Pituitary tumours are usually benign, but aggressive local growth may occur. Malignancy with demonstrable extracranial metastases is rarely seen. Tumour formation is probably the result of genetic changes involving tumour suppressor gene inactivation and oncogene activation. Pituitary adenomas that occur in a familial setting account for 45% of the tumours, they can be part of endocrine-related tumour syndromes. In 2006, Vierimaa et al.1 reported the results of a comprehensive genetic study that identified mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene as being associated with the familial presentation of somatotropinomas and prolactinomas. Prolactinomas are the most frequent pituitary adenomas in adolescents as well as adults. It is important to consider possible macroprolactinaemia, when prolactin measurements are performed. Usually macroprolactin consists of a monomer of prolactin and IgG, macroprolactin is not bioactive. The impact of failure to recognize macroprolactinaemia is significant. There can be no doubt that the diagnosis of acromegaly is often delayed and even overlooked. GH-hypersecretion may, however, rarely be found in patients with known pituitary adenomas, clinically silent or in prolactinomas.
Temozolomide is the first chemotherapeutic agent to show substantial response rates in aggressive pituitary tumours. Temozolomide is an alcylating agent with great ability to cross the bloodbrain barrier, it was first used for malignant gliomas. The lesion at O6-guanine is the critical methyl adduct produced by temozolomide and responsible for the greatest cytotoxicity. This lesion is repaired in the presence of O6-methylguanine-DNA methyltransferase (MGMT). Future studies will evaluate the role of temozolomide in the management of benign aggressive pituitary adenomas.
(1) Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 312 (5777) 122830, 2006.
Declaration of interest: The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.