This study will examine the effect of pegvisomant on growth hormone excess in patients with
McCune-Albright syndrome (MAS). Patients with this disease have polyostotic fibrous
dysplasia-a condition in which areas of normal bone are replaced with fibrous growth
similar to scar tissue, abnormal skin pigmentation (birth marks) and precocious (early)
puberty. About 10 percent of patients have excess growth hormone (GH). GH stimulates the
production of another hormone called insulin-like growth factor 1 (IGF-1). Together, GH and
IGF-1 affect bone growth. The excess of these hormones in MAS can cause overgrowth of the
bones of the face, hands and feet, excess sweating, or increased height.
Pegvisomant is a synthetic drug that binds to cell receptors where GH would normally bind,
thus preventing the naturally occurring hormone from stimulating IGF-1 and bone growth as it
normally would. This study will see if pegvisomant will reduce blood levels of IGF-1 and
mitigate the effects of growth hormone excess, including bone pain, bone turnover, hand and
foot swelling and sweating, and abnormal levels of related hormones.
Patients who were screened for polyostotic fibrous dysplasia and MAS under NIH protocol
98-D-0145 and were found to have MAS with excess growth hormone are eligible for this
36-week study. The screening protocol includes a history and physical examination, blood
and urine tests, hearing, eye and dental examinations, pain and physical function
evaluations, endocrine and bone screening tests, various bone imaging studies, including
magnetic resonance imaging (MRI) and computed tomography (CT) scans and bone biopsy in
patients over 6 years old.
Participants in the current study will receive daily injections of either pegvisomant or
placebo (an inactive substance) for 12 weeks, followed by a 6-week "washout" period with no
drug. Then, patients who received placebo will be switched, or "crossed over," to receive
pegvisomant for another 12 weeks, and those who received pegvisomant will receive placebo.
This will be followed by another 6-week washout period. The drug and placebo will be
injected under the skin, similar to insulin injections. Blood and urine tests will be done
at the beginning of the study and repeated every 6 weeks until the study ends.
McCune-Albright Syndrome (MAS) was originally described as the triad of polyostotic fibrous
dysplasia of bone, cafe-au-lait skin pigmentation and precocious puberty. Other endocrine
abnormalities have been identified in this disease. Growth hormone (GH) excess is
associated with MAS and occurs in approximately 10% of the patients. Current therapies of
MAS involve separate treatment for the bone and endocrine diseases. We propose to test the
effectiveness of a novel GH receptor antagonist, pegvisomant at reducing the growth hormone
excess in these patients. Secondarily we shall also assess the impact of pegvisomant
therapy on the fibrous dysplastic bone lesions associated with the disease.
The subjects will be patients with MAS and non-suppressible growth hormone as determined by
standard oral glucose tolerant testing (OGTT) and an elevated insulin-like growth factor-1
(IGF-I). It will be a randomized, blinded crossover design. The primary and secondary
measures of efficacy will be: the normalization of serum (IGF-I), a reduction in signs and
symptoms of growth hormone excess, and a net change in Insulin-like Growth Factor Binding
Protein 3 (IGFBP-3). The effect of pegvisomant on the fibrous dysplastic bone activity in
these patients will be determined by a net change in the levels of bone turnover markers.
Diagnosis of PFD/MAS as required in Protocol 98-D-0145
Growth hormone excess will be determined as a non-suppressible serum growth hormone by
oral glucose tolerance test (OGTT). The OGTT parameter will be serum GH greater than 2.0
ng/ml at 60 minutes after an oral load of 75g glucose.
Two consecutive and duplicate measurements of serum IGF-I level should be at least 1.3
times greater than the upper limit of normal (age and sex adjusted according to laboratory