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Macroprolactinemia: Predictability on clinical basis and detection by PEG precipitation with two different immunometric methods

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Abstract

Prolactin (PRL) in human serum is present in three species: monomeric PRL (23 kDA), big PRL (50–60 kDa) and big, big PRL (bb-PRL or macroprolactinemia) of 150–170 kDa. Macro-prolactin seems to be mainly composed of a molecule of monomeric PRL and an immunoglobulin G anti PRL. Its biological activity is considered low or absent, but it is measured, at various degrees, by the immunoassay method, thus causing diagnostic problems. Polyethylene Glycol (PEG) has been employed to precipitate macroprolactin, allowing its detection. This method is not applicable to all immunoassays for technical reasons. Our aim was to evaluate: 1) the predictability of macroprolactin on a clinical basis; 2) the possibility of applying PEG precipitation to Abbott AxSYM® analyzer beside Roche Elecsys® (already approved). We classified 34 hyperprolactinemic women, on a clinical and imaging basis, in four groups: A: functional hyperprolactinemia; B: pituitary lesions hyperprolactinemia; C: probably macroprolactinemia; D: unclassifiable hyperprolactinemia and a “control” group E of 19 healthy women. PRL was assayed, both with Elecsys® and AxSYM®, before and after PEG serum treatment. Eleven out of twelve group C, and 5/7 group D patients showed macroprolactinemia, against 1/7 in A and 1/8 in B. PEG was suitable for AxSYM® only after the same treatment of the calibration standards, thus performing outcomes overlapping Elecsys®. For clinical purposes, in the presence of macroprolactinemia, besides the recovery ratio, molar or ponderal monomeric PRL assay should be calculated.

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References

  1. Smith C.R., Norman M.R. Prolactin and growth hormone: molecular heterogeneity and measurement in serum. Ann. Clin. Biochem. 1990, 27: 542–550.

    Article  PubMed  CAS  Google Scholar 

  2. Lindstedt G. Endogenous antibodies against prolactin— a “new” cause of hyperprolactinemia. Eur. J. Endocrinol. 1994, 130: 429–432.

    Article  PubMed  CAS  Google Scholar 

  3. Cavaco B., Leite V., Santos M.A., Arranhado E., Sobrinho L.G. Some forms of big big prolactin behave as a complex of monomeric prolactin with an immunoglobulin G in patients with macroprolactinemia or prolactinoma. J. Clin. Endocrinol. Metab. 1995, 80: 2342–2346.

    PubMed  CAS  Google Scholar 

  4. Leite V., Cosby H., Sobrinho L.G., Fresnoza A., Amparo Santos M., Friesen H.G Characterization of big, big proactin in patients with hyperprolactinaemia. Clin. Endocrinol. (Oxf). 1992, 37: 365–372.

    Article  PubMed  CAS  Google Scholar 

  5. Hattori N. The frequency of macroprolactinemia in pregnant women and the heterogeneity of its etiologies. J. Clin. Endocrinol. Metab. 1996, 81: 586–590.

    PubMed  CAS  Google Scholar 

  6. Pascoe-Lira D., Duran-Reyes G., Contreras-Hernandez I., Manuel-Apolinar L., Blanco-Favela F., Leanos-Miranda A. Frequency of macroprolactinemia due to autoantibodies against prolactin in pregnant women. J. Clin. Endocrinol. Metab. 2001, 86: 924–929.

    Article  PubMed  CAS  Google Scholar 

  7. Hattori N., Ikekubo K., Ishihara T., Moridera K., Hino M., Kurahachi H. Correlation of the antibody titers with serum prolactin levels and their clinical course in patients with anti-prolactin autoantibody. Eur. J. Endocrinol. 1994, 130: 438–45.

    Article  PubMed  CAS  Google Scholar 

  8. Corenblum B. Asymptomatic hyperprolactinemia resulting from macroprolactinemia. Fertil. Steril. 1990, 53: 165–167.

    PubMed  CAS  Google Scholar 

  9. Fideleff H.L., Ruibal G., Boquete H., Pujol A., Sequera A., Sobrado P. Macroprolactinemia in childhood and adolescence: a cause of asymptomatic hyperprolactinemia. Horm. Res. 2000, 53: 16–19.

    Article  PubMed  CAS  Google Scholar 

  10. Blanco-Favela F., Chavez-Rueda K.A., Leanos-Miranda A. Analysis of anti-prolactin autoantibodies in systemic lupus erythematosus. Lupus 2001, 10: 757–761.

