Preferences help
enabled [disable] Abstract
Number of results
2009 | 36 | 2 | 87-110
Article title

Makroprolaktyna - występowanie, metody diagnostyczne i znaczenie kliniczne

Title variants
Macroprolactin - prevalence, diagnostic methods and clinical significance
Languages of publication
Macroprolactin (MaPRL) is a high molecular mass variant of prolactin (PRL), which usually consists of a monomeric PRL and an immunoglobulin G molecule. This form does not show any significant biological activity, however it retains immunoreactivity. Therefore, MaPRL induces increase in hormone concentration in laboratory tests, which results in many diagnostic and therapeutic mistakes. Most of immunoassays do not distinguish between monomeric PRL and MaPRL, therefore performing additional tests that could detect macroprolactin is suggested. This review presents different methods of MaPRL detection and their usefulness in standard laboratory practice. Moreover, data from the literature concerning the role of macroprolactinaemia in clinical practice are discussed.
Makroprolaktyna (MaPRL) jest wielkocząsteczkową formą prolaktyny (PRL) zbudowaną zazwyczaj z monomerycznej PRL i cząsteczki immunoglobuliny G. Nie posiada istotnej aktywności biologicznej, ale z powodu zachowanej immunoreaktywności powoduje wzrost stężenia hormonu we krwi i u osób z hiperprolaktynemią jest przyczyną wielu pomyłek diagnostycznoterapeutycznych. Większość zestawów do oznaczeń PRL nie rozróżnia monomerycznej od wielkocząsteczkowej postaci hormonu, więc wskazane jest wykonywanie dodatkowych testów wykrywających MaPRL. W pracy omówiono różne techniki identyfikacji MaPRL i ich przydatność w codziennej diagnostyce laboratoryjnej, a także przedstawiono dane literaturowe dotyczące znaczenia makroprolaktynemii w praktyce klinicznej.

Physical description
  • Zakład Neuroendokrynologii, Uniwersytet Medyczny w Łodzi
  • Zakład Neuroendokrynologii, Uniwersytet Medyczny w Łodzi
  • Suliman AM, Smith TP, Gibney J, McKenna TJ. Frequent misdiagnosis and mismanagement of hyperprolactinemic patients before the introduction of macroprolactin screening: application of a new strict laboratory definition of macroprolactinemia. Clin Chem. 2003; 49: 1504-1509.
  • Zgliczyński W, Zdunowski P. Hiperprolactinaemia – pitfalls in PRL assessment. Pol J Endocrinol. 2005; 6: 980-985.
  • Jeske W. Przyczyny rozbieżności wynikow oznaczeń prolaktyny i powody prawdziwej albo pozornej niezgodności ze stanem klinicznym. Endokrynol Pol. 2008; 59: 30-32.
  • Freeman M, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function and regulation of secretion. Physiol Rev. 2000; 80: 1523-1631.
  • Karasek M, Pawlikowski M, Lewiński A. Hyperprolactinemia: causes, diagnosis, and treatment. Pol J Endocrinol. 2006; 6: 656-662.
  • Sadideen H, Swaminathan R. Macroprolactin: what is it and what is its importance? Int J Clin Pract. 2006; 60: 457-461.
  • Hattori N. Macroprolactinemia: a New Cause of Hyperprolactinemia. J Pharmacol Sci. 2003; 92: 171-177.
  • Suh HK, Frantz AG. Size heterogeneity of human prolactin in plasma and pituitary extracts. J Clin Endocrinol Metab. 1974; 39: 928-935.
  • Whittaker PG, Wilcox T, Lind T. Maintained fertility in a patient with hyperprolactinemia due to big, big prolactin. J Clin Endocrinol Metab. 1981; 53: 863-866.
  • Jackson RD, Wortsman J, Malarkey WB. Macroprolactinemia presenting like a pituitary tumor. Am J Med. 1985; 78: 346-350.
  • Leite V, Cosby H, Sobrihno LG i wsp.Characterization of big, big prolactin in patients with hyperprolactinaemia. Clin Endocrinol. 1992; 37: 365-372.
