The Clinical Significance and Utility of Routine Screening for Macroprolactin in Patients With Hyperprolactinemia

Background: Macroprolactin is a complex of monomeric prolactin (PRL) molecules with immunoglobulin G (IgG) that can result in the elevation of serum prolactin level. Macroprolactin is biologically less active and failure to screen for macroprolactin may lead to unnecessary investigations and treatments in patients with hyperprolactinaemia. Aim: We sought to evaluate the clinical significance and clinical utility of routine screening of macroprolactin in patients with hyperprolactinemia. Methods: We analysed 141 patients from a retrospective database of patients with elevated serum prolactin in Changi General Hospital from Jan 2017 to Dec 2019 with routine screening of macroprolactin with polyethylene glycol (PEG) precipitation using Abbott Architect Prolactin assay. Clinical, biochemical, radiological data and medication usage were extracted from electronic medical records. Macroprolactinaemia was defined as a PRL recovery of < 60%. Approval was obtained from the local research ethics committee. Results: Thirty-six (26%) patients had macroprolactinaemia with a male predominance (72%). There were no significant differences in the presence of symptoms, the percentages of medication-induced hyperprolactinemia, and magnetic resonance imaging (MRI) pituitary scans done between patients with macroprolactinaemia and those with truly elevated serum prolactin. As such clinical features might not be useful to differentiate patients with macroprolactinaemia. Eight MRI pituitary scans were performed in patients with macroprolactinaemia and pituitary abnormalities were detected in 4 of the patients which are likely non-functioning pituitary lesions. As such, not only were unnecessary scans done but it also led to a cascade of further investigations. Eight patients had simultaneous macroprolactinaemia and elevated bioactive serum prolactin, as such post-PEG prolactin level with corresponding reference ranges rather than the percentage recovery should be use as the threshold for defining macroprolactinaemia to avoid misdiagnosis. Conclusion: Macroprolactinaemia is common and routine screening may avert unnecessary investigations. Post-PEG prolactin level with corresponding reference ranges should be used as diagnostic threshold.