    Article  PubMed  CAS  Google Scholar 

  11. Leanos-Miranda A., Chavez-Rueda K.A., Blanco-Favela F. Biologic activity and plasma clearance of prolactin-IgG complex in patients with systemic lupus erythematosus. Arthritis. Rheum. 2001, 44: 866–875.

    Article  PubMed  CAS  Google Scholar 

  12. Andersen A.N., Pedersen H., Djursing H., Andersen B.N., Friesen H.G. Bioactivity of prolactin in a woman with an excess of large molecular size prolactin, persistent hyperprolactinemia and spontaneous conception. Fertil. Steril. 1982, 38: 625–6288 (VRF).

    PubMed  CAS  Google Scholar 

  13. Vieira J.G., Tachibana T. T., Obara L. H. Extensive experience and validation of polyethylene glycol precipitation as a screening method for macroprolactinemia. Clin. Chem. 1998, 44: 1758–1759.

    PubMed  CAS  Google Scholar 

  14. Fahie-Wilson M.N., Soule S.G. Macroprolactinaemia: contribution to hyperprolactinaemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann. Clin. Biochem. 1997, 34: 252–258.

    Article  PubMed  CAS  Google Scholar 

  15. Fahie-Wilson M., Brunsden P., Surrey J., Everitt A. Macroprolactin and the Roche Elecsys prolactin assay: characteristics of the reaction and detection by precipitation with polyethylene glycol. Clin. Chem. 2000 46: 1993–1995.

    PubMed  CAS  Google Scholar 

  16. Sanchez-Eixeres M.R., Mauri M., Alfayate R. et al. Prevalence of macroprolactin detected by Elecsys 2010. Horm. Res. 2001, 56: 87–92.

    Article  PubMed  CAS  Google Scholar 

  17. Sapin R., Gasser F., Grucker D. Free prolactin determinations in hyperprolactinemic men with suspicion of macroprolactinemia. Clin. Chim. Acta 2002, 316: 33–41.

    Article  PubMed  CAS  Google Scholar 

  18. Hattori N., Ikekubo K., Ishihra T., Moridera K., Hino M., Kurahachi H. Effects of anti-prolactin autoantibodies on serum prolactin measurements. Eur. J. Endocrinol. 1994, 130: 434–437.

    Article  PubMed  CAS  Google Scholar 

  19. Malarkey W. B., Jackson R., Wortsman J. Long-term assessment of patients with macroprolactinemia. Fertil. Steril. 1988, 50: 413–418.

    PubMed  CAS  Google Scholar 

  20. Olukoga A.O., Kane J.W. Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition. Clin. Endocrinol. (Oxf). 1999, 51: 119–126.

    Article  PubMed  CAS  Google Scholar 

  21. Vallette-Kasic S., Morange-Ramos I., Selim A. et al. Macroprolactinemia revisited: a study on 106 patients. J. Clin. Endocrinol. Metab. 2002 87: 581–588.

    Article  PubMed  CAS  Google Scholar 

  22. Cavaco B., Prazeres S., Santos M.A. Sobrinho L.G., Leite V. Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays. J. Endocrinol. Invest. 1999, 22: 203–208.

    Article  PubMed  CAS  Google Scholar 

  23. Schneider W., Marcovitz S., Al-Shammari S., Yago S., Chevalier S. Reactivity of macroprolactin in common automated immunoassays. Clin. Biochem. 2001, 34: 469–473.

    Article  PubMed  CAS  Google Scholar 

  24. Leslie H., Courtney C.H., Bell P.M. et al. Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method. J. Clin. Endocrinol. Metab. 2001, 86: 2743–2746.

    Article  PubMed  CAS  Google Scholar 

  25. Gilson G., Schmit P., Thix J., Hoffman J.P., Humbel R.L. Prolactin results for samples containing macroprolactin are method and sample dependent. Clin. Chem. 2001, 47: 331–333.

    PubMed  CAS  Google Scholar 

  26. Larrea F., Escorza A., Valero A. Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal function. J. Clin. Endocrinol. Metab. 1989, 68: 982–987.

    Article  PubMed  CAS  Google Scholar 

  27. Jackson R.D., Wortsman J., Malarkey W.B. Persistence of arge molecular weight prolactin secretion during pregnancy in women with macroprolactinemia and its presence in fetal cord blood. J Clin Endocrinol Metab. 1989, 68: 1046–1050.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Pierluigi Amadori.

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Amadori, P., Dilberis, C., Marcolla, A. et al. Macroprolactinemia: Predictability on clinical basis and detection by PEG precipitation with two different immunometric methods. J Endocrinol Invest 26, 148–156 (2003). https://doi.org/10.1007/BF03345144

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