The precocious puberty of McCune-Albright Syndrome (MAS) in girls is characterized by sporadic development of functional ovarian cysts leading to transient elevations in serum estradiol. Although significant clinical heterogeneity exists, a subset of patients develop relentlessly progressive precocious puberty resulting in premature epiphyseal closure and compromised adult stature. The most recent therapeutic approach has been the use of aromatase inhibitors such as testolactone. Unfortunately the use of these agents has been characterized by problems with both efficacy and compliance. We report a case of MAS in which tamoxifen was used to treat progressive precocious puberty with dramatic results.

The patient is a 7 9/12 year old African-American female who presented with precocious puberty at 2 5/12 years. Clinical, biochemical and radiographic findings led to a diagnosis of MAS. Initial bone age x-ray was 3 5/12 yrs(>+2SD). Because of frequent menses (monthly) and growth acceleration (16.8 cm/yr), the patient was started on testolactone (22 mg/kg/d). Over the next 13 months, precocious puberty advanced unchecked, despite an increase in the testolactone to 35 mg/kg/d. At age 4 years, medication was discontinued due to treatment failure. At 4 6/12 years, bone age had advanced to 10 years, and predicted adult height was 54 inches. At 4 9/12 years, breasts were Tanner IV, growth velocity was 14 cm/yr and monthly bleeding continued. IRB approval was then obtained for the experimental use of tamoxifen in this patient. In response, she experienced immediate cessation of menses and had a precipitous drop in growth velocity, rate of skeletal maturation and pubertal progression.

Puberty has now been successfully arrested in this patient for almost three years while on tamoxifen (10 mg TID) with no apparent adverse effects. GnRH analog therapy was added when onset of central precocious puberty was noted. Growth velocity is now normal, bone age is 11 6/12 years, and height prediction has improved to 60 inches. These results suggest that tamoxifen may have a valuable role in the supression of estrogen action and precocious puberty in MAS, and may lead to superior results than those achieved with aromatase inhibitors. A prospective and controlled clinical trial is needed to further investigate the safety and efficacy of tamoxifen for the treatment of progressive precocious puberty in patients with MAS.