1. The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS
- Author
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Maria Ræder, Gunnar Mellgren, Kristian Løvås, Marianne Øksnes, Per Medbøe Thorsby, Grethe Å Ueland, Ralf Kellmann, Jørn V. Sagen, Sandra Rinne Dahl, Per Dahlqvist, Eystein S. Husebye, Hrafnkell Thordarson, and Paal Methlie
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Urology ,030209 endocrinology & metabolism ,Reference range ,Biochemistry ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Reference Values ,Tandem Mass Spectrometry ,Internal medicine ,Cosyntropin ,Lc ms ms ,medicine ,Adrenal insufficiency ,Humans ,Congenital adrenal hyperplasia ,Cosyntropin test ,Aged ,Aged, 80 and over ,Adrenal Hyperplasia, Congenital ,business.industry ,17-alpha-Hydroxyprogesterone ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,New normal ,030104 developmental biology ,Reference values ,Female ,business ,Adrenal Insufficiency ,Chromatography, Liquid - Abstract
The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges.The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays.Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile.Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively.LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.
- Published
- 2018
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