USE OF LEUPROLIDE ACETATE RESPONSE PATTERNS IN THE EARLY DIAGNOSIS OF PUBERTAL DISORDERS - COMPARISON WITH THE GONADOTROPIN-RELEASING-HORMONE TEST

The effects of a single injection (500 mu g sc) of the GnRH agonist leuprolide acetate on gonadotropin secretion and those induced by a GnRH test were analyzed in 32 children (11 males and 21 females) referred for possible pubertal developmental disorders and in 9 prepubertal controls [group C; 4 males and 5 females; chronological age (CA), 7.4 +/- 1.2 yr]. The pituitary-gonadal secretory responses to the GnRH agonist were characterized in all subjects and in a control group in early puberty [10 females (Tanner breast stage II; CA, 11.3 +/- 1.1 yr) and 6 males (Tanner pubertal stage II; CA, 13.5 +/- 0.4 yr); group D]. Twelve girls (CA, 7.1 +/- 0.7 yr) presented with precocious breast development, 11 patients [6 boys (CA, 10.9 +/- 0.4 yr) and 5 girls (CA, 9.3 +/- 0.5 yr)] had advanced puberty and predicted adult heights below -2.0 SD score, and 9 patients [5 boys (CA, 14.6 +/- 0.3 yr) and 4 girls (CA, 14.4 +/- 1.1 yr)] had delayed puberty. Less than 6 months had elapsed since the appearance of pubertal signs in all patients with pubertal development. After a follow-up period of 12.9 +/- 2.0 months, 20 patients showed progression of pubertal signs (group A, progressive puberty), and in 12, puberty regressed or did not progress (group B, nonprogressive puberty). The results of hormonal tests in all patients were analyzed retrospectively according to their clinical outcome. Patients in group A had a mean plasma peak LH response significantly higher after leuprolide acetate stimulation than after GnRH challenge (13.1 +/- 0.2 vs. 7.3 +/- 0.9 IU/L; P < 0.003). Those in groups B and C had similar peak LH responses after both tests (3.3 +/- 0.2 vs. 3.1 +/- 0.4, and 1.5 +/- 0.1 vs. 1.8 + 0.4 IU/L, respectively). No differences in basal and poststimulated LH levels were found between boys and girls in the same group. In patients in groups A and D, LH consistently peaked 3 h postleuprolide acetate challenge; in those,in groups B and C, the LH peak occurred 3-6 h postinjection. Maximal gonadal responses were elicited 24 h poststimulation. No overlap in poststimulated estradiol or testosterone values occurred between patients in groups A and D and those in groups B and C. A peak LH response above 8 IU/L after leuprolide acetate challenge was consistently seen in all patients in groups A and D, and was invariably accompanied by a distinct gonadal steroid response (estradiol, greater than or equal to 150 pmol/L; testosterone, greater than or equal to 3.15 nmol/L). Only 40% of patients with progressive puberty had similar LH responses after GnRH testing. Our results suggest that leuprolide acetate stimulation may be useful for the early diagnosis of pubertal disorders. The ability of leuprolide acetate to assess both gonadal and pituitary function would make testing with this agent more widely applicable than GnRH stimulation.