Clinical Use of Urinary Gonadotropin Determinations in Children and Adolescents

This study was undertaken to assess the feasibility of non-invasive sampling and assay of urinary gonadotropins for clinical evaluation of pubertal development. In the first study, the concentrations of LH and FSH in concurrent serum and first-morning-voided (FMV) urine samples of 820 children (486 boys and 334 girls, age 0-17 years) were determined with time-resolved immunofluorometric assay (IFMA). The detection limit of IFMA was 0.018 IU/L for FSH, 0.015 IU/L for LH and 0.012 IU/L for LHspec. It was possible to measure the low prepubertal LH and FSH concentrations reliably in these samples due to the high sensitivity and low detection limits of IFMA. The correlation between serum and urinary gonadotropin values was high (r=0.751; p < 0.001 for FSH and r=0.720; p < 0.001 for LH), and the urinary and serum concentrations were close to each other. Correcting urinary gonadotropin concentrations on the basis of urinary density or creatinine did not improve the correlation. Age-related changes in urinary LH and FSH (U-LH and U-FSH) were examined. The concentrations of U-LH and U-FSH decreased from birth until the child was a few months old, after which the upper range of the U-LH levels of girls remained stable at below 0.5 IU/L until age 9 years and of boys below 1.0 IU/L until age 11 years. The upper range of the U-FSH levels of girls remained below 3.0 IU/L until age 10 years and of boys below the same concentration until age 12 years. The median U-LH concentration during the prepubertal period was about 0.06 for girls and 0.07 for boys. For the boys, this figure rose 10-fold by age 11, 40-fold by age 12 and 50-fold by age 13-14. The overall increase in the median U-LH concentrations was 75-fold from 5 to 15 years and 35-fold from Tanner stage G1 to G5. The corresponding figures for girls were 30-fold by age 11, 70-fold by age 12 and 90-fold by age 14; the overall increase in median U-LH concentrations was 90-fold from 5 to 15 years and 40-fold from Tanner stage B1 to B5 times. These finding indicate that the U-LH concentrations of FMV samples obtained from clinically prepubertal children reflect pubertal levels. The age-related changes in U-FSH concentrations were similar for boys and girls; the only difference was that the levels were generally higher for girls, in particular between ages 2 8 years. U-FSH reached a 5-fold level compared to prepubertal levels by the end of the puberty in both sexes. FMV U-LH, U-FSH and their ratios correlated well with the corresponding basal and GnRH-stimulated serum concentrations (P < 0.001). Receiver operating characteristic (ROC) curve analyses of urinary and serum LH and FSH concentrations showed that FMV U-LH and U-LH/U-FSH performed equally well as the GnRH test for differentiating early puberty (Tanner 2) from prepuberty (Tanner 1) [area under the curve (AUC) 0.768-0.890 vs. 0.712-0.858]. FMV U-LH and U-LH/U-FSH performed equally well as basal S-LH for predicting a pubertal GnRH test result (AUCs 0.90 0.93). Among the tests studied, only FMV U-LH differentiated the transitions from Tanner stage 1 to 2 and Tanner stage 2 to 3 (p < 0.001 for boys and p-0.003 for girls). Again, this corroborates that FMV U-LH is the most reliable tool for evaluation of pubertal development. Therefore, FMV urinary LH determinations, which are non-invasive and, at most, minimally stressful for the child patient, can be used for preliminary diagnostic evaluation of pubertal development. It reduces the need for S-LH determinations and the GnRH stimulation tests, both invasive procedures.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2015

Author dc:creator

• Demir, And

• lastentaudit, Lasten endokrinologia

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
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Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/156585

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F156585