Analysis of molecular heterogeneity of PRL is important in patients with hyperprolactinemia
Izabela Kokot 1 , Sylwia Płaczkowska 2 , Lilla Pawlik-Sobecka 1Abstract
Assessment of prolactin level in a medical laboratory is most frequently related to verifying the cause of the problems with fertility. However, hyperprolactinaemia diagnosis by laboratory test often does not reflect the clinical condition of a patient. Patients with hyperprolactinemia, but without characteristic symptoms related to this disorder, undergo further biochemical and/or image diagnosis, which could be harmful to the human organism. In some cases, pharmacological treatment and even surgical intervention are applied, although the cause of elevated prolactin levels has not been identified. Prolactin is present in blood in different forms and/or complexes. Most frequently, three basic isoforms of this hormone are distinguished: monomeric prolactin, big-prolactin, and big-big-prolactin, called a macroprolactin. The listed forms of prolactin have different biological activity, but in laboratory tests, all of them show immunoreactiveness. For that reason, prolactin is a large problem for laboratory diagnosticians and clinicians. The analysis of the presence of macroprolactin in blood samples with elevated prolactin level is not a routine matter, even though it has a key meaning in the further diagnostic process of hyperprolactinemia. A gold standard identifying all forms of prolactin is gel filtration chromatography, which gives qualitative and also quantitative results. Unfortunately, the equipment used for this method is not commonly available in medical laboratory. Results of many studies showed that the precipitation of macroprolactin with polyethylene glycol could be the screening method for evaluating the macroprolactinaemia prevalence. This procedure is simple and relatively low-cost, and though it has some analytical restrictions, its results correlate well with the results of the gel filtration chromatography. Macroprolactinaemia is present in a small percentage of the total population; however, it can occured in 53% patients with hyperprolactinaemia.
References
- 1. Bartoszewicz Z.: Makroprolaktynemia – hiperprolaktynemia charakteryzująca się obecnością wysokocząsteczkowej makroprolaktyny. Labforum, 2003; 14: 4-5
Google Scholar - 2. Beda K., Winczyk K.: Makroprolaktyna – występowanie, metody diagnostyczne i znaczenie kliniczne. Folia Med. Lodz, 2009; 36: 87-110
Google Scholar - 3. Beltran L., Fahie-Wilson M.N., McKenna T.J., Kavanagh L., Smith. T.P.: Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms. Clin. Chem., 2008; 54: 1673-1681
Google Scholar - 4. Bolanowski M.: Commentary on an Endocrine Society clinical practice guidelines published in Journal of Clinical Endocrinology and Metabolism 2011; 96: 273-288. Endokrynol. Pol., 2011; 62 (Suppl. 3): 23-24
Google Scholar - 5. Bukowska A., Pepłońska B.: Praca w nocy a prolaktyna jako czynnik ryzyka raka piersi. Med. Pracy, 2013; 64: 245-257
Google Scholar - 6. Casanueva F.F., Molitch M.E., Schlechte J.A., Abs R., Bonert V., Bronstein M.D., Brue T., Cappabianca P., Colao A., Fahlbusch R., Fideleff H., Hadani M., Kelly P., Kleinberg D., Laws E. i wsp.: Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin. Endocrinol., 2006; 65: 265-273
Google Scholar - 7. Chen Y., Wang H., Yang W., Jin W., Yu W., Wang W., Zhang K., Song G.: A new method of using polyethylene glycol (PEG) precipitation of macroprolactin to detect genuine hyperprolactinemia. J. Clin. Lab. Anal., 2016; 30: 1169-1174
Google Scholar - 8. Chen Y.J., Song G.Z., Wang Z.N.: A new criteria for screening macroprolactinemia using polyethylene glycol treatment combined with different assays for prolactin. Eur. Rev. Med. Pharmacol. Sci., 2016; 20: 1788-1794
Google Scholar - 9. Dolińska B., Łopata K., Ryszka F.: Prolaktyna i inne regulatory wchłaniania wapnia. Ann. Acad. Med. Siles., 2012; 66: 52-56
Google Scholar - 10. Fahie-Wilson M., Smith T.P.: Determination of prolactin: the macroprolactin problem. Best Pract. Res. Clin. Endocrinol. Metab., 2013; 27: 725-742
Google Scholar - 11. Hattori N.: Macroprolactinemia: a new cause of hyperprolactinemia. J. Pharmacol. Sci., 2003; 92: 171-177
Google Scholar - 12. Hattori N., Ikekubo K., Nakaya Y., Kitagawa K., Inagaki C.: Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies. J. Clin. Endocrinol. Metab., 2005; 90: 3036-3044
Google Scholar - 13. Hattori N., Nakayama Y., Kitagawa K., Ishihara T., Saiki Y., Inagaki C.: Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in macroprolactinemia. J. Endocrinol., 2006; 190: 287-293
