Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms.

Background: Macroprolactin is an important source of immunoassay interference that commonly leads to misdiagnosis and mismanagement of hyperprolactinemic patients. We used the predominant immunoassay platforms for prolactin to assay serum samples treated with polyethylene glycol (PEG) and establish and validate reference intervals for total and monomeric prolactin.

Methods: We used the Architect (Abbott), ADVIA Centaur and Immulite (Siemens Diagnostics), Access (Beckman Coulter), Elecsys (Roche Diagnostics), and AIA (Tosoh) analyzers with samples from healthy males (n = 53) and females (n = 93) to derive parametric reference intervals for total and post-PEG monomeric prolactin.

Technology insight: measuring prolactin in clinical samples.

Measurement of prolactin is one of the most commonly undertaken hormonal investigations in evaluating patients with reproductive disorders. Hyperprolactinemia is found in up to 17% of such cases. Diagnostic evaluation of hyperprolactinemia is difficult but is facilitated by a logical approach where a thorough patient history is obtained, secondary causes of hyperprolactinemia are excluded, and the limitations of current prolactin assays are appreciated.

Specificity and clinical utility of methods for the detection of macroprolactin.

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).