Side Effects Of Pituitary Irradiation

The damaging effects of radiation can result in neurologic damage, pituitary endocrine failure, second malignancy, and potential vascular effects.

Radiation damage to the optic nerves and optic chiasm in the form of radiation-induced optic neuropathy (delayed normal tissue damage) leads to impairment in visual acuity. After conventional fractionated external beam radiotherapy, the risk of optic radiation neuropathy is 0-2% (18,20,44). The largest series re ported a 1.5% risk of visual impairment not attributable to other recognized ophthalmologic causes (18), and most modern series report risk <1% (44).

Although there is fear of temporal lobe damage from radiation passing through normal tissues, where 3-field technique is routine, radiation doses to the temporal lobes are small and no cases of temporal lobe necrosis have been described in modern series. Studies using positron emission tomography (PET) imaging have also failed to demonstrate reduced uptake of fluor-2-deoxy-glucose (FDG) in the temporal lobes (45). Previously reported cases of temporal lobe damage are most likely owing to older radiation techniques using two opposing radiation beams.

There is anecdotal information on the potential damaging effect of pituitary irradiation on cognitive function. However, published cross-sectional data on patients with pituitary adenoma suggest mild dysfunction after surgery with or without radiotherapy, and the contribution to long-term cognitive impairment from radiation alone is not clear (46-48).

The most frequent complication of pituitary irradiation is pituitary endocrine deficiency. The reported sequence of deficiency after radiotherapy is GH deficiency followed by luteinizing hormone (LH)/follicle-stimulating hormone (FSH), adenocorticotropin hormone (ACTH), and thyroid-stimulating hormone (TSH) (49,50). Other authors report no clear difference in the timing of onset of endocrine deficiencies (51). The mechanism of endocrine dysfunction is considered to be hypothalamic damage, and this is largely based on evidence from patients who receive whole-brain irradiation (52). Deficiency in the release of pituitary hormones resulting from cellular depletion or other local injury within the pituitary gland may also play a role, because hypopituitarism has been reported after localized irradiation in the form of interstitial radiotherapy and radiosurgery. The risk of posterior pituitary failure after irradiation is negligible.

The likelihood of developing radiation-induced pituitary deficiency is partly determined by latent or preexisting pituitary dysfunction. In patients not requiring replacement therapy in the immediate postradiotherapy period, the actuarial cumulative probability of requiring hydrocortisone and thyroxine replacement therapy is 10-30% at 10 yr and 30-50% at 20 yr (after doses of 40-50 Gy in 25-30 fractions) (51 unpublished personal data). Other studies report rates of deficiency at 10 yr of approx 80% for ACTH and 30% for TSH, with a suggestion of faster decline in hormone levels after higher radiation doses (50). From a clinical perspective, regular assessment of pituitary function after radiotherapy is the primary medical activity in the posttreatment period.

Therapeutic radiation is a well-recognized predisposing factor to the development of second brain tumor. Radiation-induced brain tumors have been described after low-dose scalp irradiation for tinea capitis (53) and after prophylactic cranial irradiation in acute lymphocytic leukemia (ALL) in children (54,55). The risk of radiation-induced second brain tumor in patients with pituitary adenoma is 1-2% at 10 yr and 2-3% at 20 yr and may be in the form of radiation-induced meningioma, sarcoma, or a malignant glioma (43,56). The relative risk compared with the normal population is 10, with wide CIs because of the relatively small size of the patient populations studied. An unresolved issue is the individual contributions of radiation and potential predisposition to potential malignancy in patients with pituitary adenoma (57).

Patients with pituitary adenoma are at increased risk of cardiovascular and cerebrovascular events (37,42,58). Although this is partly caused by the metabolic consequences of hypopituitarism, it is likely that radiation-induced and possibly surgically induced vascular damage is a contributing factor (58). The magnitude of contribution to the overall risk from radiation is not defined.

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