The natural history of non-functioning pituitary adenomas: A meta-analysis of conservatively managed tumors

Background: Non-functioning pituitary adenomas (NFPA) are often discovered incidentally. The natural history of NFPA is not well understood, obfuscating evidence-based management decisions. Meta-data of radiographically followed NFPA may help guide conservative versus operative treatment of these tumors. Methods: We searched PubMed, Medline, Embase, and Ovid for studies with NFPA managed nonoperatively with radiographic follow-up. Studies on postoperative outcomes after NFPA resection and studies that did not delineate NFPA data from functional pituitary lesions were excluded. NFPA were divided into micro- and macroadenomas based on size at presentation. We performed a meta-analysis of aggregate data for length of follow-up, change in tumor size, rate of apoplexy, and need for resection during follow-up. Results: Our database search yielded 1787 articles, of which 19 were included for final analysis. The studies included 1057 patients with NFPA followed radiographically. Macroadenomas were significantly more likely to undergo growth (34% vs. 12%; p < 0.01) or apoplexy (5% vs. < 1%; p = 0.01) compared to microadenomas. Resection was performed in 11% of all NFPA patients during follow-up regardless of size at presentation. Meta-regression showed that surgery during follow-up was associated with macroadenomas and negatively associated with microadenomas that decreased in size. Conclusion: Low-quality evidence suggests that NFPA classified as macroadenomas have an increased rate of growth and apoplexy during follow-up compared to microadenomas. A significant minority of all NFPA patients ultimately underwent surgery. In select patients, nonoperative management may be the appropriate strategy for NFPA. Macroadenomas may require closer follow-up.