Endocrine Abstracts

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 high tendency to recur; recurrence 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 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.

Only around 0.2% of pituitary tumours are carcinomas, as defined by the presence of intra- or extra-cranial metastases, but these offer an exceptional challenge. The majority of these tumours are either prolactin- or ACTH-secreting tumours, and it is interesting that non-functioning and somatotroph adenomas show evidence of ‘senescence’ markers, which are absent in ACTH- and prolactin-secreting adenomas. Patients with carcinomas may occasionally respond to dopamine- or somatostatin-receptor agonists, but in general require repeated transsphenoidal or even transcranial surgery. Conventional chemotherapy is generally ineffective, but recent reports with the alkylating agent temozolomide have shown cases of impressive tumour control, at least in the short term. The enzyme MGMT reverses the effect of temozolomide by removing the methyl adduct from DNA, and reports suggest that tumours lacking MGMT are especially sensitive to temozolomide. However, an extensive study has shown that only some 15% of pituitary adenomas lack MGMT, and it is probably reasonable to consider temozolomide therapy for 3–6 months regardless of MGMT status, which is in any case difficult to quantify. In theory, tumours which remain progressive following temozolomide may respond to everolimus, an mTOR inhibitor, but data on this are scanty.