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.