Accelerated lower extremity epiphyseal maturation in a prepubertal, growth hormone-deficient girl after treatment for sacral ganglioneuroblastoma

We sought to determine the cause of short stature in a 9-year-old girl who was referred to the University of Texas M.D. Anderson Cancer Center for evaluation of this condition. At 4 years of age she had been found to have a large epidural and presacral ganglioneuroblastoma and had received radiotherapy followed by surgical resection. Systemic chemotherapy (ifosphamide, vincristine, and dacarbazine for 10 courses) was followed by treatment with cis-retinoic acid until the child was 7 years and 4 months old. She has been disease free with no further treatment for an additional 2 years. Decreased growth hormone (GH) secretion was suggested by abnormal clonidine testing (peak GH 0.8 ng/ml), abnormal arginine testing (peak GH 4.3 ng/ml) and delayed wrist bone age. Most abnormal was her skeletal survey; there was almost complete fusion of the epiphyseal growth centers of both femora, proximal tibiae and fibulae. The bones of the upper extremities and spine were normal. Comparison with the first skeletal survey confirmed that these leg bone abnormalities were clearly not present at the time of cancer diagnosis 5 years earlier. Growth failure in this child resulted from accelerated lower extremity epiphyseal maturation. This abnormality followed successful multimodality therapy for cancer, which included prolonged administration of retinoic acid. We suggest that this agent contributed to the patient's skeletal complications.