Prolactin Results for Samples Containing Macroprolactin Are Method and Sample Dependent

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Abstract
Prolactin (PRL) exists in human serum in several molecular forms that can be identified by gel-filtration chromatography (GFC). The 23-kDa monomer is the predominant form in the general population, but other circulating species include the 50-kDa form (big PRL) and the 150- to 170-kDa macroprolactin (big big PRL) ( 1)( 2). The prevalence of macroprolactin in the general population is currently unknown, but this macromolecular form of PRL has been characterized as a complex of PRL with an IgG antibody ( 3) that has reduced bioactivity in vivo ( 4) and a variable reactivity with commercial immunoassays for PRL ( 4)( 5)( 6)( 7)( 8). Macroprolactin is cleared from the blood circulation more slowly than monomeric PRL, leading to an apparent hyperprolactinemia, depending on the immunoassay used for the measurement of PRL. Thus, identification of macroprolactin as a cause of high PRL in a patient sample is important because it can help resolve diagnostic confusion and avoid expensive pituitary imaging studies and inappropriate treatment ( 5). As a result of distribution of serum containing macroprolactin in the United Kingdom National External Quality Assessment Scheme, immunoassays for the measurement of PRL have been subdivided into three classes according to their reactivity with macroprolactin: low-, medium-, and high-reading methods ( 6).