Reference Curves for Pediatric Endocrinology: Leveraging Biomarker Z-Scores for Clinical Classifications.


Journal

The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362

Informations de publication

Date de publication:
16 06 2022
Historique:
received: 17 12 2021
pubmed: 18 3 2022
medline: 22 6 2022
entrez: 17 3 2022
Statut: ppublish

Résumé

Hormone reference intervals in pediatric endocrinology are traditionally partitioned by age and lack the framework for benchmarking individual blood test results as normalized z-scores and plotting sequential measurements onto a chart. Reference curve modeling is applicable to endocrine variables and represents a standardized method to account for variation with gender and age. We aimed to establish gender-specific biomarker reference curves for clinical use and benchmark associations between hormones, pubertal phenotype, and body mass index (BMI). Using cross-sectional population sample data from 2139 healthy Norwegian children and adolescents, we analyzed the pubertal status, ultrasound measures of glandular breast tissue (girls) and testicular volume (boys), BMI, and laboratory measurements of 17 clinical biomarkers modeled using the established "LMS" growth chart algorithm in R. Reference curves for puberty hormones and pertinent biomarkers were modeled to adjust for age and gender. Z-score equivalents of biomarker levels and anthropometric measurements were compiled in a comprehensive beta coefficient matrix for each gender. Excerpted from this analysis and independently of age, BMI was positively associated with female glandular breast volume (β = 0.5, P < 0.001) and leptin (β = 0.6, P < 0.001), and inversely correlated with serum levels of sex hormone-binding globulin (SHBG) (β = -0.4, P < 0.001). Biomarker z-score profiles differed significantly between cohort subgroups stratified by puberty phenotype and BMI weight class. Biomarker reference curves and corresponding z-scores provide an intuitive framework for clinical implementation in pediatric endocrinology and facilitate the application of machine learning classification and covariate precision medicine for pediatric patients.

Identifiants

pubmed: 35299255
pii: 6550279
doi: 10.1210/clinem/dgac155
pmc: PMC9202734
doi:

Substances chimiques

Biomarkers 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2004-2015

Subventions

Organisme : Haukeland University Hospital

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

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Auteurs

Andre Madsen (A)

Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Bjørg Almås (B)

Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Ingvild S Bruserud (IS)

Faculty of Health, VID Specialized University, Bergen, Norway.
Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.

Ninnie Helen Bakken Oehme (NHB)

Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.

Christopher Sivert Nielsen (CS)

Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway.

Mathieu Roelants (M)

Environment and Health, Department of Public Health and Primary Care, KU Leuven, University of Leuven, Leuven, Belgium.

Thomas Hundhausen (T)

Department of Medical Biochemistry, Southern Norway Hospital Trust, Kristiansand, Norway.
Department of Natural Sciences, University of Agder, Kristiansand, Norway.

Marie Lindhardt Ljubicic (ML)

Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark.

Robert Bjerknes (R)

Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.

Gunnar Mellgren (G)

Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.
Mohn Nutrition Research Laboratory, University of Bergen, Bergen, Norway.

Jørn V Sagen (JV)

Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.

Pétur B Juliusson (PB)

Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway.

Kristin Viste (K)

Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

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