Background: The so called big-big prolactin, also known as macroprolactin is formed by prolactin-immunoglobulin complexes, and is considered to be biologically inactive. Nevertheless, macroprolactin may cause elevation of serum prolactin (Prl) concentrations measured by standard assays. In women presenting with oligo- and/or amenorrhoea the cause of menstrual irregularity needs to be explained even in the setting of concomitant macroprolactinaemia. We have therefore attempted to assess the prevalence of pituitary pathology in women with macroprolactinaemia and either oligo- or amenorrhoea.
Material & Methods: We performed pituitary MRI scans in 60 women with oligo- and/or secondary amenorrhoea aged 31.0±6.7 years (mean±SD), range 1845 years, who were found to have raised Prl concentrations due to macroprolactinaemia (detected by the polyethylene glycol (PEG) precipitation method).
Results: Pituitary microadenomas were detected in 9/60 (15%) and pituitary macroadenomas in 3/60 (5%) of women with macroprolactinaemia. In all of these cases we also observed elevated concentrations of free Prl (i.e. above 530 mIU/L), even after PEG precipitation. The highest value of free Prl was in a case of a microadenoma (total Prl 19207 mIU/L, free Prl after PEG precipitation 7738 mIU/L), while in the case of a macroadenoma the highest concentration of free Prl was 2798 mIU/L (total Prl 7441 mIU/L before PEG precipitation). Final diagnosis in the remaining patients included PCOS - 39 cases (65%), premature ovarian failure - 3 cases (5%) and hypothalamic amenorrhoea - 5 cases (8.3%)).
Conclusions: Hyperprolactinaemia and macroprolactinaemia may coexist in the same patient. Pituitary micro- or macroadenomas can be found in up to 20% of women with macroprolactinaemia and oligo-/amenorrhoea. If the concentration of free prolactin is raised after PEG precipitation, then further endocrine assessment including pituitary magnetic resonance imaging is mandatory.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.