COMPARISON BETWEEN SPONTANEOUS GONADOTROPIN CONCENTRATION PROFILES AND GONADOTROPIN-RESPONSE TO LOW-DOSE GONADOTROPIN-RELEASING-HORMONE IN PREPUBERTAL AND EARLY PUBERTAL BOYS AND PATIENTS WITH HYPOGONADOTROPIC HYPOGONADISM - ASSESSMENT BY USING ULTRASENSITIVE, TIME-RESOLVED IMMUNOFLUOROMETRIC ASSAY

To assess whether nocturnal gonadotropin concentration profiles in children could be predicted by measurement of peak gonadotropin levels after gonadotropin-releasing hormone (GnRH) administration, we measured spontaneous gonadotropin levels every 20 min and the gonadotropin responses to low-dose GnRH using an ultrasensitive, time-resolved immunofluorometric assay in 61 boys with short stature and/or delayed puberty. Spontaneous nocturnal LH pulses were observed in 58 out of 61 patients. After GnRH administration in a dose of 25 ng/kg, all of the 61 patients had significant LH and FSH responses, and GnRH-stimulated peak LH and FSH levels were highly correlated with maximal spontaneous nocturnal LH and FSH levels, respectively (r = 0.83 for LH and r = 0.91 for FSH; p < 0.00001). Analysis of individual subjects revealed that GnRH-stimulated peak LH levels were almost identical to maximal nocturnal LH levels in the subjects whose GnRH-stimulated peak LH levels were between 5 and 10 IU/L, whereas GnRH-stimulated peak LH levels tended to be higher than maximal nocturnal levels in the subjects whose GnRH-stimulated peak LH levels were 5 IU/L or lower. To determine if there were any parameters in the gonadotropin response to GnRH that might be useful in distinguishing early pubertal boys from prepubertal boys, we evaluated the gonadotropin response to GnRH in 44 prepubertal and 10 early pubertal normal short boys. Although maximal nocturnal LH levels did not overlap between prepubertal and pubertal groups, GnRH-stimulated LH peak levels overlapped considerably between the two groups. Even the GnRH-stimulated peak LH to peak FSH ratio overlapped between the two groups. In conclusion, although the use of an ultrasensitive assay enabled us to detect gonadotropin response to GnRH stimulation in a dose of 25 ng/kg in all of the subjects, it was difficult to predict the precise changes in spontaneous circulating gonadotropin concentrations around the onset of puberty simply by measurement of gonadotropin peak levels after GnRH administration.