Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis

Objective Increased frequency of neuroimaging has led to enhanced identification of small non-functioning pituitary adenomas (NFPAs) leading, in many cases, to extensive follow-up. However, the value of ongoing monitoring of these incidental lesions remains unclear. The study aims to determine the need for surgical intervention and assess the risks of developing new endocrinopathies during follow-up in patients with conservatively treated micro-NFPAs. Design A systematic review and individual participant data meta-analysis. Methods We conducted a bibliographical search of PubMed and EMBASE to identify relevant studies. Authors of eligible studies were invited to share individual participant data. Cohort studies including patients with conservatively treated micro-NFPAs with at least one follow-up MRI were considered eligible. Fourteen studies met inclusion criteria. Six authors provided individual participant data (N=647). Data were re-analyzed for verification. In cases of discrepancies the original authors were contacted for authentication. Results Risk estimates were reported as number of events per 100 person-years (PYs). Estimates were pooled using the two-step approach. Overall probability of surgery was 0.2/100PYs (95%CI: 0.0 to 0.4; I2=28%). Probability of surgery due to visual impairment was 0.1/100PYs (95%CI: 0.0 to 0.2; I2=0%). Both were independent of baseline tumor size (≥6 mm or <6 mm), sex, or age (p-values>0.40). Risk of developing a new endocrinopathy was 1.0/100PYs (95%CI: 0.4 to 1.6; I2=0%). Data for classical meta-analysis were available for 7 studies (N=1089) and supported the individual participant data results. Conclusions These data suggest that routine follow-up of micro-NFPAs can be reduced significantly and that available guidelines should be revisited.