Testotoxicosis is a rare form of precocious puberty caused by a constitutively activating mutation in the luteinizing hormone receptor (LHR) gene. Symptoms include rapid virilization, accelerated growth and reduced adult height. We describe a rare association of testotoxicosis with a metaphyseal chondrodysplasia called cartilage-hair hypoplasia (CHH) and report two brothers with testotoxicosis after 4 years of treatment. The brothers had a T577I mutation in the LHR gene. One brother also presented CHH. The older brother was treated with ketoconazole, then with the aromatase inhibitor anastrozole and the anti-androgen cyproterone acetate. The younger brother received this combination as first-line therapy. Clinical improvements included reductions in growth velocity and bone maturation rate, which should result in taller adult stature. Tolerance was good. CONCLUSION: Combined treatment with anastrozole and cyproterone acetate is effective in improving the prognosis of adult height in testotoxicosis.
[Show abstract][Hide abstract] ABSTRACT: Aromatase inhibitors have been reported to increase height prediction in boys with short stature, and in boys and girls with gonadotropin-independent precocious puberty. The following review discusses data published since 2008 regarding the safety and efficacy of aromatase inhibitors in pediatric patients.
Third-generation aromatase inhibitors in combination with antiandrogens appear effective in preventing bone age advancement and virilization in boys with familial male-limited precocious puberty (FMPP). Letrozole, but not anastrozole, decreased bleeding episodes and bone age advancement in girls with McCune-Albright syndrome (MAS), despite ovarian enlargement. Letrozole-treated boys with idiopathic short stature (ISS) had no loss of bone density but were noted to have more vertebral abnormalities than a placebo group. Two years of letrozole therapy did not increase predicted adult height in pre and peripubertal boys with ISS when re-assessed 4 years after the treatment period.
Aromatase inhibitors together with an antiandrogen appear to be a very promising treatment for FMPP. Further longer-term studies with letrozole are needed in MAS. The prevalence of vertebral deformities should be evaluated prospectively in patients treated with aromatase inhibitors. Adult height data are still lacking in pediatric patients treated with aromatase inhibitors. Two years of therapy in pre and peripubertal short boys does not appear to increase adult height. Hemogram, lipids, and bone density should be periodically assessed in treated patients. Further controlled studies are needed to demonstrate safety and efficacy of aromatase inhibitors in pediatric patients.
Current opinion in pediatrics 05/2010; 22(4):501-7. DOI:10.1097/MOP.0b013e32833ab888 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Testotoxicosis, a form of gonadotropin-independent precocious puberty, results from an activating mutation of the luteinizing hormone receptor expressed in testicular Leydig cells. Affected males experience early testosterone secretion, virilization, advancing bone age, and resultant short stature. Recently, the use of combination therapy with a potent antiandrogen agent (bicalutamide) and a third-generation aromatase inhibitor (anastrozole or letrozole) was reported to yield encouraging short-term results. We present here the results of longer-term treatment (4.5 and 5 years) with this combination therapy in 2 boys who demonstrated that it is well tolerated, slows bone-age advancement in the face of continued linear growth, and prevents progression of virilization.
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