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Genetic and Rare Diseases Information Center (GARD)

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Other Names for this Disease
  • Familial Testotoxicosis (subtype)
  • Precocious puberty, male limited
  • Pubertas Praecox
  • Sexual precocity, familial, gonadotropin-independent
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Your Question

My uncle, my brother, and one of my brother's sons have testotoxicosis. My son is also affected. I took my son to an endocrinologist and he treated my son with ketoconazole. Treatment was stopped when my son was 11 years old. He continued to grow until the age of 13. Now he is 14 and is 5'7".  We are in the process of going back to the doctor that treated my son to get an x-ray of his hand to see if the growth plates have grown together. Has ketoconazole been proven to work successfully in boys with testotoxicosis?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is 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]
Last updated: 2/29/2012

How might testotoxicosis be treated?

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] 
Last updated: 2/29/2012

Has ketoconazole been proven to work successfully with boys with testotoxicosis? 

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]
Last updated: 2/29/2012

What is the prognosis for boys diagnosed with testotoxicosis?

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]
Last updated: 2/29/2012