Headliners: Neurodevelopment: Genomewide Screen Reveals Candidate Genes for Neural Tube Defects

We have studied the long-term endocrine effects of treatment on 144 children treated for brain tumours. All received cranial irradiation, 86 also received spinal irradiation and 34 chemotherapy. Almost all patients (140 of 144) had evidence of growth hormone insufficiency. Treatment with growth hormone was effective in maintaining normal growth but could not restore a deficit incurred by delay in instituting treatment. The effect of spinal irradiation on spinal growth was not corrected by growth hormone. As spinal growth makes the major contribution to the pubertal growth spurt and limb length the major contribution to childhood growth, treatment with GH will have maximal effect on leg length if instituted before the onset of puberty. Primary thyroid dysfunction was found in 11 of 47 children (23%) treated with craniospinal irradiation but in none treated with cranial irradiation alone. The incidence rose to 69% of 29 children treated with spinal irradiation and chemotherapy and to 50% of four children treated with cranial irradiation and chemotherapy. This effect of chemotherapy has not previously been reported and was detected by us through measurement of serum TSH concentration. Primary thyroid dysfunction requires treatment with thyroxine to prevent increasing the risk of secondary thyroid tumours. Seven of 20 girls (35%) treated with spinal irradiation had primary ovarian dysfunction as determined by raised gonadotrophin levels. Chemotherapy increased this, but not significantly. Three of 15 boys (20%) treated with chemotherapy had primary testicular dysfunction. Gonadotrophin deficiency occurred in seven boys. Four of 90 children had deficiency of cortisol secretion in response to hypoglycaemia. These results confirm the requirement for long-term follow-up of children treated for brain tumours from the endocrine point of view. Anticipation of hormone deficiencies and replacement treatment can improve the quality of life of survivors. Long-term survival following the treatment of brain tumours in childhood has improved considerably over the past 30 years (Birch et al., 1988). For example, 50% 5-year survival is reported in children with medulloblastoma treated by surgery and post-operative craniospinal irradiation (Al Mefty et al., 1985). A large, prospectively randomised study suggested a role for chemotherapy, particularly in children with adverse prognostic factors (Bloom & Thornton Jones, 1983). It has become clear, however, that the large numbers of children cured of their original tumour are at risk for long-term sequelae, mainly from the radiotherapy (Shalet et al., 1975; Harrop et al., 1976). Cranial irradiation may damage the hypothalamo-pituitary axis leading to …