title: Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis.
abstract: BACKGROUND
  The natural history of pituitary incidentalomas (PIs) and nonfunctioning pituitary adenomas (NFPAs) remains poorly understood.
  
  
  OBJECTIVE
  The objective of the study was to synthesize the literature on the prognostic factors involved in the progression of PIs and NFPAs in patients followed up conservatively.
  
  
  METHODS
  We searched MEDLINE, EMBASE, and Cochrane CENTRAL. We sought to identify further studies by reviewing the reference lists from selected studies and reviews and by querying experts.
  
  
  METHODS
  Eligible studies were longitudinal observational cohort studies that enrolled patients with PIs/NFPAs and followed them up without any treatment from the time of detection and reported on mortality, lesion progression, and development of pituitary hormonal deficiency, apoplexy, or visual field defects.
  
  
  METHODS
  Reviewers working independently and in duplicate determined studies' eligibility and collected descriptive, methodological quality, and outcome data. Event rates per 100 person-years (PYs) and associated 95% confidence intervals (CIs) were estimated from each study and pooled using the random-effects model.
  
  
  RESULTS
  The 11 included studies had noncomparative single-cohort design. Follow-up duration ranged from 3 to 15 yr. There was a greater tendency for tumor growth in macroadenomas (12.5 per 100 PYs; 95% CI 7.9, 17.2) and in solid lesions (5.7 per 100 PYs; 95% CI 2.3, 9.2) in comparison with microadenomas (3.3 per 100 PYs; 95% CI 2.1, 4.5) and cystic lesions (0.05 per 100 PYs; 95% CI 0.0, 0.2). The development of pituitary apoplexy and worsening of visual field defects were rare. The overall incidence of new endocrine dysfunction was 2.4 per 100 PYs; 95% CI 0.0, 6.4. The majority of these analyses were associated with significant heterogeneity. There was a trend that did not reach statistical significance for greater incidence of pituitary apoplexy and new endocrine dysfunction worsening in macroadenomas compared with microadenomas. The quality of the evidence (risk of bias) was very low due to heterogeneity, methodological limitations, and imprecision caused by the small number of events.
  
  
  CONCLUSIONS
  Despite the relatively high prevalence of PIs/NFPAs, the evidence on the natural history of these entities is scarce and of low quality. PIs/NFPAs seem to have fairly rare complications that may be more common when lesions are large (>10 mm) and solid.
authors.affiliation: M.P.H., Mayo Clinic, The Knowledge and Encounter Research Unit, 200 First Street SW, Rochester, Minnesota 55905. murad.mohammad@mayo.edu.
authors.forename: M Mercè
authors.initials: MM
authors.lastname: Fernández-Balsells
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
authors.forename: Amelia
authors.initials: A
authors.lastname: Barwise
authors.forename: Juan F
authors.initials: JF
authors.lastname: Gallegos-Orozco
authors.forename: Anu
authors.initials: A
authors.lastname: Paul
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Lane
authors.forename: Julianna F
authors.initials: JF
authors.lastname: Lampropulos
authors.forename: Inés
authors.initials: I
authors.lastname: Natividad
authors.forename: Lilisbeth
authors.initials: L
authors.lastname: Perestelo-Pérez
authors.forename: Paula G
authors.initials: PG
authors.lastname: Ponce de León-Lovatón
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: Jantey
authors.initials: J
authors.lastname: Carey
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
mesh_terms: D000236:Adenoma / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D000465:Algorithms; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D033162:Incidental Findings; D010911:Pituitary Neoplasms / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*