Macroprolactinaemia: a biological diagnostic strategy from the study of 222 patients

Gel filtration chromatography (GFC), the gold standard for macroprolactinaemia (MPRL) diagnosis, is a slow, costly and labour-intensive method. To limit the number of GFC required, we evaluated two screening tests for MPRL: prolactin (PRL) recovery after polyethylene glycol (PEG) precipitation and PRL concentration ratio, derived from two assays, each having different big-big-PRL cross-reactivities.In some patients, MPRL is characterised by clinical symptoms which can be associated with an excess of monomeric PRL. We compared the monomeric PRL concentration obtained from GFC with the PRL concentration i) on a cobas e 601 analyser and ii) in the supernatant after PEG precipitation.

We studied hyperprolactinaemic sera subjected to physician-ordered GFC, between February 2013 and July 2014. We performed PEG precipitation (to evaluate the PRL concentration and rate of recovery in the supernatant) and two PRL assays: RIA and electrochemiluminescent assay (ECLIA), on a Roche cobas e 601 analyser, and calculated the RIA/ECLIA ratio.

Among the 222 sera, we were able to diagnose or exclude MPRL in 72.1% of cases, based solely on the ratio and/or recovery. In the remaining cases, GFC was necessary for making a diagnosis. Elevated monomeric PRL was present in 10.9% of macroprolactinaemic sera. In the case of MPRL, both PRL measurements on the cobas analyser and in the supernatant weakly correlated with monomeric PRL values obtained from GFC.

The combination of PEG and RIA/ECLIA ratio analysis reduced the number of necessary GFC. However, GFC is essential in MPRL cases to evaluate the monomeric PRL concentration.