LAUSR

The recent survey of UK clinical biochemistry laboratories by McKeeman et al. revealed considerable variation in reflex and reflective testing practice. As regards testing for macroprolactinaemia (hyperprolactinaemia due to macroprolactin with normal monomeric prolactin), the survey showed that a substantial minority of laboratories do not test, while others test only when the serum prolactin concentration is substantially elevated. The survey authors point out that current best practice recommends that laboratories should introduce screening procedures to exclude macroprolactinaemia in all patients with hyperproplactinaemia, but the two cited recommendations advocate different approaches, reflecting the variation in practice found in the survey. Our study, published in 2013, included a review of the literature which revealed overwhelming evidence that failure to recognize macroprolactinaemia leads to misdiagnosis, mismanagement of patients, waste of healthcare resources and unnecessary concern for both patient and clinician. On the basis of this, we proposed that laboratories should introduce a screening protocol for the detection of macroprolactinaemia in all cases of hyperprolactinaemia and that this should be recognized as best practice in both clinical and laboratory guidelines. To our knowledge, this proposal has not been challenged. The All-Wales Clinical Biochemistry Audit Group instead advocates the use of manufacturer-specific and gender-related reference intervals and advises screening for macroprolactinaemia only when prolactin is 700mU/L or greater. Thus, not all cases of hyperprolactinaemia are screened. No evidence is presented for this approach and no advice is provided on how a prolactin result above the upper limit of the reference range but below the cut-off for screening should be reported. In our experience, most cases of macroprolactinaemia result in modestly elevated prolactin concentrations and consequently will be missed with this approach and by the even higher screening thresholds commonly in use in the UK revealed in the survey. In a recent study, Sostaric et al. found that more than half of patients with elevated prolactin due to macroprolactinemia were not correctly identified when a screening threshold of 700mU/L was employed. Moreover, raising the screening threshold to 1000mU/L failed to identify 85% of the patients with macroprolactinemia. On the basis of these findings, the authors concluded that all samples with prolactin concentration above the upper limit of the manufacturer’s reference interval should be submitted to PEG precipitation. McKeeman et al. identify a need to harmonize reflex and reflective testing practice in the UK by obtaining consensus, based on evidence of best practice. To this end, we would welcome an evidence-based discussion of best practice in harmonizing screening for macroprolactinaemia.