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The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS

The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS

Grethe Å Ueland, Paal Methlie, Marianne Øksnes, Hrafnkell B Thordarson, Jørn Sagen, Ralf Kellmann, Gunnar Mellgren, Maria Ræder, Per Dahlqvist, Sandra R Dahl, Per M Thorsby, Kristian Løvås, Eystein S Husebye

J Clin Endocrinol Metab. 2018 Apr 1;103(4):1696-1703.

PMID: 29452421

Abstract:

Background:
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.
Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP16960160	Cosyntropin acetate		16960-16-0 (free base)	Price

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