455 KETOCONAZOLE TREATMENT IN BOYS WITH PRECOCIOUS PUBERTY

Three boys with familial gonadotropin-independent precocious puberty (Rosenthal et al,JCEM 57:571, 1983)were treated with LHRH analog for periods of 1–4 mos, without clinical or biochemical response. The effects of the antifungal drug ketoconazole were studied in these boys prompted by the observation that this agent may interfere with testosterone biosynthesis. With 200mg/12 h P.0. there was an immediate significant fall in serum testosterone(T) from a pre-Rx level of 7.0±1.6 nM/L (mean±SEM)to 1.3±1.1 (N<1.5), with a reciprocal rise in 17-OHP from 2.3±1.5 to 7.2±1.1 nM/L. DHAS and androstenedione levels were unchanged. The T response to hCG remained intact. Major improvement in behavior, linear growth & skeletal maturation were sustained for the duration of treatment.The cortisol response to ACTH1-24 was significantly blunted after 5 days of Rx, but returned to normal after 1 mo with normal diurnal rhythm. Hepatic abnormalities were not observed in up to 9 mos of treatment. We conclude that ketoconazole may provide effective long-term control of precocious puberty in males through C 17–20 lyase inhibition, and speculate that this drug may play an important therapeutic role in other conditions of androgen excess. *cm/yr