Macroprolactin: the Role of Serial Measurement Throughout Pregnancy

Abstract

Introduction: Prolactin circulates predominantly as a 23 kDa monomer, and a high molecular weight form largely consisting of a complex of prolactin and anti-prolactin IgG autoantibody called macroprolactin. The latter cross-reacts with conventional laboratory assays for prolactin.

We here describe the use of serial macroprolactin measurement to assist in the management of a pregnant lady with pre-conception hyperprolactinaemia in whom a magnetic resonance imaging scan had not been performed.

Case Report: A 24-year old lady was found to have a raised prolactin level of 2 332 mu/L (reference range: 40–530 mu/L). Prolactin was checked because of primary infertility. Macroprolactin screening was positive, accounting for 54% of measured prolactin (estimated monomeric prolactin=1 073 mu/L).

As expected, measured prolactin levels rose through pregnancy to 6 975 mu/L at 20 weeks and to 8 374 mu/L at 36 weeks gestation.

Adjustment for macroprolactin and big prolactin gave estimated monomeric prolactin levels of 2 370 mu/L at 16 weeks (macroprolactin/big prolactin=66%), 2 441 mu/L at 20 weeks (macroprolactin/big prolactin=65%) and 2 596 mu/L at 36 weeks (macroprolactin/big prolactin=69%). Thus, adjusted prolactin fell within the reference range for pregnancy at these points.

Gel filtration chromatography was performed on the 20-week (second trimester) sample and compared with the pre-pregnancy sample. The pattern remained similar but all components were increased in the second trimester sample (including the monomeric, big prolactin and macroprolactin forms).

Conclusion: In this case report, serial measurement of macroprolactin with estimation of monomeric prolactin enhanced clinical management throughout pregnancy, saving unnecessary further investigations and avoiding unnecessary distress for the patient.

Key words

macroprolactin - hyperprolactinaemia - pregnancy - case

• References

• 1 Riddle O, Bates R, Dyshorn S. The preparation, identification and assay of prolactin – a hormone of the anterior pituitary. Am J Physiol 1933; 105: 191-216
• 2 Hwang P, Guyda H, Friesen H. Purification of human prolactin. J Biol Chem 1972; 247: 1955-1958
• 3 Suh HK, Frantz AG. Size heterogeneity of human prolactin in plasma and pituitary extracts. J Clin Endocrinol Metab 1974; 39: 928-935
• 4 Schiettecatte J, De Schepper J, Velkeniers B, Smitz J, Van Steirteghem A. 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
• 5 Leite V, Cosby H, Sobrinho LG, Fresnoza MA, Santos MA, Friesen HG. Characterization of big, big prolactin in patients with hyperprolactinaemia. Clin Endocrinol 1992; 37: 365-372
• 6 Cavaco B, Prazeres S, Santos MA, Sobrinho LG, Leite V. Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays. J Endocrinol Invest 1999; 22: 203-208
• 7 Rogol AD, Rosen SW. Prolactin of apparent large molecular size: the major immunoactive prolactin component in plasma of a patient with a pituitary tumor. J Clin Endocrinol Metab 1974; 38: 714-717
• 8 Whittaker PG, Wilcox T, Lind T. Maintained fertility in a patient with hyperprolactinaemia due to big, big prolactin. J Clin Endocrinol Metab 1981; 53: 863-866
• 9 Gibney J, Smith TP, McKenna TJ. Clinical relevance of macroprolactin. Clin Endocrinol 2005; 62: 633-643
• 10 Gibney J, Smith P, McKenna TJ. The Impact on Clinical Practice of Routine Screening for Macroprolactin. J Clin Endocrinol Metab 2005; 90: 3927-3932
• 11 Fraser IS, Lun ZG, Zhou JP, Herington AC, McCarron G, Caterson I. Detailed assessment of big big prolactin in women with hyperprolactinemia and normal ovarian function. J Clin Endocrinol Metab 1989; 69: 585-592
• 12 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
• 13 O’Leary P, Boyne P, Flett P, Beilby J, James I. Longitudinal assessment of changes in reproductive hormones during normal pregnancy. Clin Chem 1991; 37: 667-672
• 14 Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 2009; 114: 1326-1331
• 15 Larrea F, Escorza A, Valero A, Hernandez L, Cravioto MC, Diaz-Sanchez V. Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal ovarian function. J Clin Endocrinol Metab 1989; 68: 982-987
• 16 Diver MJ, Ewins DL, Worth RC, Bowles S, Ahlquist JA, Fahie-Wilson MN. An unusual form of big, big (macro) prolactin in a pregnant patient. Clin Chem 2001; 47: 346-348
• 17 Hattori N. The frequency of macroprolactinemia in pregnant women and the heterogeneity of its etiologies. J Clin Endocrinol Metab 1996; 81: 586-590
• 18 Heald AH, Blantern E, Anderson SG, Radford D, Qureshi Z, Nair S. Quantitative adjustment for macroprolactin is an integral part of laboratory assessment of hyperprolactinaemia. Exp Clin Endocrinol Diabetes 2012; 120: 376-380
• 19 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