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Specificity and Clinical Utility of Methods for the Detection of Macroprolactin

¹ Department of Investigative Endocrinology, St. Vincent’s University Hospital, Dublin, Ireland.
² The Conway Institute of Biomolecular and Biomedical Research, University College, Dublin, Ireland.
³ Department of Clinical Chemistry, Southend Hospital, Essex, United Kingdom.

^aAddress correspondence to this author at: Department of Investigative Endocrinology, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. Fax 353-1-209-4981; e-mail thomas.smith{at}ucd.ie.

Background: Increased serum concentrations of macroprolactin are a relatively common cause of misdiagnosis and mismanagement of hyperprolactinemic patients.

Methods: We studied sera from a cohort of 42 patients whose biochemical hyperprolactinemia was explained entirely by macroprolactin. Using 5 pretreatments, polyethylene glycol (PEG), protein A (PA), protein G (PG), anti-human IgG (anti-hIgG), and ultrafiltration (UF), to deplete macroprolactin from sera before immunoassay, we compared residual prolactin concentrations with monomer concentrations obtained by gel-filtration chromatography (GFC). A monomeric prolactin standard was used to assess recovery and specificity of the pretreatment procedures.

Results: Residual prolactin concentrations in all pretreated sera differed significantly (P <0.001) from monomeric concentrations obtained after GFC. PEG underestimated (mean, 75%), whereas PA, PG, anti-hIgG, and UF overestimated (means, 178%, 151%, 178%, and 112%, respectively) the amount of monomer present. Of the 5 methods examined, PEG correlated best with GFC (r = 0.80) followed by PG (r = 0.78), PA (r = 0.72), anti-hIgG (r = 0.70), and UF (r = 0.61). After UF or pretreatment with anti-hIgG or PEG, recovery of monomeric prolactin standard was low: 60%, 85%, and 77% respectively. In contrast, pretreatment with PA or PG gave almost quantitative recovery.

Conclusions: None of the methods examined yielded results identical to the GFC method. PEG pretreatment yielded results that correlated best and is recommended as the first-choice alternative to GFC.

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