Macroprolactin

Macroprolactin is a physiologically inactive form of prolactin found in a small proportion of people. It is in fact prolactin bound to IgG.

Macroprolactin, also conventionally known as “big-big prolactin”, refers to the presence of marked hyperprolactinemia associated with evidence of prolactin-IgG (typically IgG4) circulating complexes displaying a molecular weight of approximately 150 kDa (which is hence 6–7 fold higher that the native molecule) or, less frequently, polymeric aggregate of highly glycosylated prolactin monomers or prolactin-IgA complexes (i.e. non-IgG-type macroprolactin)[1]

In patients with hyperprolactinemia, the serum pattern of prolactin isoforms usually encompasses 60%–90% monomeric prolactin, 15%–30% big-prolactin and 0%–10% big-big prolactin[2]

The condition of macroprolactinaemia is hence defined as predominance (i.e. >30%–60%) of circulating prolactin isoforms with molecular weight >100 kDa[3]

Macroprolactin is important, as some laboratory assays will detect it as prolactin, leading to a falsely elevated prolactin result. This can lead to a misdiagnosis of hyperprolactinaemia in some people, especially those with other symptoms, such as infertility[4] or menstrual problems.

There are certain chemicals, such as polyethylene glycol, that can be added to remove macroprolactin from a suspicious sample. The sample can then be re-analysed to see if the prolactin levels are still high.The gold standard test to diagnose macroprolactin is gel-filtration chromatography.