The second line of therapy is pituitary irradiation with 4500 to 5000 cGy (rad), administered in daily fractions of 180 cGy, delivered during a period of 6 wk. This type of pituitary radiation involves an external beam irradiation from a high-energy linear accelerator.
Radiation delivery can also be achieved by high-voltage cobalt-60 particle irradiation, heavy particle beam radiotherapy, and stereotactic radiosurgery. Primary radiotherapy results in CD remission in up to 85% of patients (105,106). Hypercortisolism in these patients may persist up to 3 yr after radiation before a decline to normal cortisol levels can be seen. Radiation in association with mitotane therapy (o-p 'DDD), can produce a remission rate of approx 80% in the first year (107). This can increase further in the second year, but the sustained remission rate after discontinuing mitotane therapy drops significantly to less than 60% of the patients. Mitotane can be discontinued after 1 yr, if UFC has normalized. It can be reinitiated if hypercortisolemia recurs. By 3 yr, 80% to 90% of patients will have achieved biochemical remission of CS and will no longer need mitotane, because the effects of irradiation become established. If mitotane therapy is not tolerated by or fails to cure the patient, the final line of treatment is bilateral open or laparascopic adrenalectomy (108). This procedure is uniformly effective at the expense, however, of a commitment to hormone replacement for life, and a significant risk (10%—15%) for subsequent development of Nelson's syndrome (109-111).
Proton beam pituitary radiotherapy (12,000-14,000 rad) exposes the hypothalamus only to approx 500 rad, and thus rarely leads to anterior pituitary hormone deficiencies (105). Gamma Knife radiosurgery (gamma irradiation from cobalt-60 administered stereotactically in a single dose) may achieve long-term remission rates of 82% after multiple treatments (103,112). Approx 20% of patients develop pituitary insufficiency requiring hormone replacement therapy. If there is no chiasmal involvement and the adenoma is intrasellar, Gamma Knife radiosurgery may be an alternative treatment to conventional radiotherapy (113-115).
Radiotherapy usually is used in patients with persistent or recurrent CD after pituitary surgery. For patients with microadenomas treated with second-line radiotherapy, the remission rate at 3-yr follow-up can be up to 80% (103,106,115,116). For patients with macroadenomas, the response to radiotherapy is less favorable. In children, radiotherapy usually is rarely necessary and is more problematic than in adults, given the special need of pituitary hormones during the prepubertal and pubertal periods.
Long-term complications of (conventional) pituitary radiotherapy include hypopituitarism, memory deficits, brain necrosis, optic nerve or optic chiasm injury, and carcinogenesis (117,118) (and Chapter 13). When surgery and radiotherapy are combined, hypopituitarism may occur in as many as 50% of patients during a 10-yr period (119,120). At 8 year follow-up, the incidence of deficiencies in TSH, ACTH, gonadotropins, and growth hormone was 49%, 84%, 96%, and 100%, respectively (117). Therefore, patients who undergo pituitary radiotherapy need lifelong follow-up with routine testing for hypopituitarism and CD recurrence. Such testing should include periodic MRI brain/pituitary scanning and visual field testing.
Was this article helpful?