A severe case of testotoxicosis in an infant due to a c.1732G>C (p.ASP578His) LHCGR gene mutation associated with nodular Leydig cell hyperplasia

Introduction: Testotoxicosis is a rare gonadotropin-independent form of precocious puberty. Herein we discuss a uniquely severe case of severe testotoxicosis in infant male with a c.1732G>C (p.ASP578His) LHCGR gene mutation requiring surgical intervention. Case Description: This 9-month-old male initially presented with extremely elevated levels of testosterone (1383 ng/dl) and undetectable ultrasensitive LH and FSH titers. On physical exam he was Tanner stage 3. Scrotal ultrasound showed multiple bilateral nodular hypoechoic lesions. A genomic DNA 1732G->C mutation within the LHCGR gene leading to a p.Asp578His amino acid change was confirmed on genetic testing. Combination medical therapy with an androgen receptor blocker and aromatase inhibitor was initiated for testotoxicosis; however, his condition worsened on medical therapy with a further rise in testosterone levels (2177 ng/dl). He subsequently underwent 2 sequential orchiectomies for his condition with both pathologies demonstrating diffuse nodular Leydig cell hyperplasia. Conclusions Herein we report the youngest case of medically refractory testotoxicosis associated with progressive bilateral diffuse nodular Leydig cell hyperplasia requiring aggressive surgical intervention. The germline c.1732G>C (p.ASP578His) mutation found in this case was previously described as somatic mutations in 3 boys with benign nodular adenoma of the testes.