Gross Variability in the Detection of Prolactin in Sera Containing Big Big Prolactin (Macroprolactin) by Commercial Immunoassays

Abstract A high molecular mass form of prolactin (PRL), macroprolactin, accumulates in the sera of some subjects. Although macroprolactin exhibits limited bioactivity in vivo, it retains immunoreactivity. We examined the frequency of macroprolactinemia in clinical practice and the ability of immunoassay systems to distinguish between macroprolactin and monomeric PRL. Of 300 hyperprolactinemic sera identified, 71 normalized following treatment of sera with polyethylene glycol, indicating that 24% of hyperprolactinemia could be accounted for by macroprolactin. Ten of these macroprolactinemic sera were circulated to 18 clinical laboratories. Two sets of PRL measurements of the 10 untreated sera were obtained from each of the nine most commonly used immunoassay systems. Across the nine assay systems, differences in the PRL estimates ranged from 2.3- to 7.8-fold. Elecsys users reported the highest PRL levels. Somewhat lower values were reported for DELFIA systems followed by Immuno-1, AxSYM, and Architect assays. The Immulite 2000 assay generated PRL levels equivalent to approximately 50% of those reported by the high-reading methods. The lowest PRL levels were reported by Access, ACS:180, and Centaur systems. To avoid confusion caused by the frequent presence of macroprolactin accounting for hyperprolactinemia, secondary screening for the presence of macroprolactin is recommended.