In the past, the normal pituitary gland has been thought to be relatively radioresistant, tolerating doses up to 190 Gray without showing pathological damage. In time it became clear that radiation therapy can induce hypopituitarism54. It is the most prevalent late side effect as a result of direct damage to the pituitary and also secondary to hypothalamic damage55, as is evidenced by appropriate pituitary responses to administration of exogenous hypothalamic releasing hormones56-58. There is some evidence to suggest that direct injury to hypothalamic neurones, rather than reduced cerebral blood flow, is the major cause of progressive hypothalamic-pituitary dysfunction after fractionated cranial irradiation. Direct damage to the cell nuclei in the hypothalamus may explain the delayed onset of hormone deficiency, because these cells are dividing slowly and die during mitosis years later before losing their function59. Radiation doses in excess of 50 Gray can have a direct effect upon pituitary function. However, at doses below 50 Gray, hypopituitarism may initially be caused by hypothalamic dysfunction60.
Radiation-induced hypopituitarism depends, besides on the total dose, on fraction size61. It increases in time for at least 10 years62. The severity, as measured by the number of anterior pituitary hormone deficiencies, depends on the total dose. Higher radiation dose given to the pituitary gland will result in a more rapid onset of hypopituitarism60. Among patients who developed multiple hormone deficiencies, the most frequent order of loss of anterior pituitary hormone function was GH, followed by LH/FSH, ACTH and then TSH.
Permanent radiation induced diabetes insipidus has not been reported 30,61. An explanation for the difference in radiosensitivity between the anterior and posterior pituitary lobe might be that the posterior lobe is only a storage place for hormones.