Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay

Objective: To examine whether use of the Beckman Coulter Access Prolactin (PRL) assay, which has low reactivity with macro-PRL, obviates the need for screening hyperprolactinemic samples. Design and methods: Samples from 1020 hyperprolactinemic individuals and 401 healthy volunteers were treated with polyethylene glycol (PEG). Macro-PRL was assessed from (1) percent PRL recovery, using cut-off values derived by gel filtration chromatography (GFC) and (2) significant (p < 0.05) normalisation of PRL following PEG. Results: PRL recovery was similar in volunteer and hyperprolactinemic samples (mean SD 101 +/- 13% and 101 +/- 19%, respectively). In hyperprolactinemic samples, macro-PRL was identified from PRL recovery in 9.7%, although levels were moderate to high in only 3.9%. The total PRL normalised following PEG in 7.4%. Correlations of PRL recovery with the proportions of macro-, big- and monomeric PRL following GFC (n=30 samples, range of PRL and macro-PRL levels) were -0.89, -0.20 and 0.92, respectively. The big-PRL content was 0-28%. Regression analysis suggested that PEG precipitated both macro-PRL and big-PRL. Conclusions: Using the Access assay, macro-PRL can cause apparent hyperprolactinemia and big-PRL may cause misclassification of individuals. Screening using PEG is applicable to assays with low macro-PRL reactivity provided specific reference values are derived. (c) 2006 The Canadian Society of Clinical Chemists. All rights reserved.