Macroprolactinaemia: prevalence and aetiologies in a large group of hospital workers

P>Objective Macroprolactinaemia is one of the causes of hyperprolactinaemia and often leads to misdiagnosis and inappropriate treatment, but the aetiologies are unclear. The objective of the study was to determine the prevalence of macroprolactinaemia in a healthy population and to investigate the mechanisms underlying the development of macroprolactin. Design Observational study of the prevalence, causes, mechanisms and diagnosis of disease using excess sera after hepatitis B virus screening tests at a hospital in Japan. Participants A total of 1330 hospital workers (1010 women and 320 men) participated in this study. Measurements Macroprolactinaemia was screened using the polyethylene glycol (PEG) precipitation method. Sera containing macroprolactin were further examined by binding studies for possible aetiologies. Results Of the 1330 subjects, 49 (3 center dot 68%) were diagnosed with macroprolactinaemia. The frequency of hyperprolactinaemia in untreated samples in subjects with macroprolactinaemia (30 center dot 6%) was significantly higher than in individuals without macroprolactinaemia (2 center dot 26%). Of the 49 subjects with macroprolactinaemia, all had a normal monomeric PRL concentration following PEG removal of macroprolactin. Of 44 hyperprolactinaemias found, 15 (34 center dot 1%) had macroprolactinaemia. IgG-bound prolactin was detected in all sera containing macroprolactin. The levels of IgG-bound prolactin positively correlated with those of macroprolactin, suggesting that IgG-bound prolactin forms macroprolactin. Approximately three quarters of the subjects with macroprolactinaemia had anti-prolactin autoantibodies. Glycosylation, aggregation and covalent/noncovalent binding were also involved in the formation of macroprolactin. Conclusions Macroprolactinaemia is a common disorder and causes hyperprolactinaemia in a healthy population. The major aetiology of macroprolactin in our subjects was complexes of prolactin-IgG comprising mainly anti-prolactin autoantibodies, and other minor complex prolactin species.