  • Hattori N, Ishihara T, Ikekubo K i wsp. Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia. J Clin Endocrinol Metab. 1992; 75: 1226-1229.
  • Hattori N, Ikekubo K, Isihara T i wsp. A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion. Acta Endocrinol (Copenh). 1992; 12: 497-500.
  • Cavaco B, Leite V, Amparo Santos M i wsp. Some forms of big big prolactin behave as a complex of monomeric prolactin with an immunoglobulin G in patients with macroprolactinemia or prolactinoma. Clin Endocrinol Metab. 1995; 80: 2342-2346.
  • 15. Hattori N, Inagaki C. Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab. 1997; 82: 3107-3110.
  • Bartoszewicz Z. Makroprolaktynemia – hiperprolaktynemia charakteryzująca się obecnością wysokocząsteczkowej makroprolaktyny. LabForum
  • Mel'nichenko GA, Goncharov NP, Dzeranova LK, Barmina II. Clinical and laboratory aspects of the phenomenon of macroprolactinemia. Vestn Ross Akad Med Nauk. 2007; 3: 52-54.
  • Bernadotte F, Mattsson R. A fraction of murine placental extract enhances IgA production in cultured splenocytes. J Reprod Immunol. 1992; 21: 189-202.
  • Schiettecatte J, Van Opdenbosch A, Anckaert E i wsp. Immunoprecipitation for rapid detection of macroprolactin in the form of prolactin-immunoglobulin complexes. Clin Chem. 2005; 51: 1746-1748.
  • Carlson HE, Markoff E, Lee DW. On the nature of serum prolactin in two patients with macroprolactineia. Fertil Steril. 1992; 58: 78-87.
  • Ahlquist JA, Fahie-Wilson MN. On the origin and distribution of macroprolactin. J Endocrinol. 2000; 164: P34.
  • Hattori N, Ikekubo K, Nakaya Y i wsp. Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies. J Clin Endocrinol Metab. 2005; 90: 3036–3044.
  • Hattori N, Nakayama Y, Kitagawa K i wsp. Development of anti-PRL (prolactin) autoantibodies by homologous PRL in rats: A model for macroprolactinemia. Endocrinology 2007; 148: 2465–2470.
  • Smith CR, Norman MR. Prolactin and growth hormone: molecular heterogeneity and measurement in serum. Ann Clin Biochem. 1990; 27: 542-550.
  • Olukoga AO, Kane JW. Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition. Clin Endocrinol (Oxf). 1999; 51: 119-126.
  • Leslie H, Courtney CH, Bell PM i wsp. 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.
  • Hattori N. The frequency of macroprolactinemia in pregnant women and the heterogeneity of its etiologies. J Clin Endocrinol Metab. 1996; 81: 586-590.
  • Fahie-Wilson MN, Soule SG. 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.
  • Jeske W, Zdunowski P, Bartoszewicz Z i wsp. Large molecular weight prolactin in patients with hyperprolactinaemia. Endokrynol Pol. 2000; 51: 237-248.
  • Sanchez-Eixeres MR, Mauri M, Alfayate R i wsp. Prevalence of macroprolactin detected by ElecsysR 2010. Horm Res. 2001; 56: 87-92.
  • Hauache OM, Rocha AJ, Maia Jr ACM i wsp. Screening for macroprolactinaemia and pituitary imaging studies. Clin Endocrinol. 2002; 57: 327-331.
  • Sapin R, Gasser F, Grucker D. Free prolactin determinations in hyperprolactinemic men with suspicion of macroprolactinemia. Clin Chim Acta 2002;316: 33-41.
  • Vallette-Kasic S, Morange-Ramos I, Selim A i wsp. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab. 2002; 87: 581-588.
  • Smith TP, Suliman AM, Fahie-Wilson MN, McKenna TJ. Gross-variability in the detection of prolactin in sera containing big big prolactin (macroprolactin) by commercial immunoassays. J Clin Endocrinol Metab. 2002; 87: 5410–5415.
