Premature Epiphyseal Closure of the Lower Extremities Contributing to Short Stature after cis-Retinoic Acid Therapy in Medulloblastoma: A Case Report.

TitlePremature Epiphyseal Closure of the Lower Extremities Contributing to Short Stature after cis-Retinoic Acid Therapy in Medulloblastoma: A Case Report.
Publication TypeJournal Article
Year of Publication2016
AuthorsNoyes JJ, Levine MA, Belasco JB, Mostoufi-Moab S
JournalHorm Res Paediatr
Volume85
Issue1
Pagination69-73
Date Published2016
ISSN1663-2826
KeywordsAdult, Bone Diseases, Child, Female, Growth Disorders, Growth Plate, Human Growth Hormone, Humans, Lower Extremity, Medulloblastoma, Tretinoin
Abstract

BACKGROUND: Prolonged cis-retinoic acid (RA) exposure contributes to premature epiphyseal closure. cis-RA is administered in various treatment regimens for pediatric cancers, thus increasing the risk for bone deformities and compromised growth.

RESULTS: We present a case of premature epiphyseal closure in a 9-year-old female with a history of medulloblastoma and treatment with a multimodal regimen including cis-RA. She was subsequently diagnosed with radiation-induced endocrine late effects including hypothyroidism and growth hormone deficiency (GHD). Seven months after initiation of GH therapy, an increased prominence of the wrists and knees combined with a deceleration in growth velocity prompted further evaluation; radiographs revealed bilateral premature closure of the distal femur and proximal tibia growth plates despite normal left wrist bone age.

CONCLUSION: High doses of vitamin A and its analogs are linked to premature closure of the lower-extremity growth plates in animals and children. Pediatric brain tumor patients are at increased risk of growth failure due to concurrent radiation-induced GHD, damage to the spinal bones, and cis-RA-associated premature closure of the lower-extremity growth plates, with significant reduction in adult stature. A better appreciation of the detrimental effect of cis-RA on the growing skeleton is needed to monitor at-risk patients and to provide timely interventions.

DOI10.1159/000441140
Alternate JournalHorm Res Paediatr
PubMed ID26457578
PubMed Central IDPMC4743750
Grant ListK07 CA166177 / CA / NCI NIH HHS / United States