The effect of total body irradiation and bone marrow transplantation during childhood and adolescence on growth and endocrine function

Abstract

Seventeen children (11 M, 6 F) with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophosphamide and single fraction total body irradiation (900-1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority of children exhibited growth failure, which was of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on the reduced growth hormone response to insulin induced hypoglycaemia. Three patients had evidence of hypothalamic damage as shown by their growth hormone response to 200 micrograms GHRH (1-29) NH2 intravenously. Gonadal failure was common, assessed clinically, and biochemically by basal gonadotrophin and sex steroid concentrations. All four girls of adolescent age (10.6-14.1 years) had ovarian failure requiring sex steroid replacement. Of the eight boys of adolescent age (12.3-18.3 years), two had testicular failure requiring sex steroid supplements. Both of these had had previous testicular irradiation. Five others had compensated gonadal failure, and one had normal Leydig cell function. Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy.