A case of macroprolactinemia?

I saw a 44-year-old woman last week in consultation for hyperprolactinemia. The diagnosis was made several years earlier by her gynecologist. She had had menometrorrhagia resulting in iron deficiency anemia. Her prolactin was elevated and she was started on bromocriptine. An MRI per the gynecologist’s progress note revealed subtle asymmetry of the pituitary suggesting possible microadenoma. Her prolactin levels normalized on the bromocriptine but she continued to have heavy menstrual bleeding. She later underwent hysterectomy.

Subsequently, her gynecologist relocated, and she stopped the bromocriptine for more than a year. Another physician retested her prolactin, found it to be 137 ng/mL, restarted the bromocriptine and sent her to me. Follow-up prolactin was 16.8 ng/mL after several weeks of therapy. She is on no drugs that could elevate prolactin, her thyroid function is normal, and there is no evidence of abnormalities of any of her other pituitary hormones. Her history was somewhat sketchy because few to none of the old records were available at the time of our initial visit.

The day after her visit, we received copies of some of the old records. Buried within them I found an old prolactin lab result from 2005. The measured serum prolactin level was 77.8 ng/mL (2.8-26.0). However, in fine print below this, there was a report of the polyethylene glycol-treated prolactin being normal at 11.2 ng/mL. A comment explaining this result suggested that she had macroprolactinemia. Nevertheless, this was either missed or ignored. Her bromocriptine dose was increased until the serum prolactin normalized.

In most individuals, prolactin circulates as the monomeric form. In others, larger than normal forms of prolactin occur and are indistinguishable on routine prolactin assays, resulting in higher than normal laboratory results. Macroprolactin has lower biologic activity than monomeric prolactin. Macroprolactinemia should be suspected in an individual with elevated serum prolactin but without symptoms. Precipitation with PEG is one screening method. Macroprolactin is precipitated by PEG, resulting in only the monomeric prolactin being measured. Chromatography may be used if PEG precipitation is indeterminate.

An important clue is that she had heavy prolonged menstrual bleeding rather than the amenorrhea or oligomenorrhea with light menstrual flow as we would usually expect. She also never had galactorrhea.

I will stop the bromocriptine and reevaluate the prolactin in the future. It is possible that she does not need to be on bromocriptine at all. Macroprolactinemia may cause falsely elevated prolactin levels, but in most patients it is without symptoms and does not require therapy.

I know this is a recurring theme in my posts, but I will repeat it yet again: We must never forget that we are treating patients and not numbers.