Frequent Misdiagnosis and Mismanagement of Hyperprolactinemic Patients before the Introduction of Macroprolactin Screening: Application of a New Strict Laboratory Definition of Macroprolactinemia

Macroprolactin (big big prolactin) has reduced bioactivity and is measured by immunoassays for prolactin when it accumulates in the plasma of some individuals. We applied normative data for serum prolactin after treatment of sera to remove macroprolactin to elucidate the contribution of macroprolactin to misleading diagnoses, inappropriate investigations, and unnecessary treatment. We reviewed records of women attending a tertiary referral center who had prolactin >1000 mIU/L. Application of a reference interval to polyethylene glycol (PEG)-treated hyperprolactinemic sera identified 21 patients in whom hyperprolactinemia was accounted for entirely by the presence of macroprolactin. Presenting clinical features, diagnoses, and treatment were compared in these patients and 42 age-matched true hyperprolactinemic patients. Prolactin concentrations in sera of 110 healthy individuals ranged from 78 to 564 mIU/L. The range of values for the sera after PEG treatment was 70-403 mIU/L. For macroprolactinemic samples, PEG treatment decreased mean (SD) prolactin from 1524 (202) mIU/L to 202 (27) mIU/L but decreased it only from 2096 (233) mIU/L to 1705 (190) mIU/L in true hyperprolactinemic patients (P