Abstract
PurposeThe current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays.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.MethodsWe 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.ResultsMean 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.ConclusionsThe 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.
Highlights
Adrenal insufficiency (AI) is a potentially life-threatening medical condition in which cortisol secretion is impaired because of adrenal or pituitary failure
Diagnosis is mainly based on measuring cortisol concentrations after a stimulation test: the standard dose (250 μg) corticotropin (1–24 ACTH) test (SDCT) represents the gold standard dynamic test for PAI, while the insulin tolerance test (ITT) is the gold standard if SAI is suspected [1,2,3,4,5]
Overall mean cortisol concentrations measured with R1, R2, and LC-MS/MS were, respectively, 411 ± 177 (14.9 ± 6.4), 287 ± 119 (10.4 ± 4.3), and 295 ± 119 (10.7 ± 4.3) nmol/L in basal conditions; 704 ± 204 (25.5 ± 7.4), 480 ± 132 (17.4 ± 4.8), and 500 ± 132 (18.1 ± 4.8) nmol/L at 30 min; and 737 ± 301 (26.7 ± 10.9), 502 ± 196 (18.1 ± 7.1), and 519 ± 201 (18.8 ± 7.3) nmol/L at 60 min after the ACTH test
Summary
Adrenal insufficiency (AI) is a potentially life-threatening medical condition in which cortisol secretion is impaired because of adrenal (primary adrenal insufficiency, PAI) or pituitary failure (secondary adrenal insufficiency, SAI). Diagnosis is mainly based on measuring cortisol concentrations after a stimulation test: the standard dose (250 μg) corticotropin (1–24 ACTH) test (SDCT) represents the gold standard dynamic test for PAI, while the insulin tolerance test (ITT) is the gold standard if SAI is suspected [1,2,3,4,5]. Using the R2 assay, new peak cortisol cut-offs as low as 375 and 351 nmol/L (13.6 and 12.7 μg/dL, respectively) have been proposed for the diagnosis of AI by two preliminary studies [17, 18]. These values are notably lower than the cut-offs suggested by the current guidelines and, need to be updated. This issue is crucial for patients because of the diagnostic and therapeutic implications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
