Determination of prolactin: The macroprolactin problem

Serum prolactin is frequently measured when investigating patients with reproductive disorders and elevated concentrations are found in up to 17% of such cases. Clinical laboratories rely predominantly on automated analysers to quantify prolactin levels using sandwich immunometric methodologies. Though generally robust and reliable, such immunoassays are susceptible to interference from a high molecular mass prolactin/IgG autoantibody complex termed macroprolactin. While macroprolactin remains reactive to varying degrees in all prolactin immunoassays, it exhibits little if any biological activity in vivo and consequently its presence is considered clinically irrelevant. Macroprolactinaemia, defined as hyperprolactinaemia due to excess macroprolactin with normal concentrations of bioactive monomeric prolactin, may lead to misdiagnosis and mismanagement of hyperprolactinemic patients if not recognised. Current best practice recommends that all sera with elevated total prolactin concentrations are sub-fractionated using polyethylene glycol precipitation to provide a more meaningful clinical measurement of the bioactive monomeric prolactin content. Manufacturers of prolactin assays should strive to minimise interference from macroprolactin in their assays. Clinical laboratories should introduce screening procedures to exclude macroprolactinaemia in all patients identified as having hyperprolactinaemia. Clinicians should be aware of this potential diagnostic pit fall and insist on PEG screening of all hyperprolactinaemic sera.