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Interference by macroprolactin in assays for prolactin: will the In Vitro Diagnostics Regulation lead to a solution
Michael N Fahie-Wilson1, Christa M Cobbaert2, Andrea R Horvath3
1Clinical Biochemist, retired, Chiltern House, Bury St Edmunds, Suffolk, UK.
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.
Insights
Macroprolactinaemia, a common interference in serum prolactin tests, causes falsely elevated results. This condition, often missed, leads to misdiagnosis and unnecessary treatments, highlighting the need for routine laboratory screening.
Area of Science:
- Clinical Chemistry
- Endocrinology
- In Vitro Diagnostics
Background:
- Assays for serum prolactin are frequently affected by interference from macroprolactin, a high molecular weight complex.
- This interference leads to falsely elevated prolactin levels (macroprolactinaemia) in 5-25% of cases, mimicking true hyperprolactinaemia.
- Macroprolactinaemia itself has no pathological significance but can cause significant clinical confusion and resource waste if unrecognized.
Purpose of the Study:
- To highlight the clinical and diagnostic challenges posed by macroprolactinaemia.
- To emphasize the inadequacy of current prolactin assay information regarding macroprolactin interference.
- To advocate for improved laboratory practices and regulatory compliance for in vitro diagnostic devices.
Main Methods:
- Discussion of the clinical presentation and laboratory detection of macroprolactinaemia.
- Review of existing prolactin assay interference issues and manufacturer information.
- Analysis of the implications of macroprolactinaemia in the context of diagnostic regulations (IVDR).
Main Results:
- Macroprolactinaemia is a prevalent cause of falsely diagnosed hyperprolactinaemia, leading to unnecessary investigations and treatments.
- Current prolactin assay manufacturers often provide inadequate information on macroprolactin interference, failing to meet regulatory standards.
- A simple polyethylene glycol precipitation test can effectively detect macroprolactinaemia.
Conclusions:
- Laboratories should implement routine screening for macroprolactinaemia in all cases of apparent hyperprolactinaemia.
- Manufacturers of prolactin assays must comply with the IVDR by clearly informing users about macroprolactin interference and detection methods.
- Standardized detection and reporting of macroprolactinaemia are crucial to prevent clinical confusion and optimize healthcare resource allocation.
