CONTEXT: Cushing syndrome (CS) is associated with hippocampal atrophy and psychopathology.

OBJECTIVE: The primary objective of this systematic review was to assess hippocampal volume (HV) in patients with CS. The secondary objectives were to assess patients' cognitive functioning, depressive and anxiety symptoms, and quality of life.

DATA SOURCES: PubMed, Embase, Cochrane, LILACs, and Scopus databases were searched for relevant studies until 1 May 2019.

STUDY SELECTION: Case-control studies comparing patients with CS with healthy control subjects, or studies assessing patients with CS before and after surgery were included. The initial search resulted in 18 studies fulfilling the inclusion criteria.

DATA EXTRACTION: Data extraction regarding all outcomes was performed independently by two reviewers. Quality assessment was assessed with the Newcastle-Ottawa Scale for case-control studies.

DATA SYNTHESIS: Meta-analysis was performed using a random effect model. The right-side HV in patients with CS was reduced by a standard mean difference of 0.68 (95% CI, -1.12 to -0.24; P = 0.002; I2 = 0%) compared with healthy control subjects, but with no increase in HV after surgery. Patients had more depressive symptoms, impaired cognitive functions, and reduced health-related QoL (HRQoL), which all responded favorably to surgery. The data did not support the presence of anxiety in patients with CS.

CONCLUSION: An overall reduction of HV in patients with CS was not suggested by the study findings. However, most cognitive domains were significantly affected and responded favorably to surgery. Depressive symptoms and reduced HRQoL were present in patients with CS and improved after surgery.