Macroprolactin has reduced bioactivity in vivo and accumulates in the sera of some subjects resulting in pseudo-hyperprolactinemia and consequent misdiagnosis. We have audited our experience of routine screening for macroprolactin using PEG precipitation over a 5-year period in a single center.

Application of a reference range for monomeric prolactin (the residual prolactin present in macroprolactin depleted serum) for normal individuals revealed that 453 of 2089 hyperprolactinemic samples (22%) identified by Delfia immunoassay were explained entirely by macroprolactin. The percentage of hyperprolactinemic samples explained by macroprolactinemia was similar across all levels of total prolactin (18%, 21%, 19% and 17% of samples from 700-1000, 1000-2000, 2000-3000 and greater than 3000mU/L respectively). Application of an absolute PRL threshold following PEG treatment of sera, rather than the traditional method, i.e. < 40% recovery, minimizes the opportunity for misclassification of patients where macroprolactin accounted for > 60% of PRL and the residual bioactive prolactin was present in excess.

Macroprolactinemic patients could not be differentiated from true hyperprolactinemic patients on the basis of clinical features alone. While oligomenorrhea/amenorrhea and galactorrhea were more common in patients with true hyperprolactinemia (P < 0.05), they were also frequently present in macroprolactinemic patients. Plasma levels of estradiol and LH and the LH/FSH ratio were significantly greater in macroprolactinemic compared with true hyperprolactinemic subjects (P < 0.05). Reduced use of imaging and dopamine agonist prescription resulted in a net cost saving offsetting the additional cost associated with the introduction of screening. Routine screening of all hyperprolactinemic sera for macroprolactin is recommended.