498 TREATMENT OF TRUE PRECOCIOUS PUBERTY (TPP) WITH AN INTRANASAL (IN) LUTEINIZING HORMONE RELEASING FACTOR (LRF) AGONIST (A)

Abstract

Potent LRF Agonists administered subcutaneously (SC) or IN have proven useful in the treatment of TPP. We studied a new LRF-A, D Nal6 LRF (Nafarelin acetate (NA), Syntex) in 7 girls (age 2–7y) and 2 boys (age 8–9y) with TPP (treatment duration 1.5–6 months (M)). NA 2μg/kg was given SC OD for 2 weeks (W) and 400μg IN OD thereafter. Plasma NA was measured by RIA after the first SC and IN doses. Plasma delta LH (ΔLH) and FSH (ΔFSH) after LRF lOOμg IV, estradiol (E2) and testosterone (T) were measured at baseline, 6W and 3M intervals thereafter. Results are summarized below as mean ± SEM (paired t test): at 6W, ΔLH 2.3±0.6ng/ml (p<0.02), ΔFSH 0.7±0.2ng/ml (p<0.01), E2 23±7pg/ml (p<0.04), T 36ng/dl (n=2); at 3M, ΔLH 1.4±0.2ng/ml (p=0.05), ΔFSH 0.3±0.2 ng/ml (p=0.025), E2 10pg/ml (n=2), T 7ng/dl (n=2) compared to baseline ΔLH 10.2±3.6ng/ml, ΔFSH 3.7±1.1ng/ml, E2 53±12pg/ml and T 373ng/dl (n=2). Plasma NA levels peaked 20 min after SC NA (3.34±0.2ng/ml) and IN NA (1.88±0.7ng/ml) and were measurable (>0.05ng/ml) 8h after SC NA (9/9 patients) and IN NA (7/9). 6/7 girls had menses in the first M on treatment; however, no further vaginal bleeding has occurred. Growth velocity decreased from 11.7cm/y before treatment to 6cm/y after 6M (n=3). Preliminary results suggest IN D Nal6 LRF is an effective treatment for TPP in children.