A Dysexecutive Syndrome in Pituitary Disease: A Comprehensive Systematic Review and Meta-Analysis

Abstract Objective: Pituitary disease is a significant but often underrecognized cause of neuropsychological morbidity. Although cognitive impairment has been documented across subtypes, the specific pattern and persistence of deficits remain incompletely defined. This systematic review and meta-analysis aimed to (a) quantify baseline cognitive impairment in untreated pituitary disease, (b) characterize domain-specific impairment patterns, and (c) examine persistence following treatment. Method: A systematic search of PubMed/MEDLINE, PsycINFO, Web of Science, Scopus, and CINAHL was conducted in May 2024 and updated in June 2025. Following pre-registered criteria, 61 studies comprising 75 cohorts (2,879 patients, 1,513 controls) were included. Methodological quality was evaluated using a framework adapted from the Cochrane Risk of Bias tool. Random-effects meta-analyses and multilevel meta-regressions examined baseline impairment, domain-specific differences, subtype effects, and post-treatment outcomes. Results: Cognitive impairment was consistently observed across pituitary disease subtypes, particularly in memory, executive functioning, attention, and processing speed, with persistent deficits reported in 87.5% of post-treatment studies. Meta-analysis demonstrated significant baseline impairment relative to controls (g = −0.67, 95% CI [−0.89, −0.44], p