Serum prolactin measurement is a routine test in several conditions in every day clinical practice, and the finding of hyperprolactinemia can induce complex and expensive imaging studies. Circulating prolactin is a heterogeneous hormone and, from a molecular weight point of view, there are three main forms: the 23kDa monomer, the 45kDa dimer (big prolactin) and the higher than 150kDa macroprolactin, or big-big prolactin. In normal conditions, or in patients with symptomatic hyperprolactinemia, the monomeric form is the predominant. Macroprolactin is constituted, in the majority of cases, by an association of prolactin and IgG that leads to a longer half-life and decreased biological activity. The most commonly employed method to screen for the presence of significant quantities of macroprolactin is the study of recovery after polyethylene glycol (PEG) precipitation, and the confirmation, if necessary, includes gel filtration chromatography. The cut-off values must be defined for each method, since the recognition of the different forms can vary between methods. The frequency of the finding of a predominance of macroprolactin in a patient with hyperprolactinemia varies in the literature, but is most commonly accepted to be around 25%. The importance of the finding of the phenomenon of predominance of macroprolactin is related to the fact that this molecular form of prolactin is supposed to have lower biological activity, is associated to asymptomatic or oligosymptomatic cases, and normal imaging studies. Consequently, in special in patients with clinical symptoms not characteristic, the screening for macroprolactin is essential. In positive cases, additional imaging studies should only be indicated in patients with clinical symptoms suspect of being a consequence of a pathological hyperprolactinemia.
Circulating prolactin forms; Macroprolactin; Hyperprolactinemia; PEG precipitation