Google Scholar - 14. Hattori N., Nakayama Y., Kitagawa K., Ishihara T., Saiki Y., Inagaki C.: Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia. Clin. Endocrinol., 2008; 68: 72-76
Google Scholar - 15. Hattori N., Nakayama Y., Kitagawa K., Li T., Inagaki C.: Development of anti-PRL (prolactin) autoantibodies by homologous PRL in rats: a model for macroprolactinemia. Endocrinology, 2007; 148: 2465-2470
Google Scholar - 16. Jackson R.D., Wortsman J., Malarkey W.B.: Macroprolactinemia presenting like a pituitary tumor. Am. J. Med., 1985; 78: 346-350
Google Scholar - 17. Jamaluddin F.A., Sthaneshwar P., Hussein Z., Othman N., Chan S.P.: Importance of screening for macroprolactin in all hyperprolactinaemic sera. Malays J. Pathol., 2013; 35: 59-63
Google Scholar - 18. Jarząbek-Bielecka G., Radomski D., Nowaczyk A., Sowińska-Przepiera E., Warchoł‑Biedermann K., Paluszkiewicz A.: Analiza stężeń prolaktyny u dziewcząt bez cech endokrynopatii z zaburzeniami miesiączkowania i stresem w wywiadzie. Gin. Prakt., 2010; 1: 46-53
Google Scholar - 19. Jeske W.: The main reasons behind variability in detection of prolactin and causes of true or apparent discordance with clinical state. Endokrynol. Pol., 2008; 59: 30-32
Google Scholar - 20. Jeske W., Zgliczyński W., Gorzelak K.: Macroprolactin in subjects with hyperprolactinaemia: clinical observations and relations between free PRL and PRL complexed with IgG. Endokrynol. Pol., 2005; 56: 779-784
Google Scholar - 21. Kałużny M., Bolanowski M.: Hyperprolactinemia: etiology, clinical symptoms, and therapy. Postępy Hig. Med. Dośw., 2005; 59: 20-27
Google Scholar - 22. Karasek M., Pawlikowski M., Lewiński A.: Hyperprolactinemia: causes, diagnosis, and treatment. Endokrynol. Pol., 2006; 57: 656-662
Google Scholar - 23. Kasum M., Oreskovic S., Zec I., Jezek D., Tomic V., Gall V., Adzic G.: Macroprolactinemia: new insights in hyperprolactinemia. Biochem. Med., 2012; 22: 171-179
Google Scholar - 24. Kavanagh L., McKenna T.J., Fahie-Wilson M.N., Gibney J., Smith T.P.: Specificity and clinical utility of methods for the detection of macroprolactin. Clin. Chem., 2006; 52: 1366-1372
Google Scholar - 25. Kokot I., Pawlik-Sobecka L., Płaczkowska S., Piwowar A.: Prolactin as an immunomodulatory factor in psoriatic arthritis. Postępy Hig. Med. Dośw., 2013; 67: 1265-1272
Google Scholar - 26. Konarzewska B., Szulc A., Popławska R., Galińska B., Juchnowicz D.: Wpływ poneuroleptycznej hiperprolaktynemii na występowanie zaburzeń seksualnych u mężczyzn chorych na schizofrenię. Psychiatr. Pol., 2008; 14: 87-95
Google Scholar - 27. Kostrzak A., Męczekalski B.: Makroprolaktynemia. Pol. Merk. Lek., 2010; 29: 47-49
Google Scholar - 28. Kostrzak A., Warenik-Szymankiewicz A., Męczekalski B.: Czy ocena aktywności biologicznej prolaktyny ma kluczowe znaczenie w diagnostyce hiperprolaktynemii? Pol. Merk. Lek., 2010; 28: 359-361
Google Scholar - 29. Lessing-Pernak J.: Znaczenie przebiegu porodu i wczesnego kontaktu matki z dzieckiem dla rozwoju przywiązania. Perinatol. Neonatol. Ginekol., 2010; 3: 282-289
Google Scholar - 30. McCudden C.R., Sharpless J.L., Grenache D.G.: Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin. Clin. Chim. Acta, 2010; 411: 155-160
Google Scholar - 31. Melmed S., Casanueva F.F., Hoffman A.R., Kleinberg D.L., Montori V.M., Schlechte J.A., Wass J.A., Endocrine Society: Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab., 2011; 96: 273-288
Google Scholar - 32. Michalik J., Bartoszewicz Z.: Prolactin (PRL) – multifunctional, hypophyseal peptide hormone. Postępy Biochem., 2002; 48: 296-305
Google Scholar - 33. Namiecińska M., Marciniak K., Nowak J.Z.: VEGF as an angiogenic, neurotrophic, and neuroprotective factor. Postępy Hig. Med. Dośw., 2005; 59: 573-583
Google Scholar - 34. Richa V., Rahul G., Sarika A.: Macroprolactin; a frequent cause of misdiagnosed hyperprolactinemia in clinical practice. J. Reprod. Infertil., 2010; 11: 161-167
Google Scholar - 35. Tkaczuk-Włach J., Sobstyl M., Chołubek-Robak D., Jakiel G.: Hiperprolaktynemia. Przegl. Menopauz., 2009; 2: 112-115
Google Scholar - 36. Whittaker P.G., Wilcox T., Lind T.: Maintained fertility in a patient with hyperprolactinemia due to big, big prolactin. J. Clin. Endocrinol. Metab., 1981; 53: 863-866
Google Scholar - 37. Wyszogrodzka-Kucharska A., Rabe-Jabłońska J.: Hyperprolactinemia in schizophrenic patients treated with antipsychotics. Post. Psychiatr. Neurol, 2004; 13: 355-362
Google Scholar - 38. Zaninotto M., Mion M.M., Altinier S., Varagnolo M., Venturini R., Plebani M.: Performance characteristics of laboratory testing and clinical outcomes. Clin. Chim. Acta, 2009; 404: 41-45
Google Scholar - 39. Zgliczyński W., Zdunowski P.: Hyperprolactinaemia – pitfalls in PRL assessment. Endokrynol. Pol., 2005; 56: 980-985
Google Scholar