/L). For an abnormal Synacthen test (30 min cortisol <420 nmol/L), the measures were 95, 99, 89, and 100%, respectively. A baseline cortisol cutoff >300 nmol/L to rule out and <150 nmol/L to rule in adrenal insufficiency demonstrated a high specificity (>92%) and a positive predictive value (>87%). Our study supports the use of ElecsysCort II in general and baseline cortisol as a screening tool for adrenal insufficiency. The high proportion of abnormal overnight dexamethasone suppression tests among incidentaloma patients warrants further research.