Comparative assessment of cross-reactivity with Big-prolactin and macroprolactin in five commercial assays for prolactin

OBJECTIVES: Cross-reactivity with high molecular-weight (MW) macroprolactin in prolactin (PRL) immunoassays has been the subject of numerous studies. In contrast, little data are available regarding Big-PRL, a 50-60 kDa PRL isoform. METHODS: The immunoreactivity of Big-PRL was evaluated on five platforms (Alinity (Abbott), DxI 800 (Beckman Coulter), Liaison XL (DiaSorin), Kryptor compact plus (Thermo Scientific), and iSYS (IDS Immunodiagnostic Systems)) using 10 serum samples characterized by gel filtration chromatography (GFC) and containing between 17 and 80 % of Big-PRL. The spread of the results as a function of Big-PRL percentage was determined. Bland Altman bias between assays was calculated using a panel of GFC-characterised sera containing macroprolactin (n=46) or monomeric PRL (n=45). RESULTS: The Big-PRL samples were obtained from nonpregnant women, seven of whom had galactorrhea or oligospaniomenorrhea. All assays recognized Big-PRL in undiluted serum but to a variable extent. The spread of total PRL values correlated positively with Big-PRL percentage (r=0.954, p<0.0001). In samples containing >70 % Big-PRL, the methods ranked in the same order of recognition as that observed with macroprolactin-rich samples. Big-PRL was strongly detected by Alinity and iSYS whereas Kryptor and DxI were less sensitive to Big-PRL, as observed with macroprolactin. Consequently, the risk of false diagnosis of hyperprolactinemia tended to be lower with these two last assays. CONCLUSIONS: All five immunoassay platforms recognize the Big-PRL component in serum but to a variable extent. A high proportion of Big-PRL, combined with the use of a highly cross-reactive assay, may cause a false diagnosis of hyperprolactinemia.