Radiotherapy in acromegaly: the argument against.

External pituitary irradiation (XRT) has been used as a therapeutic modality in patients with acromegaly for the past 100 years. Multiple studies have demonstrated the slow but inexorable decline of plasma GH for as long as 20–25 years after the procedure, with some 70 –90% of patients ultimately achieving plasma GH levels below 5 µ g/l (1 µ g = 2·6 mU). Also, XRT either shrinks pituitary tumours or, at the very least, effectively prevents them from enlarging. Thus, XRT offers both biochemical and morphological benefits to patients with acromegaly. However, the downside of XRT is not negligible. Up to 50 – 60% of patients develop hypopituitarism, and some have optic nerve damage or ophthalmoplegia. The ensuing cerebrovascular damage raises the risk of a cerebrovascular accident 2– 4-fold. Additionally, there is a small (1–2%) but devastating risk of developing radiation-induced malignant brain tumours, and the neurocognitive impairments (memory deficits, depression, etc.) appear to be significant. The morbidities of acromegaly (arthropathy, cardiomyopathy, sleep apnea, etc.) also continue to progress during the long interval between the procedure and the biochemical 'cure'. Despite these problems, the balance between the risks and benefits of XRT was clearly tilted towards the latter as long as surgical techniques remained crude and the pharmacological modalities nonexistent. Most importantly, the belief that GH levels below 5 –10 µ g / l were biologically harmless (Christy, 1982) implied that radiotherapy was a highly effective therapeutic modality. The development and wide availability of IGF-1 assays have changed the definition of what constitutes good control of acromegaly. On purely theoretical grounds, measurement of a trophic, instead of a target, hormone seems to be misplaced. Indeed, one would not claim 'cure' of Cushing's disease or a TSH-producing tumour based on 'normal' ACTH or TSH concentrations as long as cortisol or thyroxine levels remain elevated. Clinical manifestations of acromegaly correlate very well with plasma IGF-1 but very poorly with plasma GH (Clemmons et al ., 1979). Plasma IGF-1 remains elevated in 10 – 40% of the patients whose GH was decreased below 2–2·5 µ g / l (Barrande et al ., 2000; Peacey et al ., 2001), and the mortality in such patients is still increased by a similar percentage (Bates et al ., 1993; Orme et al ., 1998) despite statistical 'similarity' with the general population. Even newly diagnosed and clinically active patients may present with a full-blown clinical picture of acromegaly …