The incidence of cerebrovascular accidents in patients with pituitary adenoma

Background and Purpose: Patients with pituitary adenomas are effectively tr eated with a combination of surgery, radiotherapy, and medical therapy. Nev ertheless, long-term studies suggest increased mortality that is independen t of tumor control, with cerebrovascular accidents (CVA) as the major contr ibuting cause. The purpose of this study was to define the frequency of CVA s in a cohort of patients with pituitary adenoma and identify potential pre disposing factors. Patients and Methods: A cohort of 331 United Kingdom (UK) residents with pi tuitary adenoma treated at the Royal Marsden Hospital (RMH) between 1962 an d 1986 was studied. The frequency of CVA was assessed from RMH and referrin g hospital records and clinicians, by postal questionnaire of referring hos pitals and general practitioners, and by examination of all death certifica tes. The data were analyzed by actuarial methods, and risk factors were ass essed by multivariate analysis. The data were compared to the incidence of CVA in the general population using a published UK population cohort. Results: Sixty-four of 331 patients developed CVA after primary treatment o f pituitary adenoma. The actuarial incidence of CVA was 4% (95% CI: 27%) at 5 years, 11% (95% CI: 8-14%) at 10 years, and 21% (95% CI: 16-28%) at 20 y ears measured from the date of radiotherapy. The relative risk of CVA compa red to the general population in the UK was 4.1. Age was an independent pre dictive factor for CVA. However, the relative risk in comparison to the gen eral population was independent of age. The relative risk of developing CVA was higher in women compared to men, in patients undergoing debulking surg ery compared to less radical procedures, and in patients diagnosed and trea ted in the 1980s compared to previous decades. The dose of radiotherapy was an additional independent prognostic factor on multivariate analysis. Conclusion: Patients with pituitary adenoma treated with surgery and radiot herapy have a significantly increased risk of CVA compared to the general p opulation. The factors which may contribute to the increased risk include t he presence of pituitary adenoma and consequent endocrine disturbances and the treatment, particularly the extent of surgery and the dose of radiother apy. When assessing the value of treatment strategies, it is therefore impo rtant to include not only intermediate endpoints of tumor and hormonal cont rol, but also late toxicity, including the incidence of CVA and overall sur vival as the primary endpoint. The potential predisposing factors for CVA n eed further elucidation to develop treatment strategies with lower risk and consequently, reduced mortality. (C) 1999 Elsevier Science Inc.