False-positive polyethylene glycol precipitation tests for macroprolactin due to increased serum globulins

Background The polyethylene glycol (PEG) precipitation test is widely used to detect hyperprolactinaemia caused by macroprolactin. We report two cases of hyperprolactinaemia in which a low recovery of serum prolactin (PRL) after PEG precipitation indicated the presence of macroprolactin, but no macroprolactin was detected by gel filtration chromatography (GFC). Both cases had elevated concentrations of serum globulin (IgG myeloma and polyclonal hypergammaglobulinaemia due to human immunodeficiency virus [HIV] infection), which prompted us to investigate further the effect of serum globulin on the specificity of the PEG precipitation procedure. Methods The effect of increasing concentrations of gamma globulin on the precipitation of PRL by PEG was studied by adding purified human gamma globulin to serum. Ten samples from HIV-infected patients, which showed a low recovery of PRL after PEG precipitation (<60%) were studied with GFC. Results Addition of gamma globulin decreased the recovery of PRL following precipitation with PEG and gamma globulin concentrations correlated inversely with PRL concentrations ( r = 0.9429, P < 0.0167) and percentage recovery of PRL ( r = −1.000, P < 0.005). Only one out of 10 samples from HIV-infected patients with PRL recoveries of <60% following PEG precipitation showed a substantial macroprolactin component on GFC. Conclusions Monomeric PRL is co-precipitated with serum globulins by PEG. Increased serum globulin concentrations can increase the amount of monomeric PRL precipitated by PEG giving a false estimate of the monomeric PRL and the erroneous impression that macroprolactin is present. The results of the PEG precipitation test should be interpreted with caution in patients with elevated serum globulin concentrations.