The diagnostic value of first-voided urinary LH compared with GNRH-stimulated gonadotropins in differentiating slowly progressive from rapidly progressive precocious puberty in girls

Abstract

Objective: Characterization of pubertal progression is required to prevent unnecessary intervention in unsustained or slowly progressive (SP) precocious puberty (PP), while delivering hormonal suppression in rapidly progressive (RP) PP. We aimed to assess the diagnostic value of first-voided urinary LH (ULH) compared with GNRH-stimulated gonadotropins in differentiating these forms of PP. Methods: A total of 62 girls with PP underwent both GNRH stimulation and ULH assay. Fifteen girls with peak LH R10 IU/l started treatment immediately, whereas the other 47 girls were evaluated after 6 months for pubertal advancement, height acceleration, and bone-age maturation. Based on these criteria, the participants were assigned to five subgroups: pubertal regression, no progression or progression by one, two or three criteria. The first three subgroups were defined as SP-PP (nZ29), while the other two subgroups were defined as RP-PP (nZ18). An additional 23 prepubertal girls were evaluated for ULH. Results: ULH but not serum gonadotropins could distinguish girls with two and three criteria from less progressive subgroups. By comparison with SP-PP (i.e. regression group and groups 0 and 1), those with RP-PP (group 2C3) had lower peak FSH (9.28G2.51 vs 12.57G4.30; PZ0.007) and higher peak LH:FSH ratio (0.42G0.30 vs 0.22G0.12; PZ0.022) and ULH (1.63G0.65 vs 1.05G0.26 IU/l; P!0.001). Based on receiver operating characteristics analysis, a ULH cutoff of 1.16 IU/l had a better sensitivity (83%) and positive and negative predictive values (65 and 88% respectively) than the other two parameters, with a specificity of 72%. Conclusions: ULH assay is a noninvasive, reliable method that can assist in the distinction between SP-and RP-PP.

First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test

“…FMV U-LH also correlated very well with S-LH max and so did the FMV U-LH/U-FSH ratio with the S-LH max /S-FSH max ratio. This is in line with previous studies on girls with precocious puberty: Witchel et al [25] found a good correlation between 24-h U-LH and S-LH max in 18 girls on GnRH analog treatment, and Zung et al [26] between FMV U-LH and S-LH max and the S-LH max /S-FSH max ratio in 47 girls with signs of precocious puberty. On the basis of the excellent correlations between the FMV U-LH and S-LH max concentrations in this study, it is not surprising that the FMV U-LH concentrations and U-LH/U-FSH ratios correlated at least equally well as S-LH max and the S-LH max /S-FSH max ratios with the pubertal developmental stage (slightly higher r values for the urine tests).…”

“…interpretation of thelarche as a definite sign of puberty. It is also of note that the cut-off values of the GnRH test used here for a pubertal response were quite demanding (see discussion in [26]). Girls may need a slightly lower S-LH max cut-off value than boys in the GnRH test.…”

“…Determination of FMV U-LH may also be valuable for monitoring the progression and treatment of precocious puberty as recently suggested by Zung et al [26]. …”

The measurement of urinary gonadotropins for assessment and management of pubertal disorder

“…Recent reports in children with early puberty have suggested that uGn excretion can differentiate between those with slowly-progressive and rapidly-progressive precocious puberty. 21 The value of performing LHRH stimulation in all suspected cases of early puberty has been questioned recently 21 and it would indeed be beneficial to consider a more convenient alternative or screening test. In the current study, there was the impression that uGn excretion was higher in those with true puberty, characterised by a peak LH of >5U/L on LHRH stimulation, compared to other cases with early puberty with a peak LH of <5U/L; however, the number of cases in the latter group were not high enough to statistically confirm this difference.…”

Random urinary gonadotropins as a useful initial test for girls with central precocious puberty

“…In that study, the FMV urinary LH level and LH:FSH ratio exhibited good and excellent diagnostic performance, respectively, for distinguishing early puberty from prepuberty compared with the GnRH stimulation test (an AUC of 0.880 for urinary LH and an AUC of 0.925 for the urinary LH:FSH ratio) [11]. A Jewish study showed increased mean levels of LH in FMV urine samples from girls with rapidly progressive CPP vs. slowly progressive precocious puberty and prepuberty [18]. Zung et al [18] suggested that urinary LH in FMV urine samples can be used to identify rapidly progressive precocious puberty in girls with CPP and/or prepuberty.…”