Abstract
Hypersecretion of prolactin by lactotroph cells of the anterior pituitary may lead to hyperprolactinemia in physiological, pathological and idiopathic conditions. Most patients with idiopathic hyperprolactinemia may have radiologically undetected microprolactinomas, but some may present other causes of hyperprolactinemia described as macroprolactinemia. This condition corresponds to the predominance of higher molecular mass prolactin forms (big-big prolactin, MW > 150 kDa), that have been postulated to represent prolactin monomer complexed with anti-prolactin immunoglobulins or autoantibodies. The prevalence of macroprolactinemia in hyperprolactinemic populations between 15-46% has been reported. In the pathophysiology of macroprolactinemia it seems that pituitary prolactin has antigenicity, leading to the production of anti-prolactin autoantibodies, and these antibodies reduce prolactin bioactivity and delay prolactin clearance. Antibody-bound prolactin is big enough to be confined to vascular spaces, and therefore macroprolactinemia develops due to the delayed clearance of prolactin rather than increased production. Although the clinical symptoms are less frequent in macroprolactinemic patients, they could not be differentiated from true hyperprolactinemic patients, on the basis of clinical features alone. Although gel filtration chromatography (GFC) is known to be the gold standard for detecting macroprolactin, the polyethylene glycol precipitation (PEG) method has offered a simple, cheap, and highly suitable alternative. In conclusion, macroprolactinemia can be considered a benign condition with low incidence of clinical symptoms and therefore hormonal and imaging investigations as well as medical or surgical treatment and prolonged follow-up are not necessary.
Highlights
Human prolactin (PRL) is a single polypeptide hormone containing 198 amino acid residues identified in 1970
The knowledge of the ways to diagnose and interpret macroprolactinemia means benefit for the patient safety
All the patients with hyperprolactinenia radiographic data incompatible with their PRL levels with no regard to clinical symptoms should be routinely screened for the presence of macroprolactin to avoid unnecessary investigations, incorrect diagnosis and inappropriate dopamine agonist treatment
Summary
Human prolactin (PRL) is a single polypeptide hormone containing 198 amino acid residues identified in 1970. Macroprolactinemia is heterogeneous the condition is characterized by the predominance of circulating high molecular mass PRL forms which have coupled with anti-PRL immunoglobulins These autoantibodies have been found to be immunoglobulin (IgG) isotypes with low receptor affinity in vivo and they may be a primary cause of hyperprolactinemia. Suliman et al argue that the symptoms and hyperprolactinemia attributable to macroprolactin in these cases are coincidental, whereas Olukoga suggests that the macroprolactin complex may dissociate in vivo in some cases, releasing bioactive, monomeric PRL that causes the symptoms [16,26] It is, possible that increasing bioavailability of monomeric PRL due, perhaps, to intermittent dissociation from the low affinity, high capacity IgG antibody to which it is bound in macroprolactin, and/ or influence of macroprolactin in PRL secretion, may be a contributory factor to development of symptoms of PRL excess
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