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

Abstract

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 ¼ 0.64; P , 0.0001), but not with free PRL results (r ¼ 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.

Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in macroprolactinemia

“…We previously reported a patient with macroprolactinemia who had a highly glycosylated PRL, but did not have anti-PRL autoantibodies (Hattori 1996). Therefore, macroprolactinemia is a heterogeneous entity, although many subjects have anti-PRL autoantibodies as shown in this study and other reports (Cavaco et al 1995, De Schepper et al 2003.…”

“…Several groups and ourselves have identified anti-PRL autoantibodies in the sera from patients with macroprolactinemia (Hattori et al 1992, Cavaco et al 1995, Pascoe-Lira et al 2001, De Schepper et al 2003, though much remains unknown about their biological significance. In this study, we examined autoantibody-binding sites (epitopes) on the PRL molecule using PRLdeletion mutants, and compared them with the binding sites to PRL receptors to clarify the effects of the autoantibodies on the PRL bioactivity.…”

Macroprolactinaemia: a biological diagnostic strategy from the study of 222 patients

“…The prevalence of MPRL has been estimated at being between 10 and 45% in the hyperprolactinaemic population (2,5,6,10). In most cases, bbPRL is composed of immune complexes of PRL and anti-PRL auto-antibodies (IgG) (7,11,12,13). The subsequent hyperprolactinaemia may be attributed to a diminished clearance rate, due to the high molecular size of these bbPRL complexes (11).…”

The natural history of macroprolactinaemia

“…The prevalence of macroprolactinaemia is estimated to be 10-26% in patients with hyperprolactinaemia (4,5,6,7,8,9) and 3.68% in the general population (10). MacroPRL is mainly a complex of PRL with IgG, especially anti-PRL autoantibodies (3,10,11,12,13,14,15). Hyperprolactinaemia is more frequently observed in subjects with macroprolactinaemia probably because there is a delayed clearance of macroPRL due to the large molecular size (10,16).…”