SUN-187 Gonadotropin-Releasing Hormone Agonist Resistant Central Precocious Puberty in Males with Hypothalamic Hamartoma: A Two-Center Case Series

Abstract Disclosure: Z.A. Erbowor-Becksen: None. D. Mak: None. V.C. Benavides: None. Background: Central precocious puberty (CPP) is a common clinical scenario treated amongst pediatric endocrinologists. CPP typically responds well to gonadotropin-releasing hormone agonists (GnRHa), with resistance rarely reported. The paucity of GnRHa-resistant cases presents a therapeutic challenge, as alternative treatment protocols remain poorly defined.Clinical Cases: We conducted a two-center case series following male patients with GnRHa-resistant CPP associated with hypothalamic hamartoma. Patient follow-up ranged from 2 to 10 years. Treatment efficacy was evaluated through serial bone age/chronological age (BA/CA) ratios, anthropometric measurements, and hormonal parameters. The initial presentation occurred at ages 1 and 3 years. Both children had evidence of bilateral testicular enlargement, with baseline testosterone levels averaging 501 ng/dL (<7-20 ng/dL) and markedly advanced BA/CA ratios (2.25 and 2.0). Work-up for other causes of pubertal onset was unremarkable. In both cases, therapy included one GnRHa and an aromatase inhibitor; one case included an antiandrogen agent (bicalutamide) as a third agent. Overall, treatments were well tolerated, with no reports of hepatotoxicity. Testosterone was not entirely suppressed, with a mean post-treatment testosterone level of 61 ng/dL at the last follow-up. The patient receiving triple therapy demonstrated progressive improvement in BA/CA ratio (2.25 to 1.07), height velocity (12.7 to 4.8 cm/year), and height SDS (2.05 to 0.94) over 10 years. The patient receiving dual therapy showed testosterone suppression (457 to 85.6 ng/dL) but maintained accelerated growth (height velocity 16.9 cm/year) and advancing BA/CA ratio, suggesting incomplete pubertal suppression.Conclusion: In males with hypothalamic hamartoma-associated GnRHa-resistant CPP, triple therapy combining GnRHa, aromatase inhibitors, and antiandrogens demonstrated superior efficacy over dual treatment. It achieved near-normalization of growth parameters, bone maturation, and endocrine profiles without compromising safety. Treatment was well-tolerated during long-term follow-up. These findings suggest a potential therapeutic strategy for GnRHa-resistant CPP, though more extensive studies are needed to confirm optimal treatment protocols. Presentation: Sunday, July 13, 2025