A more rigorous laboratory definition of macroprolactinaemia with clinical significance
TP Smith, J Gibney, L Kavanagh, A Dickinson & TJ McKenna
The importance of the differentiation between the apparent benign clinical condition of macroprolactinaemia and that of true hyperprolactinaemia, which requires therapy, is becoming widely recognised. Laboratories routinely rely on prolactin recoveries of less than 40 percent following treatment of sera with polyethylene glycol (PEG) to distinguish between the former and latter conditions. However, the 40 percent threshold employed is arbitrarily defined with little scientific basis. The aim of this study was to establish a reference range for PEG treated normal sera and to assess its use relative to the widely used 40 percent threshold in routine clinical practice.Sera from 110 normal healthy females, were analysed before and after treatment with PEG. Prolactin levels in untreated sera ranged from 78 to 564mU/L (Mean 249;SD 107). Treatment with PEG resulted in a decrease in prolactin levels in all sera to yield a range of 70-403mU/L (Mean 197;SD 80). Recoveries following PEG were variable and ranged from 56 to 95 percent. For a diagnosis of macroprolactinemia to be attributed to a patient, PEG treatment of sera should correct the hyperprolactinemia to levels obtained in normoprolactinemic sera following PEG treatment i.e. less than 403mU/L.We report 5 patients with serum prolactin ranging from 3,145 to 19,050mU/L, who retained significant residual true hyperprolactinaemia (serum prolactin greater than 1,000mU/L) following PEG treatment. The 5 patients exhibited serum prolactin recoveries following PEG treatment of 16 to 37 percent and hence would all have been misdiagnosed as macroprolactinaemic had the 40 percent cut-off been employed.The application of an appropriate reference range, rather than percent recovery, to the PEG immunoprecipitation procedure allows a more rigorous, scientific and standardised approach to the laboratory diagnosis of macroprolactinaemia with enhanced diagnostic sensitivity and specificity.