New reference intervals for endocrinological biomarkers in pediatric patients

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madman

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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 bonemarker 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.
Materials and methods




Laboratory assessment

Venous blood was taken in the morning between 7:30 and 10:00 from 90% of subjects who had fasted overnight, 96% by 11:00, 99% by 12:00 and 100% by 16:00. Samples were processed by trained staff at the LIFE Biobank following standard operating procedures and sent directly to the Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostic at the University Hospital Leipzig.

Steroid hormones in serum were simultaneously quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) after solid phase extraction. Steroids can be analyzed in 4 min after a single manual dilution and protein precipitation step. Method specifications were recently described in detail in refs. [7, 8]. The remaining biomarkers were measured by electrochemiluminescence assays (ECLIA) via Cobas® 601 or 801 (Roche Diagnostics GmbH, Germany).








We conclude that age- and gender-specific referencei ntervals are important for the correct interpretation of hormone measurements in infants, children and adolescents. In addition, confounding factors such as puberty, BMI and the use of contraceptives should be considered when hormones are used for the diagnosis and treatment monitoring of endocrine diseases.
 
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