Familial male - limited precocious puberty

Familial male-limited precocious puberty

Testotoxicosis is a form of gonadotropin-independent (peripheral) 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 usually reduced adult height.

Testotoxicosis is caused by an activating mutation of the luteinizing hormone (LH) receptor, leading to increased levels of sex steroids in the context of low LH

The condition may be sporadic or transmitted as a dominant trait.

Treatment consists of reducing hyperandrogenism in children (sexual maturation, stature), with ketoconazole or a combination of antiandrogens and aromatase inhibitors (2)

• treatment consists in reducing hyperandrogenism in children (sexual maturation, stature)
  • two options have been proposed
    • 1) consists of administrating the androgen antagonist bicalutamide together with aromatase inhibitors such as anastrozole or letrozole to normalize the growth rates until adult height has been reached
    • 2) option consists of administrating androgen biosynthesis inhibitors such as ketoconazole that result in a decrease in testosterone levels
  • in both cases, the treatments may be supplemented by GnRH therapy if central (gonadotropin-dependent) precocious puberty develops
  • psychological counseling is needed to help the patient and family adjust to the stimulative effects of high androgen levels

Prognosis

• prognosis is good
  • with treatment most patients reach an appropriate adult height
  • the disease does not seem to have any consequence during adulthood but this is based on limited clinical reports (2)

Reference:

• Reiter EO, Norjavaara E. Testotoxicosis: current viewpoint.Pediatr Endocrinol Rev 2005 Dec;3(2):77-86
• Carel JC. Testotoxicosis. Orphanet. 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3000. Accessed 17/1/2020