The Impact on Clinical Practice of Routine Screening for Macroprolactin

Abstract

Prolactin (PRL) normally circulates in part as a high-molecular-weight form termed big-big PRL, which is a complex of PRL with an anti-PRL IgG autoantibody known as macroprolactin. Many patients with hyperprolactinemia resulting from macroprolactin lack classic hyperprolactinemic symptoms. Macroprolactin has reduced bioactivity in vivo. The investigators, working over 5 years at a single center, routinely screened for macroprolactin using the method of polyethylene glycol precipitation. The study population were individuals whose serum PRL exceeded the upper limit of the normal reference range (500 mU/L for females, 290 mU/L for males). Elevated plasma PRL levels were found in 2089 individuals, representing 21% of all samples analyzed. A majority of these samples contained more than 700 mU/L of total PRL. More than one fifth (22%) of hyperprolactinemic samples were accounted for by macroprolactin. This was the case more often for females than for males. Those with mild hyperprolactinemia (total PRL of 700 mU/L or less) more often had macroprolactinemia, but the proportion of clinically significant hyperprolactinemic samples accounted for by macroprolactin was comparable at all levels of total PRL. There were no differences in frequency of headache or infertility between patients with true hyperprolactinemia and those with macroprolactinemia, but galactorrhea and oligomenorrhea were more frequent in the former group. Although scans were done in similar proportions of patients, abnormalities were found mainly in the hyperprolactinemic group. Treatment with a dopamine agonist decreased serum prolactin levels in both groups; 15 of 19 treated women having true hyperprolactinemia and galactorrhea improved symptomatically. Macroprolactinemic patients had significantly higher plasma levels of estradiol than did those with true hyperprolactinemia, although there was overlap between the groups. Levels of luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio were significantly greater in macroprolactinemic patients. Macroprolactinemia is a common cause of elevated serum PRL. Routine screening of hyperprolactinemic individuals for macroprolactin may alter treatment in as many as one fifth of patients with hyperprolactinemia. Imaging is needed less often, as is dopamine agonist treatment, offsetting the added cost of screening and making the procedure cost-effective.