The incidence of cerebrovascular accidents in patients with pituitary adenoma

Patients with pituitary adenomas are effectively treated with a combination of surgery, radiotherapy, and medical therapy. Nevertheless, long-term studies suggest increased mortality that is independent of tumor control, with cerebrovascular accidents (CVA) as the major contributing cause. The purpose of this study was to define the frequency of CVAs in a cohort of patients with pituitary adenoma and identify potential predisposing factors.

A cohort of 331 United Kingdom (UK) residents with pituitary adenoma treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 was studied. The frequency of CVA was assessed from RMH and referring hospital records and clinicians, by postal questionnaire of referring hospitals and general practitioners, and by examination of all death certificates. The data were analyzed by actuarial methods, and risk factors were assessed by multivariate analysis. The data were compared to the incidence of CVA in the general population using a published UK population cohort.

Sixty-four of 331 patients developed CVA after primary treatment of pituitary adenoma. The actuarial incidence of CVA was 4% (95% CI: 2-7%) at 5 years, 11% (95% CI: 8-14%) at 10 years, and 21% (95% CI: 16-28%) at 20 years measured from the date of radiotherapy. The relative risk of CVA compared to the general population in the UK was 4.1. Age was an independent predictive factor for CVA. However, the relative risk in comparison to the general population was independent of age. The relative risk of developing CVA was higher in women compared to men, in patients undergoing debulking surgery compared to less radical procedures, and in patients diagnosed and treated in the 1980s compared to previous decades. The dose of radiotherapy was an additional independent prognostic factor on multivariate analysis.

Patients with pituitary adenoma treated with surgery and radiotherapy have a significantly increased risk of CVA compared to the general population. The factors which may contribute to the increased risk include the presence of pituitary adenoma and consequent endocrine disturbances and the treatment, particularly the extent of surgery and the dose of radiotherapy. When assessing the value of treatment strategies, it is therefore important to include not only intermediate endpoints of tumor and hormonal control, but also late toxicity, including the incidence of CVA and overall survival as the primary endpoint. The potential predisposing factors for CVA need further elucidation to develop treatment strategies with lower risk and consequently, reduced mortality.