Reference curves for pediatric endocrinology: leveraging biomarker z-scores for clinical classifications
AuthorMadsen, Andre; Almås, Bjørg; Bruserud, Ingvild Særvold; Oehme, Ninnie Helen Bakken; Nielsen, Christopher Sivert; Roelants, Mathieu; Hundhausen, Thomas Eckhard; Ljubicic, Marie Lindhardt; Bjerknes, Robert; Mellgren, Gunnar; Sagen, Jørn V.; Juliusson, Pétur Benedikt; Viste, Kristin
Objective: We aimed to establish gender-specifc biomarker reference curves for clinical use and benchmark associations between hormones, pubertal phenotype, and body mass index (BMI).
Methods: 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.
Results: 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 coeffcient 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 profles differed signifcantly between cohort subgroups stratifed by puberty phenotype and BMI weight class.