Should macroprolactin be measured in all hyperprolactinaemic sera?

Macroprolactin is a nonbioactive prolactin isoform usually composed of a monomer of prolactin and a IgG molecule which has a prolonged clearance rate similar to that of the immunoglobulins. Macroprolactinaemia, hyperprolactinaemia entirely accounted for by the presence of macroprolactin, is estimated to account for approximately 10% of all hyperprolactinaemia coming to clinical attention in the United Kingdom and the United States. Failure to recognize that macroprolactinaemia can explain hyperprolactinaemia, leads to unnecessary investigation, incorrect diagnosis and inappropriate treatment. Screening of hyperprolactinaemic sera for the presence of misleading concentrations of macroprolactin is readily performed in biochemistry laboratories although the procedures have not been automated. The most widely employed method is to treat the hyperprolactinaemic sera with polyethylene glycol which precipitates out high-molecular weight constituents including immunoglobulins. Re-assay of the sera for prolactin will then identify those sera which yield values within the relevant normal range indicative of macroprolactinaemia and not true hyperprolactinaemia. The case for the routine screening of all hyperprolactinaemic sera for macroprolactin is compelling. The consequences of failure to recognize macroprolactinaemia are significant, the problem is frequently encountered, the means of addressing it are immediately available and it is cost effective.