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Letters |
Department of Clinical Chemistry, Southend Hospital, Prittlewell Chase, Westcliff-on-Sea, Essex SS0 0RY, United Kingdom, Fax 44-01702-221059
To the Editor:
Vieira et al. (1) used the Wallac Delfia
immunofluorometric assay to demonstrate that macroprolactin is a common
cause of apparent hyperprolactinemia, and this confirms our
experience (2) and that of others (3). However,
their data validating the polyethylene glycol (PEG) precipitation as a
screening method for detecting macroprolactinemia are substantially
different than ours (2) and appear to be inconsistent. They
suggest that a recovery of >65% of serum prolactin (PRL) after PEG
precipitation indicates the absence of macroprolactin; however, their
Fig. 1
shows that samples giving such recoveries contained 10–40%
high-molecular weight PRL as determined by gel filtration
chromatography. Furthermore, the data shown in Fig. 1
of the recovery
of PRL after PEG precipitation and the proportion of PRL present as the
high-molecular weight forms determined by gel filtration show
considerable scatter such that a sample showing 50% recovery after
precipitation with PEG might contain 15–95% macroprolactin. Their
reproducibility studies also showed considerable imprecision (CV,
7–28%) for the PEG precipitation technique, and this may be one
contributing factor.
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In my experience, the PEG precipitation test has been more reproducible (CVs, 5.8% and 6.5%) and more definitive. An initial report (2) demonstrated that in 69 cases with PRL >19.4 µg/L (700 milliunits/L), the recovery of >40% of the PRL after precipitation with PEG identified all 52 samples containing only monomeric PRL but included one sample containing 10% of the immunoreactive PRL as macroprolactin. A recovery of <40% identified all 16 samples containing substantial quantities of macroprolactin (34–90% of the immunoreactive PRL).
I have now used precipitation with PEG to examine 195 samples with
total PRL >19.4 µg/L (700 milliunits/L) over a 38-month period.
Using a conservative cutoff of 50%,I found low recovery after PEG
precipitation in 30 samples (15.4%); the presence of macroprolactin
was confirmed by gel filtration chromatography in all but one sample.
Similar results were obtained in a neighboring district, with
macroprolactin identified in 25 of 145 (17.2%) samples. These data are
summarized in Fig. 1
and demonstrate that when macroprolactin is present it is the
predominant immunoreactive form of PRL present. When no macroprolactin
is present, gel filtration chromatography shows no peak of higher
molecular weight PRL.
The reasons for the differences between my experience with PEG precipitation and that of Vieira et al. (1) are not immediately apparent. I have used a similar technique with identical reagent concentrations but use reagents at room temperature, whereas Vieira keep their PEG at 4 °C. Temperature affects the recovery of PRL after precipitation with PEG (2), and this may be a source of variation. However, most of the differences may be related to their definition of the presence or absence of macroprolactin on gel filtration chromatography. It is not clear whether a clearly defined peak of macroprolactin was demonstrated in all samples categorized as containing high-molecular weight forms of PRL, and it would be most helpful if representative chromatograms were published so that the efficiency of the separation can be seen.
In my experience, macroprolactin is a common cause of apparent hyperprolactinemia and a cause of diagnostic confusion, which may lead to inappropriate treatment. I agree with Vieira et al. (1) and Lindstedt (4) that all samples showing apparent hyperprolactinemia should be examined for macroprolactin; however, it should be noted that although all commercial assays for PRL investigated thus far react with macroprolactin (albeit to a varying extent), not all of these assays can be used with the PEG precipitation technique (2). Centrifugal ultrafiltration may provide an alternative means of demonstrating the presence of macroprolactin (5), and additional work is in progress to validate this technique.
References
The following articles in journals at HighWire Press have cited this article:
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  S. Ram, B. Harris, J. J R Fernando, R. Gama, and M. Fahie-Wilson False-positive polyethylene glycol precipitation tests for macroprolactin due to increased serum globulins Ann Clin Biochem, May 1, 2008; 45(3): 256 - 259. [Abstract] [Full Text] [PDF]
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 L. Kavanagh, T. J. McKenna, M. N. Fahie-Wilson, J. Gibney, and T. P. Smith Specificity and Clinical Utility of Methods for the Detection of Macroprolactin Clin. Chem., July 1, 2006; 52(7): 1366 - 1372. [Abstract] [Full Text] [PDF]
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J. Schiettecatte, A. Van Opdenbosch, E. Anckaert, J. De Schepper, K. Poppe, B. Velkeniers, and J. Smitz Immunoprecipitation for Rapid Detection of Macroprolactin in the Form of Prolactin-Immunoglobulin Complexes Clin. Chem., September 1, 2005; 51(9): 1746 - 1748. [Full Text] [PDF]
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 J. Gibney, T. P. Smith, and T. J. McKenna The Impact on Clinical Practice of Routine Screening for Macroprolactin J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3927 - 3932. [Abstract] [Full Text] [PDF]
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M. J. Ellis and J. H. Livesey Techniques for Identifying Heterophile Antibody Interference Are Assay Specific: Study of Seven Analytes on Two Automated Immunoassay Analyzers Clin. Chem., March 1, 2005; 51(3): 639 - 641. [Full Text] [PDF]
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 S. Ram, D. Blumberg, P. Newton, N. R. Anderson, and R. Gama Raised serum prolactin in rheumatoid arthritis: genuine or laboratory artefact? Rheumatology, October 1, 2004; 43(10): 1272 - 1274. [Abstract] [Full Text] [PDF]
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A. M. Suliman, T. P. Smith, J. Gibney, and T. J. McKenna Frequent Misdiagnosis and Mismanagement of Hyperprolactinemic Patients before the Introduction of Macroprolactin Screening: Application of a New Strict Laboratory Definition of Macroprolactinemia Clin. Chem., September 1, 2003; 49(9): 1504 - 1509. [Abstract] [Full Text] [PDF]
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 C. Mounier, J. Trouillas, B. Claustrat, R. Duthel, and B. Estour Macroprolactinaemia associated with prolactin adenoma Hum. Reprod., April 1, 2003; 18(4): 853 - 857. [Abstract] [Full Text] [PDF]
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S. Vallette-Kasic, I. Morange-Ramos, A. Selim, G. Gunz, S. Morange, A. Enjalbert, P.-M. Martin, P. Jaquet, and T. Brue Macroprolactinemia Revisited: A Study on 106 Patients J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 581 - 588. [Abstract] [Full Text] [PDF]
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H. Leslie, C. H. Courtney, P. M. Bell, D. R. Hadden, D. R. McCance, P. K. Ellis, B. Sheridan, and A. B. Atkinson Laboratory and Clinical Experience in 55 Patients with Macroprolactinemia Identified by a Simple Polyethylene Glycol Precipitation Method J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2743 - 2746. [Abstract] [Full Text] [PDF]
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M. Fahie-Wilson, P. Brunsden, J. Surrey, and A. Everitt Macroprolactin and the Roche Elecsys Prolactin Assay: Characteristics of the Reaction and Detection by Precipitation with Polyethylene Glycol Clin. Chem., December 1, 2000; 46(12): 1993 - 1995. [Full Text] [PDF]
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M. N. Fahie-Wilson and R. John Detection of Macroprolactin Causing Hyperprolactinemia in Commercial Assays for Prolactin Dr. John responds: Clin. Chem., December 1, 2000; 46(12): 2022 - 2023. [Full Text] [PDF]
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