Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma

Aims: Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. Methods and results: Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate-shaped S100 protein-positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese-superoxide dismutase. In addition to faint reactivity with anti-cytokeratin 8, 18 antibody, many cells were densely positive with anti-cytokeratin 1, 5, 10, 14 antibody. Conclusions: These results indicate that radiation-induced fibrosis is associated with an increased number of folliculo-stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.