Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes

Objective: Macroprolactinemia, which can be detected by a polyethylene glycol (PEG) precipitation test, is a clinically and biologically heterogeneous condition. In this study, we analyzed whether the clinical presentation, the hormonal findings and the in vitro lactogenic activity differed between macroprolactinemic patients with and without circulating prolactin (PRL)-IgG complexes. Design: Clinical data were reviewed and additional hormonal studies were performed in 50 hyperprolactinemic patients with macroprolactinemia. Methods: Macroprolactinemia was identified by a PRL recovery after PEG precipitation of < 50%, as measured by an automated commercial immunoassay system and circulating PRL-IgG complexes by an abnormal PRL binding to anti-IgG agarose. Results: PRL-IgG complexes were found in 46 patients. The origin of hyperprolactinemia in these 46 patients was idiopathic in 33 patients, while a pituitary lesion or stalk magnetic resonance imaging or computed tomography scan was detected in 13 patients found compression. Galactorrhea was found in 11 of these 46 patients, while this condition was present in three of the four patients without circulating PRL-IgG complexes. The median free PRL concentration was significantly lower in patients with PRL-IgG complexes than in the group without complexes (243 vs 969 mIU/l; P < 0.005), whereas median total PRL immunoreactivity and median PRL bioactivity in the Nb2 assay were not significantly different. In patients with circulating PRL-IgG complexes, Nb2 bioassay results correlated significantly with total PRL immunoreactivity (r = 0.64; P < 0.0001), but not with free PRL results (r = 0.24; P < 0.17). Conclusions: These results indicate that PRL-IgG complexes (i) account for most cases of macroprolactinemia - as identified by PEG precipitation - in hyperprolactinemic patients presenting with a variety of diagnoses, (ii) are not associated with a specific clinical presentation, (iii) can be found in patients with diverse pituitary pathologies, and (iv) possess an in vitro lactogenic activity in the Nb2 bioassay in relation to their immunoreactivity.