Prevalence of macroprolactin in serum (>40%) can be a cause of asymptomatic hyperprolactinemia. However, there is still lack of evidence how to manage with symptomatic patients with macroprolactinemia.
We analyzed clinical data and monomeric prolactin levels in 85 women of reproductive age with hyperprolactinemia: NonTumor hyperprolactinemia (NT, n=31), MIcroadenomas (MI, n=32), MAcroadenomas (MA, n=22). Prolactin levels 1716 [1150; 2700] mIU/l; 2974 [1190; 3665] mIU/l and 3546 [1312; 48209] mIU/l, accordingly.
Prevalence of macroprolactin in serum was found in 16/31 (51.6%) NT, 9/32 (28.1%) MI, and 2/22 (9%) MA (a relative amount macroprolactin was 79 [75; 88] %). Among patients with macroprolactinemia normal levels of monomeric prolactin were found in 10/16 NT, 4/9 MI and 1/2 MA; all patients with normal monomeric prolactin levels had total prolactin levels <5000 mIU/l; only 6 NT and 4 MI were asymptomatic, other patients had menstrual irregularities and/or infertility and non-hyperprolactinemic reasons for these clinical symptoms were found after investigations.
Biological activity of hyperprolactinemic sera (as a proliferative response of Nb2 rat lymphoma cells) was evaluated in vitro in 8 patients with predominance of monomeric prolactin and in 5 patients with macroprolactiemia. Ratio Prolactin Immunoreactivity/Prolactin Bioactivity varied 0.881.1 and 1.462.26 in these subgroups accordingly. Hence lower biological activity of hyperprolactinemic sera with the predominance of macroprolactin was proven.
Thus in cases of macroprolactinemia normal monomeric prolactin levels (with proven low biological activity of serum) can coexist with menstrual disorders and/or infertility due to other reasons, and mimic true hyperprolactinemic conditions. Some of patients with macroprolactinemia also had pituitary incidentaloma. To avoid misinterpretation of clinical and hormonal data we support assessing for macroprolactin in all patients with total prolactin levels <5000 mIU/l regardless of symptoms.