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Risk Factors for the Development of Obesity in Children Surviving Brain Tumors

Departments of Endocrinology (R.H.L., K.S., S.R.R., R.K.D., G.A.B.), Biostatistics (X.X., S.W.), and Radiation Oncology (T.E.M.), St. Jude Children’s Research Hospital, Memphis, Tennessee 38105; and Chicago Medical School (S.R.P.), North Chicago, Illinois 60064-3095

Address all correspondence and requests for reprints to: Robert H. Lustig, M.D., Division of Pediatric Endocrinology, Box 0136, University of California San Francisco, 500 Parnassus Avenue, San Francisco, California 94143-0136. E-mail: rlustig{at}peds.ucsf.edu.

Hypothalamic obesity, a syndrome of intractable weight gain due to hypothalamic damage, is an uncommon but devastating complication for children surviving brain tumors. We undertook a retrospective evaluation of the body mass index (BMI) curves for the St. Jude Children’s Research Hospital brain tumor population diagnosed between 1965 and 1995 after completion of therapy to determine risk factors for the development of obesity. Inclusion criteria were: diagnosis less than 14 yr of age, no spinal cord involvement, ambulatory, no supraphysiologic hydrocortisone therapy (>12 mg/m²·d), treatment and follow-up at St. Jude Children’s Research Hospital, and disease-free survival greater than 5 yr (n = 148). Risk factors examined were age at diagnosis, tumor location, histology, extent of surgery, hydrocephalus requiring ventriculoperitoneal shunting, initial high-dose glucocorticoids, cranial radiation therapy, radiation dosimetry to the hypothalamus, intrathecal chemotherapy, and presence of endocrinopathy. Analyses were performed both between groups within a risk factor and against BMI changes for age in normal children older than 5.5 yr (the age of adiposity rebound).

Risk factors were: age at diagnosis (P = 0.04), radiation dosimetry to the hypothalamus (51–72 Gy, P = 0.002 even after hypothalamic and thalamic tumor exclusion), and presence of any endocrinopathy (P = 0.03). In addition, risk factors when compared with BMI slope for the general American pediatric population included: tumor location (hypothalamic, P = 0.001), tumor histology (craniopharyngioma, P = 0.009; pilocytic astrocytoma, P = 0.043; medulloblastoma, P = 0.039); and extent of surgery (biopsy, P = 0.03; subtotal resection, P = 0.018).

These results verify hypothalamic damage, either due to tumor, surgery, or radiation, as the primary cause of obesity in survivors of childhood brain tumors. In particular, hypothalamic radiation doses of more than 51 Gy are permissive. These results reiterate the importance of the hypothalamus in energy balance, provide risk assessment criteria for preventative measures before the development of obesity in at-risk patients, and suggest therapeutic strategies to reduce the future development of obesity.

This work was supported in part by the Cancer Center Support CORE Grant, P30CA12765, and the American Lebanese Syrian Associated Charities.

Present address for R.H.L.: Department of Pediatrics, University of California San Francisco, San Francisco, California 94143-0136.

Present address for K.S.: Division of Pediatric Oncology, Siriraj Hospital, Mahidol University, Bangkok, 10700 Thailand.

Present address for S.R.R.: Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229-3039.

Abbreviations: ALL, Acute lymphoblastic leukemia; BMI, body mass index; CDC, Centers for Disease Control; CrXRT, cranial radiation therapy; Gy, Gray; SJCRH, St. Jude Children’s Research Hospital; VMH, ventromedial hypothalamus; V-P, ventriculoperitoneal.

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