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Endocrinology and Metabolism |
1 Departments of Investigative Endocrinology and
2
Medicine, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland.
3 The Conway Institute of Biomolecular and Biomedical Research, University College, Belfield, Dublin 4, Ireland.
aAuthor for correspondence. Fax 00-353-1-209-4981; e-mail tmckenna{at}svherc.ucd.ie.
Background: Macroprolactin (big big prolactin) has reduced bioactivity and is measured by immunoassays for prolactin when it accumulates in the plasma of some individuals. We applied normative data for serum prolactin after treatment of sera to remove macroprolactin to elucidate the contribution of macroprolactin to misleading diagnoses, inappropriate investigations, and unnecessary treatment.
Methods: We reviewed records of women attending a tertiary referral center who had prolactin >1000 mIU/L. Application of a reference interval to polyethylene glycol (PEG)-treated hyperprolactinemic sera identified 21 patients in whom hyperprolactinemia was accounted for entirely by the presence of macroprolactin. Presenting clinical features, diagnoses, and treatment were compared in these patients and 42 age-matched true hyperprolactinemic patients.
Results: Prolactin concentrations in sera of 110 healthy individuals ranged from 78 to 564 mIU/L. The range of values for the sera after PEG treatment was 70–403 mIU/L. For macroprolactinemic samples, PEG treatment decreased mean (SD) prolactin from 1524 (202) mIU/L to 202 (27) mIU/L but decreased it only from 2096 (233) mIU/L to 1705 (190) mIU/L in true hyperprolactinemic patients (P <0.01 between groups). Oligomenorrhea or amenorrhea and galactorrhea were the most common clinical features in both groups, although they occurred more frequently in true hyperprolactinemic patients (P <0.05). Serum estradiol and luteinizing hormone concentrations were significantly higher in participants with macroprolactinemia than in those with true hyperprolactinemia (P <0.05). Among participants with retrospectively identified macroprolactinemia, pituitary imaging was performed in 93% and treatment with dopamine agonist was prescribed in 87%.
Conclusions: Macroprolactin is a significant cause of misdiagnosis, unnecessary investigation, and inappropriate treatment. The use of an appropriate reference interval for the PEG immunoprecipitation procedure may be of particular importance in those patients who have an excess of both macroprolactin and monomeric prolactin.
The following articles in journals at HighWire Press have cited this article:
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  M. Fahie-Wilson and D. Halsall Polyethylene glycol precipitation: proceed with care Ann Clin Biochem, May 1, 2008; 45(3): 233 - 235. [Full Text] [PDF]
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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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 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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 T. C. Friedman, W. T. Couldwell, M. H. Weiss, E. R. Laws Jr., G. L. Hortin, A. Colao, G. Lombardi, and J. Schlechte Prolactinomas N. Engl. J. Med., March 4, 2004; 350(10): 1054 - 1057. [Full Text] [PDF]
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M. Fahie-Wilson In Hyperprolactinemia, Testing for Macroprolactin Is Essential Clin. Chem., September 1, 2003; 49(9): 1434 - 1436. [Full Text] [PDF]
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