macroprolactin

{{short description|Inactive form of prolactin}}

{{Refimprove|date=June 2012}}

{{For|the relatively large prolactinoma|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).{{Cite journal |last=N Hattori, T Ishihara, K Ikekubo, K Moridera, M Hino, H Kurahachi |date=1992 |title=Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia. |url=https://academic.oup.com/jcem/article-abstract/75/5/1226/2651169?redirectedFrom=fulltext&login=true |journal=J Clin Endocrinol Metab |volume=75 |issue=5 |pages=1226–1229|doi=10.1210/jcem.75.5.1430082 |pmid=1430082 |url-access=subscription }} 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.{{Cite journal |last=Wallace IR, Satti N, Courtney CH, Leslie H, Bell PM, Hunter SJ, McCance DR, Sheridan B, Atkinson AB. |date=2010 |title=Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinaemia establishes it as a benign variant. |journal=J Clin Endocrinol Metab |volume=95 |issue=7 |pages=3268–3271|doi=10.1210/jc.2010-0114 |pmid=20427494 }} However, macroprolactin is detected by all Laboratory tests that measure prolactin in blood.{{Cite journal |last=Thomas P. Smith, Abdulwahab M. Suliman, Michael N. Fahie-Wilson, T. Joseph McKenna |date=2002 |title=Gross Variability in the Detection of Prolactin in Sera Containing Big Big Prolactin (Macroprolactin) by Commercial Immunoassays |url=https://academic.oup.com/jcem/article/87/12/5410/2823581 |journal=J Clin Endocrinol Metab |volume=87 |issue=12 |pages=5410–5415|doi=10.1210/jc.2001-011943 |pmid=12466327 |url-access=subscription }} This leads to misdiagnosis of hyperprolactinaemia in many people, especially those with other symptoms, such as infertility{{Cite book|title=Insights Into Infertility Management |author=K Jayakrishnan |chapter-url=https://books.google.com/books?id=vk582FjaeZMC&dq=Macroprolactin+Size-exclusion+chromatography&pg=PT100| publisher= JP Medical Ltd.| page=79| chapter=chapter 11|date=December 2011 |isbn=9789350255186 }} or menstrual problems.{{Cite journal |last=Fahie-Wilson MN, Smith TP. |date=2013 |title=Determination of prolactin: the macroprolactin problem. |journal=Best Practice & Research Clinical Endocrinology & Metabolism |volume=27 |issue=5 |pages=725–742|doi=10.1016/j.beem.2013.07.002 |pmid=24094642 }}

"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".{{Cite journal |last1=Fahie-Wilson |first1=Michael |last2=Smith |first2=Thomas P. |date=2013-10-01 |title=Determination of prolactin: The macroprolactin problem |url=https://www.sciencedirect.com/science/article/pii/S1521690X13001103 |journal=Best Practice & Research Clinical Endocrinology & Metabolism |series=Endocrine Assays and Pitfalls - Volume I |language=en |volume=27 |issue=5 |pages=725–742 |doi=10.1016/j.beem.2013.07.002 |pmid=24094642 |issn=1521-690X|url-access=subscription }}

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).{{Cite journal |last1=Lippi |first1=Giuseppe |last2=Plebani |first2=Mario |date=2016-04-01 |title=Macroprolactin: searching for a needle in a haystack? |journal=Clinical Chemistry and Laboratory Medicine |language=en |volume=54 |issue=4 |pages=519–522 |doi=10.1515/cclm-2015-1283 |pmid=26845727 |s2cid=5216254 |issn=1437-4331|doi-access=free }} The condition of macroprolactinaemia is hence defined as predominance (i.e. >30%–60%) of circulating prolactin isoforms with molecular weight >100 kDa.{{Cite journal |last1=Fahie-Wilson |first1=M N |last2=John |first2=R |last3=Ellis |first3=A R |date=2005-05-01 |title=Macroprolactin; high molecular mass forms of circulating prolactin |url=http://journals.sagepub.com/doi/10.1258/0004563053857969 |journal=Annals of Clinical Biochemistry: International Journal of Laboratory Medicine |language=en |volume=42 |issue=3 |pages=175–192 |doi=10.1258/0004563053857969 |pmid=15949152 |s2cid=24997695 |issn=0004-5632|url-access=subscription }}

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.