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Hair glucocorticoids as biomarker for endogenous Cushing's syndrome: validation in two independent cohorts


Savas, Mesut; Wester, Vincent L; de Rijke, Yolanda B; Rubinstein, German; Zopp, Stephanie; Dorst, Kristien; van den Berg, Sjoerd A A; Beuschlein, Felix; Feelders, Richard A; Reincke, Martin; van Rossum, Elisabeth F C (2019). Hair glucocorticoids as biomarker for endogenous Cushing's syndrome: validation in two independent cohorts. Neuroendocrinology, 109(2):171-178.

Abstract

Background/Aims: The current diagnostic workup of Cushing’s syndrome (CS) requires various tests which only capture short-term cortisol exposure, whereas patients with endogenous CS generally have elevated long-term cortisol levels. Scalp hair assessment has emerged as a convenient test in capturing glucocorticoid concentrations over long periods of time. The aim of this multicenter, multinational, prospective, case-control study was to evaluate the diagnostic efficacy of scalp hair glucocorticoids in screening of endogenous CS.
Methods: We assessed the diagnostic performances of hair cortisol (HairF), hair cortisone (HairE), and sum of both (sumHairF+E), as measured by state-of-the-art LC-MS/MS technique, in untreated patients with confirmed endogenous CS (n=89), and community controls (n=295) from the population-based Lifelines cohort study.
Results: Both glucocorticoids were significantly elevated in CS patients when compared to controls. High diagnostic efficacy was found for HairF (area under the curve (AUC), 0.87 [95% CI, 0.83 to 0.92]), HairE (0.93 [0.89 to 0.96]) and sumHairF+E (0.92 [0.88 to 0.96]; all P<.001). Participants were accurately classified at optimal cut-off threshold in 86% of cases (81% sensitivity, 88% specificity, 94% negative predictive value (NPV)) for HairF, in 90% of cases (87% sensitivity, 90% specificity, 96% NPV) for HairE, and 87% of cases (86% sensitivity, 88% specificity, 95% NPV) for the sum. HairE was shown to be most accurate in differentiating CS patients from controls.
Conclusion: Scalp hair glucocorticoids, especially hair cortisone, can be seen as a promising biomarker in screening of CS. Its convenience in collection and workup additionally makes this feasible for first-line screening

Abstract

Background/Aims: The current diagnostic workup of Cushing’s syndrome (CS) requires various tests which only capture short-term cortisol exposure, whereas patients with endogenous CS generally have elevated long-term cortisol levels. Scalp hair assessment has emerged as a convenient test in capturing glucocorticoid concentrations over long periods of time. The aim of this multicenter, multinational, prospective, case-control study was to evaluate the diagnostic efficacy of scalp hair glucocorticoids in screening of endogenous CS.
Methods: We assessed the diagnostic performances of hair cortisol (HairF), hair cortisone (HairE), and sum of both (sumHairF+E), as measured by state-of-the-art LC-MS/MS technique, in untreated patients with confirmed endogenous CS (n=89), and community controls (n=295) from the population-based Lifelines cohort study.
Results: Both glucocorticoids were significantly elevated in CS patients when compared to controls. High diagnostic efficacy was found for HairF (area under the curve (AUC), 0.87 [95% CI, 0.83 to 0.92]), HairE (0.93 [0.89 to 0.96]) and sumHairF+E (0.92 [0.88 to 0.96]; all P<.001). Participants were accurately classified at optimal cut-off threshold in 86% of cases (81% sensitivity, 88% specificity, 94% negative predictive value (NPV)) for HairF, in 90% of cases (87% sensitivity, 90% specificity, 96% NPV) for HairE, and 87% of cases (86% sensitivity, 88% specificity, 95% NPV) for the sum. HairE was shown to be most accurate in differentiating CS patients from controls.
Conclusion: Scalp hair glucocorticoids, especially hair cortisone, can be seen as a promising biomarker in screening of CS. Its convenience in collection and workup additionally makes this feasible for first-line screening

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Endocrinology
Life Sciences > Endocrine and Autonomic Systems
Life Sciences > Cellular and Molecular Neuroscience
Language:English
Date:1 January 2019
Deposited On:18 Mar 2019 11:23
Last Modified:29 Jul 2020 10:23
Publisher:Karger
ISSN:0028-3835
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1159/000498886
PubMed ID:30759443

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