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.