Laboratories occasionally get questions from clinicians about prolactin results, mainly to either rule out high-dose hook effect or assess interference from macroprolactin. In most laboratories, sandwich immunoassay is used to measure prolactin concentration and it is widely known that older generations of prolactin assays suffer from hook effect and interference from macroprolactin. In the presence of extremely high concentration of prolactin, antibodies can be saturated, resulting in falsely low results, which is known as high-dose hook effect. Multiple cases have been reported in patients with giant prolactinomas, that their prolactin results were measured as normal or moderately elevated. In order to rule out high-dose hook effect, clinicians normally request laboratories to perform appropriate dilutions for prolactin in patients with large pituitary tumors. Newer generation of prolactin assays have better performance in this aspect, and most assays nowadays have no hook effect up to concentrations of 10,000 ng/mL, claimed by manufactures.
Another pitfall of prolactin assay is the interference from macroprolactin. Macroprolactin is a complex of prolactin bound to immunoglobulin, and thought to be biologically inactive. In the presence of elevated macroprolactin, patient is asymptomatic. However, macroprolactin can be picked up by prolactin immunoassays to some extent, and results in misdiagnosis as hyperprolactinemia. Reports showed that 15-20% of cases with hyperprolactinemia was due to elevated macroprolactin. Therefore, macroprolactinemia should be considered while evaluating hyperprolactinemia cases in the absence of symptoms or pituitary imaging evidence. Laboratories could easily perform dilution study to test if interference exists. To confirm the presence of macroprolactin, polyethylene glycol (PEG) 6000 can be used to precipitate macroprolactin followed by prolactin measurement in the supernatant. The presence of macroprolactin is suggested when the pull-down percentage is greater than 40-50%. This test is offered by many reference laboratories.
These two pitfalls of prolactin biochemistry assays should always be kept in mind by laboratorians, to provide better guidance to clinicians’ concern and workups on prolactin related cases.
-Xin Yi, PhD, DABCC, FACB, is a board-certified clinical chemist, currently serving as the Co-director of Clinical Chemistry at Houston Methodist Hospital in Houston, TX and an Assistant Professor of Clinical Pathology and Laboratory Medicine at Weill Cornell Medical College.