Luteinizing Hormone-Releasing Hormone Analog Treatment of Boys with Hypothalamic Hamartoma and True Precocious Puberty

Abstract

A long-acting analog of LRH (LRHa) has been shown to suppress pituitary gonadotropin and estradiol secretion to prepubertal levels in girls with idiopathic true precocious puberty. We treated six boys, aged 1-6 yr, with true precocious puberty due to hypothalamic hamartoma for 6-24 months with daily sc injections of LRHa. The patients had enlarged testes (6-25 ml), Tanner stage II-IV pubic hair, facial and axillary hair, increased growth rate, and an advanced bone age. Frequent erections occurred in all patients. Computed tomography of the head showed abnormalities characteristic of hypothalamic hamartoma (0.5-3 cm in diameter) in each boy. Each patient had measurable LH and FSH levels, with pulsed nocturnal secretion, and pubertal LH and FSH responses to LRH. Serum testosterone was in the range for normal adult men (200-600 ng/dl). LRHa significantly decreased basal LH (P less than 0.005) and FSH levels (P less than 0.01), LRH-stimulated gonadotropin levels (P less than 0.005), and serum testosterone levels (P less than 0.005). Testis size decreased significantly (P less than 0.005). Annualized growth velocity (centimeters per yr) decreased significantly compared to the pretreatment growth rate (P less than 0.01). Bone age advancement per yr slowed significantly during the course of LRHa treatment (P less than 0.01). Pubic hair, facial hair, and erections decreased in all patients. LRHa is an effective treatment for boys with precocious puberty associated with hypothalamic hamartoma. Chronic therapy will be required, however, to assess the ultimate effect of LRHa.