Hair Glucocorticoids as a Biomarker for Endogenous Cushing's Syndrome: Validation in Two Independent Cohorts.


Journal

Neuroendocrinology
ISSN: 1423-0194
Titre abrégé: Neuroendocrinology
Pays: Switzerland
ID NLM: 0035665

Informations de publication

Date de publication:
2019
Historique:
received: 31 10 2018
accepted: 12 02 2019
pubmed: 14 2 2019
medline: 2 6 2020
entrez: 14 2 2019
Statut: ppublish

Résumé

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 cortisol levels over longer periods of time. 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. We assessed the diagnostic performances of hair cortisol (HairF), hair cortisone (HairE), and the sum of both (sumHairF+E), as measured by a state-of-the-art LC-MS/MS technique, in untreated patients with confirmed endogenous CS (n = 89) as well as in community controls (n = 295) from the population-based Lifelines cohort study. Both glucocorticoids were significantly elevated in CS patients when compared to controls. A high diagnostic efficacy was found for HairF (area under the curve 0.87 [95% CI: 0.83-0.92]), HairE (0.93 [0.89-0.96]), and sumHairF+E (0.92 [0.88-0.96]) (all p < 0.001). The participants were accurately classified at the optimal cutoff threshold in 86% of the cases (81% sensitivity, 88% specificity, and 94% negative predictive value [NPV]) by HairF, in 90% of the cases (87% sensitivity, 90% specificity, and 96% NPV) by HairE, and in 87% of the cases (86% sensitivity, 88% specificity, and 95% NPV) by the sumHairF+E. HairE was shown to be the most accurate in differentiating CS patients from controls. Scalp hair glucocorticoids, especially hair cortisone, can be seen as a promising biomarker in screening for CS. Its convenience in collection and workup additionally makes it feasible for first-line screening.

Sections du résumé

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 cortisol levels over longer periods of time. 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 the sum of both (sumHairF+E), as measured by a state-of-the-art LC-MS/MS technique, in untreated patients with confirmed endogenous CS (n = 89) as well as in community controls (n = 295) from the population-based Lifelines cohort study.
RESULTS
Both glucocorticoids were significantly elevated in CS patients when compared to controls. A high diagnostic efficacy was found for HairF (area under the curve 0.87 [95% CI: 0.83-0.92]), HairE (0.93 [0.89-0.96]), and sumHairF+E (0.92 [0.88-0.96]) (all p < 0.001). The participants were accurately classified at the optimal cutoff threshold in 86% of the cases (81% sensitivity, 88% specificity, and 94% negative predictive value [NPV]) by HairF, in 90% of the cases (87% sensitivity, 90% specificity, and 96% NPV) by HairE, and in 87% of the cases (86% sensitivity, 88% specificity, and 95% NPV) by the sumHairF+E. HairE was shown to be the most accurate in differentiating CS patients from controls.
CONCLUSION
Scalp hair glucocorticoids, especially hair cortisone, can be seen as a promising biomarker in screening for CS. Its convenience in collection and workup additionally makes it feasible for first-line screening.

Identifiants

pubmed: 30759443
pii: 000498886
doi: 10.1159/000498886
doi:

Substances chimiques

Biomarkers 0
Glucocorticoids 0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

171-178

Informations de copyright

© 2019 The Author(s) Published by S. Karger AG, Basel.

Auteurs

Mesut Savas (M)

Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Vincent L Wester (VL)

Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Yolanda B de Rijke (YB)

Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

German Rubinstein (G)

Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany.

Stephanie Zopp (S)

Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany.

Kristien Dorst (K)

Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Sjoerd A A van den Berg (SAA)

Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Felix Beuschlein (F)

Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany.
Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitäts-Spital Zürich, Zurich, Switzerland.

Richard A Feelders (RA)

Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Martin Reincke (M)

Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany.

Elisabeth F C van Rossum (EFC)

Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, e.vanrossum@erasmusmc.nl.
Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, e.vanrossum@erasmusmc.nl.

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