ESPE Abstracts

Objectives: We aim ed to validate first-morning-voided (FMV) total urinary luteinizing hormone immunoreactivity (U-LH-ir) as a marker for the onset of biochemical puberty and as a noninvasive method to predict the imminent onset of clinical puberty.

Methods: We analyzed 651 children (305 boys aged 2.8–17.8 years and 346 girls aged 2.6–18.0 years, both spanning Tanner stages 1-5) across two distinct cohorts. In one cohort, FMV total U-LH-ir levels in 297 children were analyzed using ROC analysis to predict early morning serum LH (S-LH) concentrations at or above 0.3 IU/L, an established criterion for hypothalamic–pituitary–gonadal axis activation. In another cohort of 354 children, we assessed day-to-day variability by calculating the coefficient of variation (CV) in FMV total U-LH-ir over three consecutive days, along with spot S-LH measurements. An immunofluorometric assay (Delfia, PerkinElmer, Finland) was used to determine U-LH-ir from intact LH, the LH beta-subunit, and its core fragment.

Results: ROC analysis revealed that FMV total U-LH levels of 0.60 IU/L in girls and 0.63 IU/L in boys predicted early morning S-LH levels of ≥0.3 IU/L with 97.4% sensitivity and 90.6% specificity. Higher cutoff levels (0.78 IU/L for boys and 0.79 IU/L for girls) increased specificity to 94.7% but reduced sensitivity to 94.1%. The areas under the curve were 0.98 for boys and 0.99 for girls. Despite a 32.7% CV in U-LH-ir levels, only 3.6% of boys and 4.9% of girls had inconsistent test results within the prepubertal (<0.60 IU/L), peripubertal (0.60-0.99 IU/L), and pubertal (≥1.00 IU/L) groups, based on the first cohort's results. U-LH-ir levels confirmed the sex-independent timing of biochemical puberty activation (mean age 10.3 years in boys and 10.5 years in girls). The onset of biochemical puberty in boys was evident even at a testicular volume of 1-2 mL.

Conclusion: An FMV total U-LH-ir cutoff level of 0.6 IU/L has been validated as a novel and reliable marker for detecting the onset of biochemical puberty in both sexes. This noninvasive method is also a clinically useful test for determining biochemical prepuberty (<0.60 IU/L), peripuberty (0.60-0.99 IU/L), and puberty (≥1.00 IU/L), providing guidelines with specific U-LH-ir levels. This innovative approach confirmed our earlier findings, including the sex-independent timing of biochemical puberty occurring long before clinical signs, as well as the longer lag time from biochemical to clinical puberty in boys compared to girls.