Macroprolactinaemia in patients with hyperprolactinaemia: composition of macroprolactin and stability during long‐term follow‐up

Abstract

This study showed that higher PEG-precipitable PRL ratio in macroprolactinaemic sera might preferentially indicate the presence of anti-PRL autoantibodies and that macroprolactinaemia might be a long-lasting condition.

Importance of macroprolactinemia in hyperprolactinemia

“…However, further, more comprehensive serial investigations of patients with macroprolactinemia reported a mild symptomatology with a lower incidence of clinical symptoms and abnormal imaging findings in the pituitarry gland than in patients with true hyperprolactinemia [3,5,10,15,[19][20][21][22]. During prolonged follow-up of a cohort of 51 patients with macroprolactinemia headache had been experienced in 12 patients (24%), oligomenorrhea in five (10%) and galactorrhea was present in only two cases (4%) with no symptomatic progression in any of the patients [5].…”

“…However, macroprolactinemia may be more common, with a recently reported prevalence of 3.7% and no difference in prevalence between genders [14]. Because the reported proportion of macroprolactinemia in hyperprolactinemic populations is much higher in most studies and varies between 15 and 35% (mean prevalence 25%), macroprolactinemia is therefore considered a common finding in endocrinological practice [3,8,12,13]. One study reported a prevalence of 46%, but it is likely that this particular incidence reflected selection bias because of the specialized nature of the study center, which received samples sent from other laboratories when the possible diagnosis of macroprolactinemia was raised [15].…”

“…Therefore macroprolactinemia develops due to the delayed clearance of PRL rather than increased production. These PRL autoantibodies are stable with time and long-term follow-up (>10 years) revealed that macroprolactinemia might be a longlasting condition in humans [3,4,19,28]. The second reason for the asymptomatic presentation of macroprolactinemia includes binding of anti-PRL autoantibodies to their binding sites (epitopes) in both N-and C-terminal residues of the PRL molecule which are located near the binding site 1 to PRL receptors.…”

“…In spite of low in vitro bioactivity, the complex apparently lacks in vivo bioactivity although macroprolactin retains its immunoreactivity properties. Owing to its high molecular weight, macroprolactin is confined to the vascular system which may reduce its access to the PRL receptors of target organs in the periphery as well as centrally and it is thus bio-unavailable resulting in asymptomatic hyperprolactinemia [2,3].…”

“…and abnormal imaging changes in the pituitary gland are not common in patients in whom macroprolactin is the predominant form of PRL. These IgG type autoantibodies have a low affinity and high capacity, and long-term follow-up revealed that macroprolactinaemia might be a long-lasting condition [3,4]. In patients with macroprolactinemia and normal concentrations of monomeric PRL there was a low incidence of hyperprolactinemia-related symptoms during prolonged follow-up.…”