Macroprolactinaemia: validation and application of the polyethylene glycolprecipitation test and clinical characterization of the condition

OBJECTIVE The clinical characteristics and natural history of macroprolacti naemia are yet to be fully established and there is currently no widely acc epted simple in vitro test for routine identification of the condition, Thi s study was designed to further validate the polyethylene glycol (PEG) prec ipitation test with assessment of percentage prolactin recovery (%R), for t he detection of macroprolactinaemia and clinically characterize cases ident ified using the test, DESIGN Analytical validation and application of the PEG precipitation test for diagnosis of macroprolactinaemia and a retrospective case-notes review of some of the patients identified with the condition, PATIENTS Sera from 188 patients with elevated serum prolactin (PRL) concent rations were screened for macroprolactinaemia, Seventeen of the patients wh o were under follow-up at the local teaching hospital and were identified t o have macroprolactinaemia were systematically characterized clinically, MEASUREMENTS Prolactin was measured in sera, fractions from gel filtration chromatography and supernatant obtained after PEG precipitation, by the DEL FIA fluoroimmunoassay, CLINICAL ENDPOINTS Initial serum PRL and symptoms an d their response to dopamine agonist therapy; imaging of the pituitary glan d; serum PRL and symptoms after cessation of dopamine agonist therapy; cour se of serum PRL and symptoms without dopamine agonist therapy, RESULTS The within-batch coefficient of variation (CV) of the PEG precipita tion test ranged between 2.8 and 7.3% while the between-batch CV ranged bet ween 3.4 and 9.7%. Intra-individual variability up to five months was 9.9%. A prolactin recovery less than or equal to 40% was indicative of macroprol actinaemia, while the condition was unlikely to be present at values > 50%. The prevalence of macroprolactinaemia was 15% without sex difference, Clin ical characterization of 17 patients showed modest initial serum PRL concen trations and there was imaging evidence of a coexisting pituitary adenoma i n three of them, Dopamine agonist therapy resulted in substantial falls in serum PRL and this was associated with improvement or resolution of symptom s in some patients, Stoppage of dopamine agonist resulted in rebound hyperp rolactinaemia in all cases, Spontaneous improvement in symptoms occurred in three patients but hyperprolactinaemia persisted in all those who were not on treatment. CONCLUSIONS The PEG precipitation test with assessment of 'free' prolactin has been shown to be reproducible and sensitive for the detection of macrop rolactinaemia, Many of the patients who had macroprolactinaemia presented w ith at least one symptom of the hyperprolactinaemic syndrome. Dopaminergic therapy may influence the course of both serum PRL and symptoms in some of these patients.