Objective: Aggressive pituitary tumours may be difficult to treat. Temozolomide (TMZ) is an alkylating cytostaticum. In a small number of cases, TMZ therapy has been reported to reduce pituitary tumour size and hormone hypersecretion. Design: We present three patients with pituitary tumours treated with TMZ. One tumour was initially a macroprolactinoma that developed into a mixed GH-and prolactin-secreting carcinoma (patient A). To our knowledge, this is the first published in English literature. Two adenomas, a macroprolactinoma (patient B) and a clinically non-functioning pituitary adenoma (patient C), were highly invasive. The three patients suffered from extensive tumour mass effects, and all tumours were resistant to conventional treatment. Method: TMZ, 150-200 mg/m 2 of body surface area was administered orally for 5 days during each 28-day cycle. Result: During TMZ therapy, tumour sizes were significantly reduced, hormone levels normalized and symptoms of mass effects decreased in all three cases. The carcinoma was treated from 2004 to 2006 (23 months). Three years after the terminating treatment, the tumour has not regrown and hormone levels are normalized. Immunohistochemical staining for methylguanine DNA methyltransferase (MGMT) was negative in two patients (A and B), and in one patient (C) a few nuclei stained positive. Conclusion: TMZ therapy significantly decreased tumour volume, hormone hypersecretion and symptoms in all three patients, corresponding to the pathological findings regarding MGMT. TMZ therapy may be a new option for the treatment of resistant pituitary adenomas.

Objectives: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients with hyperprolactinaemia may develop clinical acromegaly. Methods: We have included patients examined at department M, Odense University Hospital between 1996 and 2001. Seventy-eight patients with prolactinomas, 65 females and 13 males, with a median age (range) of 30 years (14-74) and 47 years (20-66), respectively, were included in the study. Results: In females and males the median prolactin (PRL) levels were 90 mg/l (27 -4700; normal values (NV) #23) and 1075 mg/l (24-6500; NV # 14), respectively. The PRL levels were significantly higher in males compared with females (P , 0.002). Fifty-nine patients with acromegaly, 24 females and 35 males, with a median age (range) of 45 years (24-70) and 53 years (19 -70), respectively, were included. Seven of the 24 females had hyperprolactinaemia, with PRL levels of 90 mg/l (27-494). Thirteen of the 35 males had hyperprolactinaemia with PRL levels of 47 mg/l (17-251). Three females with prolactinomas developed acromegaly clinically and biochemically. These patients had a normal low GH level and/or a normal IGF-I level at first diagnosis. Conclusions: Our findings suggest that there is a common group of patients with a pituitary adenoma who secrete PRL and GH unsynchronously. Some of these patients have clinical acromegaly at diagnosis and some patients diagnosed as prolactinomas will develop acromegaly. We suggest an annual IGF-I measurement as a screening test.