Gonadal dysfunction after treatment of intracranial tumours.

Abstract

SUMMARY Ninety three children (51 boys, 42 girls) who had been treated for brain tumours not affecting the hypothalamopituitary axis, were studied for evidence of gonadal dysfunction. All had received cranial irradiation, 59 spinal irradiation, and 28 adjuvant chemotherapy. Mean age at treatment was 6-3 years (range 1.5-15). Mean follow up after completion of radiotherapy was 8-5 years (range 1-27). Primary ovarian damage occurred in seven out of 11 (64%) girls treated with craniospinal irradiation alone and in nine out of 14 (64%) of those treated with craniospinal irradiation and chemotherapy. The association with spinal irradiation was significant. Primary gonadal damage also occurred in three out of four children treated with chemotherapy combined with cranial irradiation and in three out of nine boys treated with chemotherapy and craniospinal irradiation but in no boy given craniospinal irradiation alone. The only common chemotherapeutic agent was a nitrosurea. Hypogonadotrophic hypogonadism was found in seven boys, 5-8% of children of pubertal age.Primary gonadal dysfunction is a well known complication of the treatment of some childhood malignancies, particularly leukaemia and lymphoma.'-8The prevalence and aetiology of gonadal dysfunction after treatment of brain tumours in childhood are unclear; this is because reported series are relatively small and because of differences in treatment. Most authors have attributed gonadal damage to scatter from spinal irradiation9 10 but more recently Ahmed et al concluded that adjuvant chemotherapy was responsible.' Brown et al also referred to girls with primary ovarian damage after treatment with lomustine (CCNU) without spinal irradiation.'0) Three affected girls with ovarian damage attributed to spinal irradiation, described by RapVaport et al, had also received chemotherapy.Gonadal dysfunction can also be secondary to gonadotrophin deficiency caused by cranial irradiation 9 12 but there are few data on the incidence after the treatment of childhood brain tumours. Rappaport et al reported that gonadotrophin deficiency may occur infrequently in these patients.9We have studied the aetiology and prevalence of primary and secondary gondal dysfunction in a large cohort of children treated for brain tumours. Patients and methodsAltogether 125 children who were in clinical remission after receiving radiotherapy for brain tumours not affecting the hypothalamopituitary region were studied. Information about gonadal function is reported for 93 of them (51 boys, 42 girls). The remaining 32 children were still prepubertal with serum gonadotrophin concentrations appropriate for age. They were not included in the analysis because hypogonadotrophic gonadal dysfunction cannot be excluded until they reach puberty.' 3 The mean age of the 93 children at treatment was 6-3 years (range 1-5-15) and mean follow up since completion of radiotherapy 8 5 years (range 1-27).Eighty one children were prepubertal when treated, 86 children (48 boys, 38 girls) were of pubertal age when studied. ...

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…The prevalence of POI was reported at 11.8% among female CCS exposed to these highrisk therapies (89). Survivors of CNS tumors may experience POI because of treatment with alkylating agents and ovarian exposure to radiation after craniospinal radiotherapy (119,145). Up to 25.8% of females surviving medulloblastoma experienced POI; this is a likely underestimate given the young age (median age 16.6 years) of this cohort (87, 146).…”

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

“…Even low doses of ionizing radiation to the brain can cause intellectual impairment as well as perturbed growth and puberty. [2][3][4][5][6] RT can cause vascular abnormalities, demyelination and ultimately necrosis. 7 These problems are more pronounced for children who receive RT and the intensity of symptoms seems to be correlated with the age of the child at the time of treatment, such that the younger the child at the time of RT the more severe the symptoms.…”

Endocrine disorders following treatment of childhood brain tumours

“…Cranial irradiation may damage the hypothalamo-pituitary axis leading to growth hormone (GH) deficiency and other endocrine dysfunction. A small number of studies have shown that spinal irradiation has an adverse effect both on spinal growth (Probert et al, 1973;Shalet et al, 1987) and on ovarian and thyroid function (Brown et al, 1983;Shalet et al, 1977a;Oberfield et al, 1986) and that some cytotoxic agents are gonadotoxic (Ahmed et al, 1983;Livesey & Brook, 1988). There has been no large unselected study of the prevalence of these disorders and their implications.…”