Two pitfalls have frequently been reported for prolactin assays: the "hook" effect may yield false-negative results when the prolactin concentration is very high (1); and the presence in serum of a high proportion of a biologically inactive but immunologically reactive form of prolactin (macroprolactin) may yield false-positive results (2).
It is well recognized that circulating prolactin may exist in several forms, including little (monomeric), big, and big, big (macroprolactin) prolactin with molecular masses of 23, 50, and 150-170 kDa, respectively (1).
(1) presented two clinical cases demonstrating the diagnostic confusion created by cases of hyperprolactinemia that are attributable to the presence of macroprolactin. The authors urged manufacturers of prolactin (PRL) reagents to (a) indicate in their product literature the extent to which macroprolactin interferes in their assays, and (b) have available a validated method to confirm the presence of macroprolactin.
Macroprolactin is a complex of prolactin with immunoglobulin (IgG) that in vivo appears to have limited or no biological activity, possibly because of the failure of the high-molecular weight complex to cross capillary walls (1).
Serum macroprolactin concentrations were sought in the group with idiopathic hyperprolactinemia and the complaints of these patients and their responses to treatment (medication and/or surgery) were evaluated in detail.
In circulation, prolactin exists in different forms: a monomeric form whose molecular weight (MW) is 22 kDA, a polymeric form, "big prolactin" whose MW is 50-60 kDa, and a larger polymeric form, "macroprolactin," whose MW is greater than 100 kDa.
(4,5) Prolactin can be found in the circulation in one of three isoforms based on its molecular weight: monomeric PRL (small PRL; molecular weight 23 kDa), dimeric PRL (medium PRL; molecular weight 50-60 kDa), and polymeric PRL [large PRL/ macroprolactin (maPRL); molecular weight 150-170 kDa).