Abstract
Abstract Objectives We established reference intervals for serum concentrations of hormones from healthy pediatric subjects and investigated their associations with gender, body mass index (BMI), puberty and oral contraceptives (oC). Methods We calculated reference intervals for the thyroid parameters thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and calcitonin (Ct); the bone markers osteocalcin, procolagen type 1 N-propeptide, and carboxy-terminal cross-linking telopeptide of type 1 collagen; the calciotropic hormones 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone and the steroids cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, dehydroepiandrosterone sulfate and aldosterone. Up to 10,002 blood serum samples from 3,229 healthy children and adolescents (age interval: 3 months to 20 years) were measured. To investigate the associations between the hormone levels with age, sex, weight status and the role of puberty-based changes, the measurement and BMI values were transformed into standard deviation scores. Results Most of the hormones depended on age- and gender. Puberty was linked to a, in part, temporary decrease in TSH, FT3 (for females), FT4, Ct, cortisol (for girls) and aldosterone (for boys) and peak in the bone marker and calciotropic hormones (excluding 25(OH)D) and nearly all remaining steroids. BMI had effects on the thyroid, bone, and calciotropic parameters, whereas oC led to increased cortisol, suppressed progesterone and estradiol values. Conclusions Age- and gender-specific reference intervals are essential for the interpretation of pediatric patients’ hormone measurements. Influencing factors as puberty, BMI, or oC should be taken into consideration for diagnosis and treatment monitoring.
Highlights
Relevant reference intervals are a mandatory precondition for the interpretation of endocrine biomarker measurements
To investigate the associations between the hormone levels with age, sex, weight status and the role of puberty-based changes, the measurement and body mass index (BMI) values were transformed into standard deviation scores
Pubertal development can be determined by the individual Tanner stage, the role of puberty as an endocrine confounder for reference values remains largely ambiguous
Summary
Relevant reference intervals are a mandatory precondition for the interpretation of endocrine biomarker measurements. The absolute level of the biomarker is determined by the basal stage and functional capacity of the hormone-producing cells. Age and sex are the most important covariates because both determine growth and maturity during childhood. At the onset of adolescence, puberty-induced sex hormones can be observed and may stimulate the hormone levels of the related endocrine axis (e.g., the bone turnover marker). Pubertal development can be determined by the individual Tanner stage, the role of puberty as an endocrine confounder for reference values remains largely ambiguous. This is mainly caused by the issue that patients, physicians or study assistants frequently refuse the examination of pubertal features of adolescents
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