title: Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition.
abstract: OBJECTIVE
  The clinical characteristics and natural history of macroprolactinaemia are yet to be fully established and there is currently no widely accepted simple in vitro test for routine identification of the condition. This study was designed to further validate the polyethylene glycol (PEG) precipitation test with assessment of percentage prolactin recovery (%R), for the detection of macroprolactinaemia and clinically characterize cases identified using the test.
  
  
  METHODS
  Analytical validation and application of the PEG precipitation test for diagnosis of macroprolactinaemia and a retrospective case-notes review of some of the patients identified with the condition.
  
  
  METHODS
  Sera from 188 patients with elevated serum prolactin (PRL) concentrations were screened for macroprolactinaemia. Seventeen of the patients who were under follow-up at the local teaching hospital and were identified to have macroprolactinaemia were systematically characterized clinically.
  
  
  METHODS
  Prolactin was measured in sera, fractions from gel filtration chromatography and supernatant obtained after PEG precipitation, by the DELFIA fluoroimmunoassay. CLINICAL ENDPOINTS: Initial serum PRL and symptoms and their response to dopamine agonist therapy; imaging of the pituitary gland; serum PRL and symptoms after cessation of dopamine agonist therapy; course of serum PRL and symptoms without dopamine agonist therapy.
  
  
  RESULTS
  The within-batch coefficient of variation (CV) of the PEG precipitation test ranged between 2.8 and 7.3% while the between-batch CV ranged between 3.4 and 9.7%. Intra-individual variability up to five months was 9.9%. A prolactin recovery </= 40% was indicative of macroprolactinaemia, while the condition was unlikely to be present at values > 50%. The prevalence of macroprolactinaemia was 15% without sex difference. Clinical characterization of 17 patients showed modest initial serum PRL concentrations and there was imaging evidence of a coexisting pituitary adenoma in three of them. Dopamine agonist therapy resulted in substantial falls in serum PRL and this was associated with improvement or resolution of symptoms in some patients. Stoppage of dopamine agonist resulted in rebound hyperprolactinaemia in all cases. Spontaneous improvement in symptoms occurred in three patients but hyperprolactinaemia persisted in all those who were not on treatment.
  
  
  CONCLUSIONS
  The PEG precipitation test with assessment of 'free' prolactin has been shown to be reproducible and sensitive for the detection of macroprolactinaemia. Many of the patients who had macroprolactinaemia presented with at least one symptom of the hyperprolactinaemic syndrome. Dopaminergic therapy may influence the course of both serum PRL and symptoms in some of these patients.
authors.affiliation: Department of Clinical Biochemistry, Hope Hospital, Salford, Manchester, UK. AOlukoga@hotmail.com
authors.forename: A O
authors.initials: AO
authors.lastname: Olukoga
authors.forename: J W
authors.initials: JW
authors.lastname: Kane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002850:Chromatography, Gel; D005260:Female; D015200:Fluoroimmunoassay; D005590:Fractional Precipitation; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011237:Predictive Value of Tests; D011388:Prolactin / Q000097:blood*; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C060678:prolactin, polymeric; D011092:Polyethylene Glycols; D011388:Prolactin