Optimal management of non-functioning pituitary adenomas

The long-term outcome of non-functioning pituitary adenoma (NFPA) patients is not clearly established, probably due to the low annual incidence and prolonged natural history of these rare tumors. The aim of this study was to evaluate clinical data at presentation and long-term post-surgery and radiotherapy outcome in a cohort of patients with NFPA. A computerized database was developed using Access 2000 software (Microsoft Corporation, 1999). Retrospective registration of 295 NFPA patients was performed in seven Endocrinological Centers of North West Italy. Data were analyzed by STATA software. The main presenting symptoms were visual defects (67.8%) and headache (41.4%) and the most frequent pituitary deficit was hypogonadism (43.3%), since almost all tumors were macroadenomas (96.5%). Surgery was the first choice treatment (98% of patients) and total debulking was achieved in 35.5%. Radiotherapy was performed as adjuvant therapy after surgery in 41% of patients. At the follow-up, recurrence occurred in 19.2% of patients without post-surgical residual tumor after 7.5 +/- 2.6 years, regrowth in 58.4% of patients with post-surgical remnant after 5.3 +/- 4.0 years and residue enlargement in 18.4% of patients post-surgically treated with radiotherapy after 8.1 +/- 7.3 years. Our database indicates that the goal of a definitive surgical cure has been achieved during the last decade in a low percentage of patients with NFPA. This tumor database may help to reduce the delay between symptom onset and diagnosis, to assess prognostic parameters for the follow-up of patients with different risk of recurrence and to define the efficacy and safety of different treatments and their association with mortality/morbidity.

We assessed the risk of second brain tumors in a cohort of patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. Four hundred and twenty-six patients (United Kingdom residents) with pituitary adenomas received radiotherapy at the Royal Marsden Hospital (RMH) between 1962 and 1994. They were followed up for 5749 person-years. The cumulative incidence of second intracranial tumors and systemic malignancy was compared with population incidence rates through the Thames Cancer Registry and the National Health Service Central Register (previously OPCS) to record death and the potential causes. Eleven patients developed a second brain tumor, including five meningiomas, four high grade astrocytomas, one meningeal sarcoma, and one primitive neuroectodermal tumor. The cumulative risk of second brain tumors was 2.0% [95% confidence interval (CI), 0.9-4.4%] at 10 yr and 2.4% (95% CI, 1.2-5.0%) at 20 yr, measured from the date of radiotherapy. The relative risk of second brain tumor compared with the incidence in the normal population was 10.5 (95% CI, 4.3-16.7). The relative risk was 7.0 for neuroepithelial and 24.3 for meningeal tumors. The relative risks were 24.2 (95% CI, 4.8-43.5), 2.9 (95% CI, 0-8.5), and 28.6 (95% CI, 0.6-56.6) during the intervals 5-9, 10-19, and more than 20 yr after radiotherapy (four cases occurred >20 yr after treatment). There was no evidence of excess risk of second systemic malignancy. An additional 10-yr update confirmed our previous report of an increased risk of second brain tumors in patients with pituitary adenoma treated with surgery and radiotherapy. The 2.4% risk at 20 yr remains low and should not preclude the use of radiotherapy as an effective treatment option. However, an increased risk of second brain tumors continues beyond 20 and 30 yr after treatment.

The natural history of non-functioning pituitary macroadenomas (NFMA) has not been completely elucidated. Therefore, we evaluated pituitary function, visual fields, and tumor size during long-term follow-up of non-operated patients with NFMA. Follow-up study. Twenty-eight patients (age 55 +/- 3 years) with NFMA, not operated after initial diagnosis, were included. Initial presentation was pituitary insufficiency in 44%, visual field defects in 14%, apoplexy in 14%, and chronic headache in 7% of the patients. The duration of follow-up was 85 +/- 13 months. Radiological evidence of tumor growth was observed in 14 out of 28 patients (50%) after duration of follow-up of 118 +/- 24 months. Six patients (21%) were operated, because tumor growth was accompanied by visual field defects. Visual impairments improved in all the cases after transsphenoidal surgery. Spontaneous reduction in tumor volume was observed in eight patients (29%). No independent predictors for increase or decrease in tumor volume could be found by regression analysis. Observation alone is a safe alternative for transsphenoidal surgery in selected NFMA patients, without the risk of irreversibly compromising visual function.