  • Ellis MJ, Livesey JH, Soule SG. Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay. Clin Biochem. 2006; 39: 1028–1034.
  • Hattori N, Nakayama Y, Kitagawa K i wsp. Anti-prolactin (PRL) autoantibodybinding sites (epitopes) on PRL molecule in macroprolactinemia. J Endocrinol. 2006; 190: 287–293.
  • Alfonso A, Rieniets KI, Vigersky RA. Incidence and clinical significance of elevated macroprolactin levels in patients with hyperprolactinemia. Endocr Pract. 2006; 12: 275-280.
  • Vilar L, Moura E, Canadas V i wsp. Prevalence of macroprolactinemia among 115 patients with hyperprolactinemia. Arq Bras Endocrinol Metabol. 2007; 51: 86-91.
  • Vilar L, Freitas MC, Naves LA i wsp. Diagnosis and management of hyperprolactinemia: results of a Brazilian multicenter study with 1234 patients. J Endocrinol Invest. 2008; 31: 436-444.
  • Hattori N, Ishihara T, Saiki Y. Macroprolactinaemia: prevalence and aetiologies in a large group of hospital workers. Clin Endocrinol. 2009; 71: 702–708.
  • Don-Wauchope AC, Hoffmann M, le Riche M, Ascott-Evans BH. review of the prevalence of macroprolactinaemia in a South African hospital. Clin Chem Lab Med. 2009; 47: 882-884.
  • Jassam NF, Paterson A, Lippiatt C, Barth JH. Macroprolactin on the Advia Centaur: experience with 409 patients over a three-year period. Ann Clin Biochem. 2009; 46: 501-504.
  • McCudden CR, Sharpless JL, Grenache DG. Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin. Clin Chim Acta. 2010; 411: 155–160.
  • Farkouh NH, Packer MG, Frantz A. Large molecular size prolactin with reduced receptor activity in human serum: high proportion in basal state and reduction after thyrotropin-releasing hormone. J Clin Endo Metab. 1979; 48: 1026-1032.
  • Andersen AN, Pedersen H, Djursing H i wsp. Bioactivity of prolactin in a woman with an excess of large molecular size prolactin, persistent hyperprolactinemia and spontaneous conception. Fertil Steril. 1982; 38: 625-628.
  • Hattori N, Nakayama Y, Kitagawa K i wsp. Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia. Clin Endocrinol. 2008; 68: 72–76.
  • Olukoga AO. Macroprolactin is clinically important (Letter). J Clin Endocrinol Metab. 2002; 87: 4833-4834.
  • Cavaco B, Prazeres S, Santos MA i wsp. Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays. J Endocrinol Invest. 1999; 22: 203-208.
  • Schneider W, Marcovitz S, Al-Shammari S i wsp. Reactivity of macroprolactin in common automated immunoassays. Clin Biochem. 2001; 34: 469–473.
  • Fahie-Wilson MN, McKenna TJ , Ahlquist JA, Smith TP. Macroprolactin and the Pituitary Society guidelines for the diagnosis and management of prolactinomas. Clin Endocrinol. 2007; 67: 637–641.
  • Seth J, Sturgeon CM, Ellis AR i wsp. UK NEQAS for peptide hormones and related substances. Annual Rev. 1998. Edinburgh: Dept. of Clinical Biochemistry 1998: A1–A4.
  • Beltran L, Fahie-Wilson MN, McKenna TJ i wsp. 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.
  • Prazeres S, Amparo Santos M, Ferreira HG, Sobrinho LG. A practical method for the detection of macroprolactinaemia using ultrafiltration. Clin Endocrinol. 2003; 58: 686–690.
  • Fahie-Wilson MN, Ahlquist JA. Hyperprolactinaemia due to macroprolactins: some progress but still a problem. Clin Endocrinol. 2003; 58: 683–685.
  • Jeske W, Zgliczyński W, Gorzelak K. Makroprolaktyna u osob z hiperprolaktynemią: Obserwacje kliniczne i relacje pomiędzy frakcją prolaktyny wolnej i frakcją prolaktyny związanej z IgG. Endokrynol Pol. 2005; 5: 779-784.
