Optic Neuropathy in McCune-Albright Syndrome: Effects of Early Diagnosis and Treatment of Growth Hormone Excess

Context: GH excess is a serious complication of McCune-Albright syndrome (MAS) and has been associated with craniofacial morbidity. Objective: The aim of the study was to determine whether early diagnosis and treatment of MAS-associated GH excess prevents optic neuropathy and hearing impairment, the major morbidities associated with GH excess. Design and Setting: A retrospective cross-sectional analysis was conducted at a clinical research center. Patients: Twenty-two subjects with MAS-associated GH excess and 21 control MAS subjects without GH excess were included in the study. Intervention: Biochemical testing included random GH, nadir GH after glucose load, nadir GH on frequent sampling, and IGF-I Z-score. Subjects underwent imaging, ophthalmological, audiological, and otolaryngological assessment. Treatment included octreotide, pegvisomant, transphenoidal surgery, and/or radiotherapy as indicated. Main Outcome Measure: Association of optic neuropathy and hearing impairment to age at GH excess diagnosis/treatment was measured. Results: Of 129 MAS subjects, 26 (20%) were diagnosed with GH excess based on elevation of two measures of GH function. Of these, 22 subjects were candidates for pharmacological intervention. Optic neuropathy was significantly correlated with intervention status, with no cases in the early intervention group (diagnosed/treated before age 18) or the control group, and four of seven (57%) in the late intervention group (diagnosed/treated after age 18) (Fisher's exact test; odds ratio, 0.027; P = 0.0058). Early diagnosis/intervention was not associated with reduction in hearing deficits (odds ratio, 1.25; P = 1.00). Mean head circumference sd score was significantly higher in the late (6.08; range, 2.70 to 22.56) than the early intervention (2.67; range, −0.65 to 6.72) or control groups (2.13; range, −2.06 to 7.79) (P = 0.003). Conclusions: Early diagnosis/treatment of GH excess in MAS is important to prevent optic neuropathy and craniofacial expansion. The relationship between hearing deficits and GH excess remains less clear and requires further study.