ESPE Yearbook of Paediatric Endocrinology

Brief summary: this early experimental study analyzed the effects of radiation on growth hormone secretion and short-term cell survival in a cell culture model of dispersed rat anterior pituitary cells.

At the time of this study, growth retardation had already been recognized as a significant adverse effect of brain irradiation in humans and experimental animals. Such growth retardation had been associated with impaired secretion of growth hormone in children, but a comparable correlation had not been confirmed in rats.

After a single dose of radiation, survival curves of different rat anterior pituitary cells (classified according to hematoxylin-eosin immunostaining into acidophil, basophil, and chromophobe pituitary cells) were analyzed and compared with control cell cultures unexposed to radiation.

Acidophilic pituicytes were the cells most damaged by irradiation and were sensitive to a single radiation dose higher than 300 rad. On the contrary, basophilic pituicytes showed remarkable resistance to doses as high as 1000 rad. Acidophil cells are characterized by the biosynthesis and secretion of growth hormone and prolactin. Basophil cells synthetize and secrete TSH, ACTH, FSH and LH. Chromophobe cells are resting cells without any hormonal immunoreactivity.

This seminal study showed for the first time that irradiation can selectively damage different pituitary cells depending on the dose used, and that growth hormone-secreting cells show the greatest sensitivity to irradiation-induced damage. The results are consistent with current clinical evidence that lower doses of radiation therapy (18–50 Gy, mainly used in cranial and total body irradiation for leukaemias) produce selective hypothalamic–pituitary dysfunction, which usually manifests as isolated growth hormone deficiency. In contrast, higher doses, such as those used in the treatment of brain tumors, can produce direct damage to the anterior pituitary gland leading to multiple pituitary hormone deficiencies. Growth hormone deficiency represents the earliest and most common endocrine defect induced by brain irradiation, even after relatively low doses. In contrast, central adrenal insufficiency (ACTH deficiency), central hypothyroidism (TSH deficiency), and hypogonadotropic hypogonadism (LH/FSH deficiency) are less common, appear later, and are usually observed only after high doses of cranial irradiation.