  • Vieira J, Tachibana T, Obara L, Maciel R. Extensive experience and validation of polyethylene glycol precipitation as a screening method for macroprolactinemia. Clin Chem. 1998; 44: 1758-1759.
  • Rivero A, Alonso E, Grijalba A. Decision cut-off of the polyethylene glycol precipitation technique in screening for macroprolactinemia on Immulite 2000. Clin Chem Lab Med. 2004; 42: 566–568.
  • Gibney J, Smith TP, McKenna TJ. The impact on clinical practice of routine screening for macroprolactin. J Clin Endocrinol Metab. 2005 90: 3927–3932.
  • Kavanagh L, McKenna TJ, Fahie-Wilson MN i wsp. Specificity and clinical utility of methods for the detection of macroprolactin. Clin Chem. 2006; 52: 1366–1372.
  • Kavanagh-Wright L, Smith TP, Gibney J, McKenna TJ. Characterization of macroprolactin and assessment of markers of autoimmunity in macroprolactinaemic patients. Clin Endocrinol. 2009; 70: 599–605.
  • Ram S, Harris B, Fernando JJ i wsp. False-positive polyethylene glycol precipitation tests for macroprolactin due to increased serum globulins. Ann Clin Biochem. 2008; 45: 256-259.
  • Schiettecatte J, De Schepper J, Velkeniers B i wsp. Rapid detection of macroprolactin in the form of prolactin-immunoglobulin G complexes by immunoprecipitation with anti-human IgG-agarose. Clin Chem Lab Med. 2001; 39:1244-1248.
  • Craddock HS, Fahie-Wilson M, Heys AD. Macroprolactin detection by ultrafiltration screening with the Abbott AxSYM assay. In Proceedings of Pathology 2000. Association of Clinical Biochemists National Meeting, p. 148. The Association of Clinical Biochemists, London, U.K.
  • Quinn AM, Rubinas TC, Garbincius JC, Holmes EW. Determination of ultrafilterable prolactin elimination of macroprolactin interference with a monomeric prolactin-selective sample pretreatment. Arch Pathol Lab Med. 2006; 130: 1807–1812
  • Landberg E, Wahlberg J, Ryden I i wsp. Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration. Clin Chim Acta. 2007; 376: 220–225.
  • Bjorck L, Kronvall G. Purification and some properties of streptococcal protein g, a novel IgG-binding reagent. J Immunol. 1984; 133: 969-974.
  • McKenna J, Smith T. Hyperprolactinemia due to macroprolactin a commonly unrecognized phenomenon causing misdiagnosis and mismanagement. The Endocrinologist 2008;18:249–254.
  • Cattaneo FA, Fahie-Wilson MN. Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report. J Neurosurg. 2001; 95: 334-337.
  • Bjoro T, Morkrid L, Wergeland R i wsp. Frequency of hyperprolactinaemia due to large molecular weight prolactin (150-170 kD PRL). Scand J Clin Lab Invest. 1995; 55: 139-147.
  • Miyai K, Ichihara K, Kondo K, Mori S. Asymptomatic hyperprolactinaemia and prolactinoma in the general population-mass screening by paired assays of serum prolactin. Clin Endocrinol (Oxf). 1986 ; 25: 549-554.
  • Guay AT, Sabharwal P, Varma S, MalarkeyWB. Delayed diagnosis of psychological erectile dysfunction because of the presence of macroprolactinaemia. J Clin Endocrinol Metab. 1996; 81: 2512–2514.
  • Weill J, Petit S, Stuckens C i wsp. Macroprolactinemia in a child. Arch Fr Pediatr 1990; 47: 595-596.
  • Schlechte JA. The macroprolactin problem. J Clin Endocrinol Metab. 2002; 87: 5408-5409.
  • Casanueva FF, Molitch ME, Schlechte JA i wsp. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol. 2006; 65: 265–273.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.