ESPE Abstracts

Introduction: Isotretinoin is used for treatment of dermatological diseases, such as severe acne. It’s also recommended for treatment of high-risk neuroblastoma and pediatric medulloblastoma, but in these cases higher doses are necessary.

Case report: A 12-year-old male patient with poorly differentiated embryonal origin carcinoma in the posterior fossa and implants in the neuroaxis. Next-generation sequencing genetic panel for childhood neoplasms was negative. The oncological treatment was based on the protocol used for high-risk medulloblastoma with ifosfamide, carboplatin, etoposide and vincristine, in addition to central nervous system (CNS) and neuroaxis radiotherapy (36Gy), followed by boost in cervical, thoracic and lumbar spinal implants(45Gy) and in the posterior fossa (54Gy). He received maintenance metronomic chemotherapy for 1 year with oral isotretinoin (100 mg/m²/day; cycles of 21 days). At 14.1 years his height was 147cm(-2,3SD), SH/H 0,53, Tanner pubic hair stage 4, testicular size of 15cm³ and bone age (BA, Greulich-Pyle) of 18 years. Target height 172.3cm(-0.6SD). Before the antineoplastic treatment (11.7 years), he was 142.4cm(-0,7SD) with an average bone age. After 6 months post-treatment: IGF-1 177ng/mL (83-519), LH 3.7mIU/mL, FSH 10mIU/mL and total testosterone 820.3ng/dL.

Discussion: Retinoids regulate cell proliferation, differentiation, morphogenesis and apoptosis, and may be associated with various adverse effects. Studies in animals exposed to retinoids showed disorganization of the growth plate, reduced proliferation and apoptosis of chondrocytes. Asymmetric epiphyseal growth plate arrest, with consequent valgus deformity of the lower limbs, has been previously described in animals and humans exposed to high doses of vitamin A and retinoids. Reduction in GH and IGF-1 levels has been demonstrated in patients treated with isotretinoin for acne, especially in those using higher doses but also in those receiving low continuous doses. Susceptibility to bone effects is related to dose, duration of therapy and age of exposure, which may interfere with growth plate maturation and consequently in the final adult height. The effect of isotretinoin in promoting early growth arrest is evident in the reported patient, with significant advancement of BA. However, there are other growth interferents in adolescents that should be considered such as CNS and neuroaxis radiotherapy and alkylating agent use, despite normal levels of IGF-1, LH, FSH, total testosterone and normal puberty progression.

Conclusion: Isotretinoin can impact in final height by inducing premature fusion of growth plates. It’s suggested that patients undergoing treatment with the drug be carefully monitored, especially if there are any prior concerns about growth.