title: Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia.
abstract: BACKGROUND
  Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms.
  
  
  METHODS
  Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC).
  
  
  RESULTS
  Normative data for six prolactin assays included the range of values (2.5th-97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively.
  
  
  CONCLUSIONS
  Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.
authors.affiliation: .
authors.forename: Martin
authors.identifier: http://orcid.org/0000-0003-2277-590X
authors.initials: M
authors.lastname: Overgaard
authors.affiliation: .
authors.forename: Susanne Møller
authors.initials: SM
authors.lastname: Pedersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D011232:Chemical Precipitation; D016001:Confidence Intervals; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000175:diagnosis*; D007118:Immunoassay / Q000379:methods* / Q000592:standards*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry; D011388:Prolactin / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification / Q000592:standards; D015175:Prolactinoma / Q000175:diagnosis*; D011933:Reagent Kits, Diagnostic; D012016:Reference Values; D055815:Young Adult
chemical_list: D011933:Reagent Kits, Diagnostic; D011092:Polyethylene Glycols; D011388:Prolactin
keywords: assay interference; hyperprolactinemia; immunoassay; macroprolactinemia; polyethylene glycol precipitation; reference interval