Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin

BackgroundMacroprolactin is a large, heterogeneous form of prolactin with limited bioavailability. Detection of macroprolactin by different immunoassays varies widely. The objectives of this study were to determine the immunoreactivity of macroprolactin by the Ortho Clinical Diagnostics Vitros® ECi prolactin immunoassay, establish the most effective method for interpreting the prolactin concentration after PEG-precipitation, and correlate the clinical features of hyperprolactinemia with the presence of macroprolactin.MethodsPEG-precipitation was performed on 120 hyperprolactinemic specimens. Of these, 31 specimens with a recovery < 80% were fractionated by GFC. Four different approaches for identifying true hyperprolactinemia were investigated. Clinical symptoms of hyperprolactinemia were determined by chart review.ResultsMacroprolactin was detected by the Vitros ECi prolactin immunoassay. Use of a PEG modified prolactin reference interval was effective for identifying hyperprolactinemia in the presence of macroprolactin. There was no difference in the prevalence of abnormal menses, galactorrhea, or abnormal MRI between those with and without macroprolactin (p > 0.05). Accounting for macroprolactin in patients with hyperprolactinemia reduced the number of idiopathic cases.ConclusionsThe Vitros ECi prolactin immunoassay detects macroprolactin. PEG-precipitation is an acceptable surrogate to detect hyperprolactinemia in the presence of macroprolactin when using a prolactin reference interval derived from PEG precipitated reference sera. Although testing for macroprolactin should not substitute for standard evaluation of hyperprolactinemia, identification of macroprolactin may clarify a diagnosis and direct appropriate therapy.