A Rare Cause of Precocious Puberty - Testotoxicosis

Background: Testotoxicosis, also known as familial male-limited precocious puberty (FMPP), is a rare cause of gonadotropin-independent precocious puberty in boys due to an activating mutation in the luteinizing hormone (LH))/choriogonadotropin receptor (LHCGR) gene. Case report: A 3-year 2-month-old boy presented with acne, pubic hair, phallic growth, height accelerations, and aggressiveness. At physical examination, his height was 106cm (+2.36 SDS) and weight was 16kg (+0.77 SDS). He had Tanner stage 2 pubic hair, stretched penile length was 6 cm (>2 SDS), and both testicular volumes were 5mls. Bone age was advanced at 7 years old. Testosterone level was high at 17nmol/L and the gonadotropin-releasing hormone (GnRH) stimulation test was suggestive of peripheral precocious puberty. Whole exome sequencing identified a heterozygous pathogenic variant c.1691A>G (p.Asp564Gly) in the LHCGR gene which supports the diagnosis of testotoxicosis. The child was started on both aromatase inhibitor, anastrozole, and anti-androgen, spironolactone. At 6 months of treatment, there was a halt in pubertal progression with reduced height velocity from 9cm/year to 6cm/year. Conclusion: Without intervention, the patient will have rapid progressive skeletal maturation and virilization which will result in compromised final adult height and psychosocial distress.