Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays

Macroprolactinemia, i.e. sustained hyperprolactinemia where the predominant circulating form of prolactin (PRL) is of large molecular weight, is a common phenomenon comprising up to one-fourth of all cases of hyperprolactinemia. We measured serum PRL levels by four different immunoassay systems (PROL-CTK, RIAgnost, Delfia, ACS 180) and by the Nb2 bioassay in patients with prolactinomas/idiopathic hyperprolactinemias in whom monomeric PRL was the major species of PRL (n=11, group 1) and in patients with macroprolactinemia (n=12, group 2). In group 1, the results obtained with the different immunoassays and with the Nb2 assay were highly correlated (r=0.945-0.982). On the other hand, big big-PRL (bb-PRL) was differently recognized by the immunoassays, since measured serum PRL values from each patient were highly variable in group 2. RIA-gnost Prolactin and Delfia Prolactin detected bb-PRL similarly and they were highly correlated with each other (r=0.937, p<0.0001). ACS 180 detected bb-PRL somewhat differently from the RIA-gnost and Delfia systems, but likewise most of the patients of group 2 had PRL values above normal. PROL-CTK was the method less influenced by the presence of bb-PRL since most of the subjects with macroprolactinemia had PRL levels either within the normal range or only marginally elevated. From the immunoassays tested, PROL-CTK was the system which was less correlated with the Nb2 bioassay in group 2 (r=0.252; NS). Our experience is that macroprolactinemia is an asymptomatic condition in most of the cases. Therefore, we suggest that the routine measurement of PRL should be done with methods that are only minimally affected by the presence of macroprolactin. Such an approach would obviate the use of extensive, frequently expensive and ultimately useless diagnostic tests that are needed to determine the cause of the hyperprolactinemia.