Pituitary tumours have recently been shown to have a prevalence of around one in a 1000, but the overwhelming majority of these are benign and readily treated. Nevertheless, while the initial therapy of the majority of non-secreting macroadenomas is transsphenoidal surgery, these have a tendency to recur even when apparently totally removed. Recurrence seems not to depend on dural invasion, and it cannot at present be predicted by any histopathological markers. Indeed, some 50% of such adenomas will recur over 10 years, although this recurrence rate is reduced to <5% with standard 3-portal conformal external beam radiotherapy. Such radiotherapy, while highly effective, does carry the risk of progressive hypopituitarism, but the risk of second tumour development or of visual path abnormalities is very low. Nevertheless, there may be an increased risk of cerebrovascular disease, and it would be extremely helpful to be able to predict which patients would benefit from this treatment. Radiosurgery appears to be a useful alternative where the recurrence is limited in size and is >5 mm from the optic chiasm ad nerves, although claims of an increased rate of effectiveness have not been easy to substantiate.
Only around 0.2% of pituitary tumours are carcinomas, as defined by the presence of intra- or extra-cranial metatsases, but these offer an exceptional challenge. The majority of these tumours are either prolactin- or ACTH-secreting tumours. Such patients may occasionally respond to dopamine- or somatostatin-recepor agonists, but in general require repeated transsphenoidal or even transcranial surgery. Conventional chemotherapy has not been shown to be particularly effective, but recent case reports with the alkylating agent temozolomide have shown scattered cases of impressive tumour control, at least in the short and medium term. The enzyme MGMT reverses the effect of temozolomide by removing the methyl adduct from DNA, and recent reports suggest that tumours lacking MGMT are especially sensitive to temozolomide. In such tumours there is evidence for methylation of the MGMT gene promoter. However, an extensive study has shown that only some 15% of pituitary adenomas lack MGMT, although this proportion may be higher in prolactinomas.
25 - 29 Apr 2009
European Society of Endocrinology