Macroprolactin

For the relatively large prolactinoma, see Macroprolactinoma.

Macroprolactin is the term used to describe complexed forms of the pituitary hormone prolactin which are found in blood. The most common complex found in blood consists of prolactin and immunoglobulin G (IgG).[1] While the free prolactin hormone is active, prolactin in the macroprolactin complex does not have any biological activity in the body and is considered benign.[2] However, macroprolactin is detected by all Laboratory tests that measure prolactin in blood.[3] This leads to misdiagnosis of hyperprolactinaemia in many people, especially those with other symptoms, such as infertility[4] or menstrual problems.[5]

"Macroprolactin" is most commonly a complex of prolactin and IgG (typically IgG4), displaying a molecular weight of approximately 150 kDa (which is hence 6–7 fold higher that the native molecule). Polymeric aggregate of highly glycosylated prolactin monomers or prolactin-IgA complexes (i.e. non-IgG-type macroprolactin) act similarly and also count as "macroprolactin".[6]

In patients with hyperprolactinemia, the serum pattern of prolactin isoforms usually encompasses 60%–90% monomeric prolactin, 15%–30% big-prolactin (40–60 kDa: usually prolactin dimers or big-big degradation products) and 0%–10% big-big prolactin (>100 kDa).[7] The condition of macroprolactinaemia is hence defined as predominance (i.e. >30%–60%) of circulating prolactin isoforms with molecular weight >100 kDa.[8]

There are certain chemicals, such as polyethylene glycol, that can be added to remove macroprolactin from a suspicious sample. The sample can then be re-analysed to see if the prolactin levels are still high. The gold standard test to diagnose macroprolactin is gel-filtration chromatography.

  1. ^ N Hattori, T Ishihara, K Ikekubo, K Moridera, M Hino, H Kurahachi (1992). "Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia". J Clin Endocrinol Metab. 75 (5): 1226–1229. doi:10.1210/jcem.75.5.1430082. PMID 1430082.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Wallace IR, Satti N, Courtney CH, Leslie H, Bell PM, Hunter SJ, McCance DR, Sheridan B, Atkinson AB. (2010). "Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinaemia establishes it as a benign variant". J Clin Endocrinol Metab. 95 (7): 3268–3271. doi:10.1210/jc.2010-0114. PMID 20427494.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Thomas P. Smith, Abdulwahab M. Suliman, Michael N. Fahie-Wilson, T. Joseph McKenna (2002). "Gross Variability in the Detection of Prolactin in Sera Containing Big Big Prolactin (Macroprolactin) by Commercial Immunoassays". J Clin Endocrinol Metab. 87 (12): 5410–5415. doi:10.1210/jc.2001-011943. PMID 12466327.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ K Jayakrishnan (December 2011). "chapter 11". Insights Into Infertility Management. JP Medical Ltd. p. 79. ISBN 9789350255186.
  5. ^ Fahie-Wilson MN, Smith TP. (2013). "Determination of prolactin: the macroprolactin problem". Best Practice & Research Clinical Endocrinology & Metabolism. 27 (5): 725–742. doi:10.1016/j.beem.2013.07.002. PMID 24094642.
  6. ^ Fahie-Wilson, Michael; Smith, Thomas P. (2013-10-01). "Determination of prolactin: The macroprolactin problem". Best Practice & Research Clinical Endocrinology & Metabolism. Endocrine Assays and Pitfalls - Volume I. 27 (5): 725–742. doi:10.1016/j.beem.2013.07.002. ISSN 1521-690X. PMID 24094642.
  7. ^ Lippi, Giuseppe; Plebani, Mario (2016-04-01). "Macroprolactin: searching for a needle in a haystack?". Clinical Chemistry and Laboratory Medicine. 54 (4): 519–522. doi:10.1515/cclm-2015-1283. ISSN 1437-4331. PMID 26845727. S2CID 5216254.
  8. ^ Fahie-Wilson, M N; John, R; Ellis, A R (2005-05-01). "Macroprolactin; high molecular mass forms of circulating prolactin". Annals of Clinical Biochemistry: International Journal of Laboratory Medicine. 42 (3): 175–192. doi:10.1258/0004563053857969. ISSN 0004-5632. PMID 15949152. S2CID 24997695.