Macroprolactin(s): composition and reactivity in immunoassays and laboratory interpretation of results of an unusual patient serum

Ann Clin Biochem 2006;43:57-62
doi:10.1258/000456306775141830
© 2006 Association for Clinical Biochemistry

 

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Original Articles


AR Ellis,
M Fahie-Wilson,
M Axcell,
K Sands and
RP Hill


UK NEQAS for Peptide Hormones, Department of Clinical Biochemistry, Royal Infirmary, Edinburgh EH16 4SA, UK;
Department of Biochemistry, Southend Hospital, Westcliff-on-Sea, Essex SSO ORY, UK;
Department of Biochemistry, Southend Hospital, Westcliff-on-Sea, Essex SSO ORY, UK;
Department of Medicine, Kings Mill Hospital, Sutton-in-Ashfield, Nottinghamshire NG17 4JL, UK;
Department of Clinical Chemistry, Kings Mill Hospital, Sutton-in-Ashfield, Nottinghamshire NG17 4JL, UK


Background: Macroprolactin is a high molecular mass complex of prolactin that may be the cause of elevated serum prolactin as determined by immunoassay. The composition of macroprolactin and its reactivity in immunoassays are variable but the complex has minimal bioactivity in vivo. Hyperprolactinaemia due tounrecognized macroprolactinaemia can lead to misdiagnosis andmistreatment.

Methods: Serum from a patient with an unusual pattern of immunoreactivitywas distributed to three users of each of the most popular immunoassaysrepresented in the UK National External Quality Assessment Scheme(NEQAS) for prolactin. Clinical details were provided and participatingcentres were invited to investigate the prolactin content ofthe specimen according to their local protocol, and to commenton their results. The nature of the macroprolactin in the specimenwas investigated in detail by gel filtration chromatographyof the native serum and of the serum after adsorption of IgGwith protein A, and by affinity chromatography with concanavalinA.

Results: Gel filtration studies revealed two peaks of macroprolactinin this serum. These macroprolactins were shown to be differentin their IgG content and degree of glycosylation. All eightimmunoassays reacted strongly with the macroprolactin present.The majority (78%) of centres that interpreted their resultseither demonstrated the presence of macroprolactin in the specimen,or suggested it as a likely cause of the hyperprolactinaemia.However, two centres inappropriately excluded macroprolactinaemiaas the cause of the elevated prolactin, and a further two didnot consider it at all. Data from previous UK NEQAS distributions(between 1996 and 2003) of macroprolactin containing sera arepresented which suggest that the frequency of recognition ofmacroprolactin as a possible cause of hyperprolactinaemia hasincreased over time.

Conclusions: Very high molecular mass forms of prolactin andthe presence of multiple molecular mass forms, as detected inthe case presented here, are uncommon. Also, the pattern ofimmunoreactivity reported in this specimen was unusual as mostmacroprolactins studied previously react less strongly in, forexample, the Bayer ADVIA Centaur assay compared to the RocheE170 assay. Both peaks of macroprolactin in this serum reactedin all assays tested. This case highlights the variable natureand immunoreactive behaviour of macroprolactin species.


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