Hyperprolactinaemia and Macroprolactin

Hyperprolactinaemia:

Hyperprolactinaemia may result from hypothalamic and pituitary disorders, stress, nipple stimulation, pregnancy, primary hypothyroidism, chronic renal failure, cirrhosis and polycystic ovary syndrome, from drugs such as anti-psychotics, antiemetics (eg metoclopramide), antidepressants, opiates and antihypertensives (methyldopa, reserpine and verapamil). Spurious hyperprolactinemia can occur because of cross-reaction or interferences in a prolactin assay; for example by macroprolactin, heterophile antibodies or rheumatoid factors.

A prolactin level > 5000 mIU/L is highly suggestive of a prolactinoma.

Macroprolactin:

Prolactin assay methods are subject to interference from high molecular weight variants, including macroprolactin. This means that raised prolactin levels may occasionally be due to macroprolactin in the plasma and not to hyperprolactinaemia in the patient. This occurs in up to 7 percent of samples measured using the Beckman Coulter Access prolactin assay that is used in Endolab. Frequencies of up to 25 percent have been reported for some other analyser methods. Endolab procedures include the automatic screening of all raised prolactin samples using the PEG test, which removes macroprolactin. In this situation, reports will include:

Prolactin (total). This is the concentration before PEG treatment.
Prolactin (free). This is the concentration following PEG, and is considered to reflect biologically active hormone.
Macroprolactin. This is reported as undetectable, low or moderate-high levels. Note though that the PEG test is not specific, so that rheumatoid factor and heterophile antibodies, for example, may also be reported as "macroprolactin".

Requisition forms asking for Macroprolactin or for Free Prolactin will have both tests reported regardless of prolactin level.

Current consensus opinion is that patients with macroprolactin and a normal level of prolactin (free) who do not have clinical features of hyperprolactinaemia or a pituitary mass lesion, do not warrant further investigation, eg MRI imaging.

Bibiography

Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access prolactin assay. Ellis MJ, Livesey JH, Soule SG. Clinical Biochemistry 39: 1028-34 (2006).

Cross-reactivities of macroprolactin and big-prolactin in three commercial immunoassays for prolactin: A chromatographic analysis. Ellis MJ, Reed MR and Livesey JH. Clinical Biochemistry 40:1285-90 (2007).

Prolactin immunoreactivity in rheumatoid factor-containing specimens: is it prolactin, macroprolactin or assay interference? Ellis MJ, Livesey JH, Soule SG. The Open Clinical Chemistry Journal 1:38-41 (2008).

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