Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience
PURPOSE:The current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test.METHODS:We enrolled 30 patients (age 47?±?21?years) referred to undergo the ACTH test (1 or 250?μg). Cortisol was measured at 0, 30, and 60?min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations ?500?nmol/L.RESULTS:Mean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411?±?177, 287?±?119, and 295?±?119?nmol/L; at 30?min, 704?±?204, 480?±?132, and 500?±?132?nmol/L; at 60?min, 737?±?301, 502?±?196, and 519?±?201?nmol/L, p?≤?0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500?nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 ( ?140%). Based on the correlation between R1 and R2, the threshold of 500?nmol/L became 351?nmol/L (12.7?μg/dL) when cortisol was measured with R2, and 368?nmol/L (13.3?μg/dL) with LC-MS/MS.CONCLUSIONS:The use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted.
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