title: Nonsurgical cerebrospinal fluid rhinorrhea in invasive macroprolactinoma: incidence, radiological, and clinicopathological features.
abstract: BACKGROUND
  Macroprolactinomas (MPRLs) may result in nonsurgical (spontaneous or dopamine agonist induced) cerebrospinal fluid (CSF) rhinorrhea; however, the incidence of and mechanisms underlying this phenomenon are poorly understood.
  
  
  OBJECTIVE
  The objective of the study was to determine the incidence of nonsurgical rhinorrhea and identify biochemical, radiological, and histopathological factors associated with leakage.
  
  
  METHODS
  A retrospective review of MPRL patients (n = 114) was compared with patients with nonfunctioning pituitary adenoma (NFA) (n = 181) seen over a 19-yr period (1985-2004).
  
  
  METHODS
  Incidence of CSF rhinorrhea, factors predictive of leakage, and differential expression of candidate markers of invasiveness were measured.
  
  
  RESULTS
  Nonsurgical CSF rhinorrhea occurred in 8.7% of MPRLs (10 of 114) [2.6% spontaneous (three of 114), 6.1% dopamine agonist induced (seven of 114)], whereas no NFAs developed nonsurgical rhinorrhea. There was a clear male preponderance in MPRLs with nonsurgical rhinorrhea (males to females, 9:1, P = 0.008). Dopamine agonist resistance was more frequent in MPRLs with rhinorrhea than with MPRLs without rhinorrhea [30% (n = 10) vs. 5% (n = 104) P = 0.003]. Baseline prolactin levels, rate of prolactin decline in response to dopamine agonists, and tumor volume at diagnosis did not predict CSF leakage. Candidate markers of invasiveness, specifically the protease-activated receptor 1 and e-cadherin expression scores and tumor macrophage density, were not significantly different between groups; MPRL+CSF rhinorrhea (n = 6), MPRL without CSF rhinorrhea (n = 9), and NFAs (n = 9).
  
  
  CONCLUSIONS
  The incidence of nonsurgical CSF rhinorrhea in MPRL patients (8.7%) is higher than expected. Dopamine agonist resistance is more common in MPRLs with CSF rhinorrhea; however, whether this is a mechanistic relationship requires further study. Protease-activated receptor 1 expression, e-cadherin expression, and macrophage infiltration rates do not distinguish tumors with from those without CSF rhinorrhea.
authors.affiliation: Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Oxford OX3 7LJ, United Kingdom.
authors.forename: S G I
authors.initials: SG
authors.lastname: Suliman
authors.forename: A
authors.initials: A
authors.lastname: Gurlek
authors.forename: J V
authors.initials: JV
authors.lastname: Byrne
authors.forename: N
authors.initials: N
authors.lastname: Sullivan
authors.forename: G
authors.initials: G
authors.lastname: Thanabalasingham
authors.forename: S
authors.initials: S
authors.lastname: Cudlip
authors.forename: O
authors.initials: O
authors.lastname: Ansorge
authors.forename: J A H
authors.initials: JA
authors.lastname: Wass
mesh_terms: D000236:Adenoma / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002559:Cerebrospinal Fluid Rhinorrhea / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008264:Macrophages / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology*; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology*; D011859:Radiography; D044463:Receptor, PAR-1 / Q000378:metabolism; D012189:Retrospective Studies; D017678:Sex Distribution
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D044463:Receptor, PAR-1; D011388:Prolactin; D020780:Matrix Metalloproteinase 9