Testotoxicosis

Testotoxicosis is a form of gonadotropin-independent precocious puberty in which boys experience early onset and progression of puberty. The disease generally presents between 2 and 4 years of age. Patients have accelerated growth, early development of secondary sexual characteristics and reduced adult height. Testotoxicosis is caused by an activating mutation of the luteinizing hormone receptor (LHCGR) gene, which leads to increased levels of sex steroids in the context of low luteinizing hormone. The condition may be sporadic or transmitted as a dominant trait. It is only expressed in males.^[1][2][3][4] Treatment consists of reducing hyperandrogenism in children (sexual maturation, stature), with ketoconazole or a combination of antiandrogens and aromatase inhibitors.^[4]

Decisions regarding treatment for patients with testotoxicosis are complex.^[3] Treatment typically consists of reducing hyperandrogenism in children (sexual maturation, stature) with ketoconazole or a combination of antiandrogens and aromatase inhibitors.^[3][4] Recently, the use of combination therapy with bicalutamide (a potent antiandrogen agent) and anastrozole or letrozole (third-generation aromatase inhibitors) was reported to yield encouraging short-term results, including slower growth rate.^[5][6] 

Ketoconazole blocks enzymes in the steroid biosynthetic pathway. It primarily inhibits C-17,29-desmolase, the enzyme responsible for androstenedione biosynthesis. This medication, which is more commonly used for treating fungal infections, may be used in treating precocious pseudopuberty. It inhibits steroid synthesis at the level of 17 á -hydroxylase/17,20-lyase, a key enzyme in sex steroid production. It also inhibits testosterone binding to its binding globulin.^[3] Long-term treatment with ketoconazole appears to significantly decreased the bone age/chronological age ratio without significant side-effects in boys with testotoxicosis. However, this therapy shows limited efficacy in attaining normal adult height.^[7]

The complications associated with testotoxicosis are related to early sexual and physical maturation. Other complications are psychological and related to the early sexual and physical maturation. In general, prognosis is excellent with proper treatment.^[3]