SummaryMacroprolactin 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.
Nature of macroprolactinHigh molecular weight nonbioactive isoforms of prolactin may be present in amounts which cause clinically misleading hyperprolactinaemia unless recognized. In the majority of subjects who have hyperprolactinaemia which is entirely accounted for by the presence of macroprolactin, macroprolactinaemia, the responsible isoform is approximately l50 kDa in weight and composed of a molecule of prolactin bound to an IgG molecule.1 Approximately 10% of macroprolactin has alternative compositions and sizes.1 These include aggregates of prolactin monomers with varying glycosylation and exhibiting covalent and noncovalent bonding and other isoforms. 2 The most usual isoform of macroprolactin causes hyperprolactinaemia because of the slow clearance rate of the prolactin-IgG complex rather than because of increased prolactin production. High levels of total prolactin have been found in otherwise entirely normal subjects without any of the symptoms associated with hyperprolactinaemia. Loss of bioactivity of prolactin on formation of macroprolactin can be predicted from alterations in tertiary structure and reduced availability because of retention of prolactin within the vascular tree, all associated with the binding of prolactin to IgG. However, when macroprolactin has been evaluated by the classical NB2 cell system for prolactin bioassay, activity has been consistently demonstrated. 3 It has now been shown that during incubation in this system dissociation of macroprolactin with the release of monomeric prolactin occurred which would account for the bioact...