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Licensed Unlicensed Requires Authentication Published by De Gruyter June 15, 2022

Interference by macroprolactin in assays for prolactin: will the In Vitro Diagnostics Regulation lead to a solution at last?

  • Michael N. Fahie-Wilson EMAIL logo , Christa M. Cobbaert , Andrea R. Horvath and Thomas P. Smith

Abstract

Cross reactivity with high molecular weight complexes of prolactin known as macroprolactin is a common cause of positive interference in assays for serum prolactin. All prolactin assays currently available are affected with 5–25% of results indicating hyperprolactinaemia falsely elevated due to macroprolactinaemia – hyperprolactinaemia due to macroprolactin with normal concentrations of bioactive monomeric prolactin. Macroprolactinaemia has no pathological significance but, if it is not recognised as the cause, the apparent hyperprolactinaemia can lead to clinical confusion, unnecessary further investigations, inappropriate treatment and waste of healthcare resources. Macroprolactinaemia cannot be distinguished from true hyperprolactinaemia on clinical grounds alone but can be detected by a simple laboratory test based on the precipitation of macroprolactin with polyethylene glycol. Laboratory screening of all cases of hyperprolactinaemia to exclude macroprolactinaemia has been advised as best practice but has not been implemented universally and reports of clinical confusion caused by macroprolactinaemia continue to appear in the literature. Information provided by manufacturers to users of assays for prolactin regarding interference by macroprolactin is absent or inadequate and does not comply with the European Union Regulation covering in vitro diagnostic medical devices (IVDR). As the IVDR is implemented notified bodies should insist that manufacturers of assays for serum prolactin comply with the regulations by informing users that macroprolactin is a source of interference which may have untoward clinical consequences and by providing an estimate of the magnitude of the interference and a means of detecting macroprolactinaemia. Laboratories should institute a policy for excluding macroprolactinaemia in all cases of hyperprolactinaemia.


Corresponding author: Michael N. Fahie-Wilson, Clinical Biochemist, retired, Chiltern House, Bury St Edmunds, Suffolk, UK, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Michael Fahie-Wilson has served as consultant and provided advice to manufacturers of assays referred to in this work. All other authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

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Received: 2022-05-12
Accepted: 2022-06-01
Published Online: 2022-06-15
Published in Print: 2022-08-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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