title: Pediatric brain natriuretic peptide concentrations vary with age and sex and appear to be modulated by testosterone.
abstract: BACKGROUND
  Natriuretic peptide concentrations in adults require age- and sex-specific reference intervals for optimal interpretation. Females have higher natriuretic peptide concentrations, and hypotheses suggest that estrogen may be responsible. This study sought to determine the influence of hormone modulation on N-terminal probrain natriuretic peptide (NT-proBNP) by using a pediatric cohort. Children/adolescents typically have rapid hormone changes during puberty, making them an ideal group to study.
  
  
  METHODS
  We selected 759 specimens (303 male, 456 female; ages 2 months to 18 years, mean 13 years) obtained from the Mayo Clinic Pediatric Residual Specimen Bank. We measured NT-proBNP, sex hormone-binding globulin (SHBG), estradiol, and testosterone by immunoassays or LC-MS/MS and calculated free testosterone. We performed univariate and multivariate analyses to investigate the significance of NT-proBNP with each hormone.
  
  
  RESULTS
  Reference values demonstrated a sex difference and sequential age differences in females. Univariate modeling of the hormones with NT-proBNP revealed an independent inverse association of NT-proBNP with testosterone, a direct association with SHBG, and no significant association with estradiol. Multivariate modeling confirmed a strong association of testosterone and SHBG with NT-proBNP. Correlation of hormones with NT-proBNP retained greater significance than either age or sex.
  
  
  CONCLUSIONS
  In pediatric patients, NT-proBNP is independently associated with both testosterone and SHBG hormone concentrations. Measurements of testosterone are inversely associated with NT-proBNP, and estrogens are marginally associated with NT-proBNP in males but not females, suggesting that androgens and not estrogens modulate sex differences notable in natriuretic peptides. Children and adolescents may require an objective assessment of hormones if optimal interpretation of natriuretic peptide concentrations is desired or the concentrations are confounded. .
authors.affiliation: Department of Laboratory Medicine and Pathology/Division of Clinical Core Laboratory Services, Mayo Clinic, Rochester, MN 55905, USA. saenger.amy@mayo.edu
authors.forename: Amy K
authors.initials: AK
authors.lastname: Saenger
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dalenberg
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Bryant
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Grebe
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D012016:Reference Values; D012737:Sex Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*
chemical_list: D010446:Peptide Fragments; D012738:Sex Hormone-Binding Globulin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013739:Testosterone; D004958:Estradiol