Abstract
Macroprolactinemia, i.e. sustained hyperprolactinemia where the predominant circulating form of prolactin (PRL) is of large molecular weight, is a common phenomenon comprising up to one-fourth of all cases of hyperprolactinemia. We measured serum PRL levels by four different immunoassay systems (PROL-CTK, RIAgnost, Delfia, ACS 180) and by the Nb2 bioassay in patients with prolactinomas/idiopathic hyperprolactinemias in whom monomeric PRL was the major species of PRL (n=11, group 1) and in patients with macroprolactinemia (n=12, group 2). In group 1, the results obtained with the different immunoassays and with the Nb2 assay were highly correlated (r=0.945−0.982). On the other hand, big big-PRL (bb-PRL) was differently recognized by the immunoassays, since measured serum PRL values from each patient were highly variable in group 2. RIA-gnost Prolactin and Delfia Prolactin detected bb-PRL similarly and they were highly correlated with each other (r=0.937, p<0.0001). ACS 180 detected bb-PRL somewhat differently from the RIA-gnost and Delfia systems, but likewise most of the patients of group 2 had PRL values above normal. PROL-CTK was the method less influenced by the presence of bb-PRL since most of the subjects with macroprolactinemia had PRL levels either within the normal range or only marginally elevated. From the immunoassays tested, PROL-CTK was the system which was less correlated with the Nb2 bioassay in group 2 (r=0.252; NS). Our experience is that macroprolactinemia is an asymptomatic condition in most of the cases. Therefore, we suggest that the routine measurement of PRL should be done with methods that are only minimally affected by the presence of macroprolactin. Such an approach would obviate the use of extensive, frequently expensive and ultimately useless diagnostic tests that are needed to determine the cause of the hyperprolactinemia.
Similar content being viewed by others
References
Suh H.K., Frantz A.G. Size heterogeneity of human prolactin in plasma and pituitary extracts. J. Clin. Endocrinol. Metab. 75: 928, 1974.
Guyda H.J. Heterogeneity of human growth hormone and prolactin secreted in vitro: immunoassay and radioreceptor assay correlations. J. Clin. Endocrinol. Metab. 41: 953, 1975.
Kiefer K.A., Malarkey W.B. Size heterogeneity of human prolactin in CSF and serum: experimental conditions that alter gel filtration patterns. J. Clin. Endocrinol. Metab. 46: 119, 1978.
Fang V.S., Refetoff S. Heterogenous human prolactin from a giant pituitary tumor in a patient with panhypopituitarism. J. Clin. Endocrinol. Metab. 47: 780, 1978.
Garnier P.E., Aubert M.L., Kaplan S.L., Grumbach M.M. Heterogeneity of pituitary and plasma prolactin in man: decreased affinity of “big” prolactin in a radioreceptor assay and evidence for its secretion. J. Clin. Endocrinol. Metab. 47: 1273, 1978.
Sinha Y. Prolactin variants. Trends Endocrinol. Metab. 3: 100, 1992.
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. 80: 2342, 1995.
Leite V., Cosby H., Sobrinho L.G., Fresnoza A., Santos M.A., Friesen H.G. Characterization of “big, big prolactin” (with comma) in patients with hyperprolactinemia. Clin Endocrinol. (Oxf.) 37: 365, 1992.
Hattori N., Ikekubo K., Ishihara T., Moridera K., Hino M., Kurahachi H. Effects of anti-prolactin autoantibodies on serum prolactin measurements. Eur. J. Endocrinol. 130: 434, 1994.
Bonhoff A., Vuille J.C., Gomez F., Gellersen B. Identification of macroprolactin in a patient with asymptomatic hyperprolactinemia as a stable PRL-IgG complex. Exp. Clin. Endocrinol. 103: 252, 1995.
Ahlquist J.A.O., Fahie-Wilson M.N. Variable detection of macroprolactin: a cause of apparent change in serum prolactin levels. Clin. Endocrinol. (Oxf.) 47: 629, 1997.
Bjøro T., Mørkrid L., Wergeland R., Turter A., Kvistborg A., Sand T., Torjesen P. Frequency of hyperprolactinemia due to large molecular weight prolactin (150-170 kD PRL). Scand. J. Clin. Lab. Invest. 55: 139, 1995.
Fahie-Wilson M.N., Soule S.G. Macroprolactinemia: contribution to hyperprolactinemia in district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann. Clin. Biochem. 34: 252, 1997.
Pereira M.C., Sobrinho L.G., Afonso A.M., Ferreira J.M., Santos M.A., Sousa M.F.F. Is idiopathic hyperprolactinemia a transitional stage towards prolactinoma? Obstet. Gynecol. 70: 305, 1987.
Whittaker P.G., Wilcox T., Lind T. Maintained fertility in a patient with hyperprolactinemia due to (big, big) prolactin (with comma). J. Clin. Endocrinol. Metab. 53: 863, 1981.
Andersen A.N., Pedersen H., Djursing H., Andersen B.N., Friesen H.G. Bioactivity of prolactin in a woman with excess of large molecular size prolactin, persistent hyperprolactinemia and spontaneous conception. Fertil. Steril. 38: 625, 1982.
Jackson R.D., Wortsman J., Malarkey W.B. Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses. J. Clin. Endocrinol. Metab. 61: 258, 1985.
Larrea F., Escorza A., Valero A., Hernandez L., Cravioto M.C., Diaz-Sanchez V. Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal ovarian function. J. Clin. Endocrinol. Metab. 68: 982, 1989.
Fraser I.A., Lun Z.G., Zhou H.P., Herington A, McCarron I., Tan K., Markham R. Detailed assessment of big big prolactin (without comma) in women with hyperprolactinemia and normal ovarian function. J. Clin. Endocrinol. Metab. 69: 585, 1989.
Author information
Authors and Affiliations
Additional information
These authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Cavaco, B., Prazeres, S., Santos, M.A. et al. Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays. J Endocrinol Invest 22, 203–208 (1999). https://doi.org/10.1007/BF03343542
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03343542