ArticleThe Journal of clinical endocrinology and metabolism2022
Reference Curves for Pediatric Endocrinology: Leveraging Biomarker Z-Scores for Clinical Classifications.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Pubertal Testicular Function in Childhood Cancer Survivors and Future Fertility.JAMA network open · 2026Article
- Trunk Muscle Performance, Spinal Alignment, and Postural Profiles in 9-11-Year-Old Children Participating in Intensively Organized Sport Assessed with Non-Radiographic Tools.Sports (Basel, Switzerland) · 2026Article
- Per- and Polyfluoroalkyl Substance Exposure Associated with Later Puberty in Norwegian Girls: Data from the Bergen Growth Study 2.Environment & health (Washington, D.C.) · 2026Article
- Associations Between Weight-Related Measurements and Pubertal Markers in Norwegian Girls: The Bergen Growth Study 2.Journal of the Endocrine Society · 2025Article
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 2025Review
- Transition of clinical biomarker status from childhood into adolescence-A prospective study in children from eight European countries.PloS one · 2025Article
- Exposure to Per- and Polyfluoroalkyl Substances and Timing of Puberty in Norwegian Boys: Data from the Bergen Growth Study 2.Environmental science & technology · 2024Article
- Biochemical identification of prepubertal boys with Klinefelter syndrome by combined reproductive hormone profiling using machine learning.Endocrine connections · 2023Article
- The Beauty of Age-dependent Standardization in Pediatric Endocrine Research and Practice.The Journal of clinical endocrinology and metabolism · 2022Article
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
contextHormone 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.
objectiveWe aimed to establish gender-specific biomarker reference curves for clinical use and benchmark associations between hormones, pubertal phenotype, and body mass index (BMI).
methodsUsing 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.
resultsReference 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.
conclusionBiomarker 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.
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