Supplementary Material for: Endocrine function after transsphenoidal surgery in patients with non-functioning pituitary adenomas: A systematic review and meta-analysis

Introduction: Transsphenoidal surgery is the current treatment for mass reduction in patients with non-functional pituitary adenomas (NFPAs). The surgical procedure may deteriorate or recover pituitary endocrine function. The aim of this study was to systematically assess the benefits and harms of transsphenoidal surgery on pituitary endocrine function in patients with NFPAs. Methods: This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42020210853). We searched Pubmed and EMBASE for studies reporting on pituitary function before and after transsphenoidal surgery in patients with NFPAs having a minimum follow-up of one month. The pre-specified primary outcomes were the proportions of patients with improved or deteriorated pituitary function after surgery reported as weighted mean using random effects meta-analysis or in case of considerable heterogeneity, i.e. I2 ≥ 75%, as a range of reported proportions. Subgroup analyses was planned for the primary outcomes on study level. Results: Of the 6597 identified records, 24 studies enrolling 3816 participants were eligible for assessment. Twenty-three studies were judged to have serious or critical risk of bias. The range of proportions of patients with recovery of at least one pituitary axis was between 10.2 % and 97.7 % (I2= 93 %), while the range of proportions of patients experiencing loss of at least one axis after pituitary surgery was between 0.0 % and 36.6 % (I2= 91 %). Conclusions: The current systematic review finds that the endocrine effect of pituitary surgery is unclear both in terms of the chance of recovery and the risk of pituitary failure and hypopituitarism should be considered only a relative indication for surgery. However, the range of effects does include potentially clinically relevant rates of pituitary recovery calling for more systematic collection of data in future studies.