Background: Measurement of serum prolactin is a key laboratory test for the differential diagnosis of amongst others pituitary mass, subfertility problems and menstrual disturbances. Prolactin methods are known to be poorly standardized. On top of that, we observed in several cases elevated prolactin levels in laboratories using the Cobas assay and levels within the reference interval (RI) when the same samples were measured in another laboratory using the Atellica assay. This suggests that not all RI used for prolactin are appropriate. Therefore more insight in between-method differences is needed and RI for prolactin need to be re-established.

Methods: Method comparisons were performed in 30 leftover serum samples using two prolactin immunoassays (Atellica (Siemens) and Cobas (Roche)). In addition, RI for prolactin were established in serum from healthy volunteers (men, premenopausal and postmenopausal women; n=366) using the Atellica. Post-menopausal state was confirmed by a serum FSH of >30U/L.

Results: Prolactin levels measured using the Cobas were 1.7 times higher compared to the Atellica. This difference was not reflected in the RI stated in the kit insert, which is often used by laboratories. Current RIs were for Atellica and Cobas respectively men < 0.30 U/L, <0.37 U/L; premenopausal women <0.60 U/L, <0.62 U/L; post-menopausal women <0.40 U/L, <0.43 U/L. The newly established RI using the Atellica were men < 0.32 U/L; premenopausal women <0.64 U/L and post-menopausal women <0.31 U/L.

Discussion: We showed significant differences between prolactin methods from two vendors and established new RI for prolactin for the Atellica. These data explain the cases mentioned in the introduction and confirm the appropriateness of the Atellica RI. Standardization differences and improper RI of prolactin methods may result in incorrect interpretation of prolactin levels in clinical diagnostics. We highly recommend laboratory specialists to review their prolactin RI in their own laboratory in order to accurately interpret prolactin results.