Importance of macroprolactinemia in hyperprolactinemia

• Published in: European journal of obstetrics & gynecology and reproductive biology 2014-12, Vol.183, p.28-32
• Main Authors: Kasum, M, Pavičić-Baldani, D, Stanić, P, Orešković, S, Šarić, J-M, Blajić, J, Juras, J
• Format: Article
• Language: English
• Subjects: Adenoma - complications; Antigen-Antibody Complex - blood; Diagnosis; Humans; Hyperprolactinemia; Hyperprolactinemia - blood; Hyperprolactinemia - epidemiology; Hyperprolactinemia - immunology; Macroprolactin; Obstetrics and Gynecology; Pituitary Neoplasms - complications; Prevalence; Prolactin - blood; Treatment
• ISSN: 0301-2115; 1872-7654
• DOI: 10.1016/j.ejogrb.2014.10.013

Abstract Macroprolactin is an antigen–antibody complex of higher molecular mass than prolactin (>150 kDa), consisting of monomeric prolactin and immunoglobulin G. The term ‘macroprolactinemia’ is used when the concentration of macroprolactin exceeds 60% of the total serum prolactin concentration determined by polyethylene glycol precipitation. The gold standard technique for the diagnosis of macroprolactinemia is gel filtration chromatography. The prevalence of macroprolactinemia in hyperprolactinemic populations varies between 15% and 35%. Although the pathogenesis of these antibodies is not clear, it is possible that changes in the pituitary prolactin molecule represent increased antigenicity to the immune system, leading to the production of anti-prolactin antibodies. Mild hyperprolactinemia usually occurs because macroprolactin is not cleared readily from the circulation due to its higher molecular weight. Moreover, the hypothalamic negative feedback mechanism for autoantibody-bound prolactin is inactive because macroprolactin cannot access the hypothalamus, resulting in hyperprolactinemia. Reduced in-vivo bioactivity of macroprolactin may be the reason for the lack of hyperprolactinemic symptoms. It also seems that anti-prolactin autoantibodies may compete with prolactin molecules for receptor binding, resulting in low bioactivity. Additionally, the large molecular size of macroprolactin confined in the intravascular compartment prevents its passage through the capillary endothelium to the target cells, which may be the reason for the lack of symptoms. Macroprolactinemia is considered to be a benign clinical condition in patients with normal concentrations of bioactive monomeric prolactin, with a lack, or low incidence, of hyperprolactinemic symptoms and negative pituitary imaging. In such cases with resistance to anti-prolactinaemic drugs, no pharmacological treatment, diagnostic investigations or prolonged follow-up are required. However, macroprolactinemia may also occur in patients with conventional symptoms of hyperprolactinemia who cannot be differentiated from patients with true hyperprolactinemia. These symptoms are mainly attributed to excess levels of monomeric prolactin, and this is of concern. The diagnosis of macroprolactinemia is misleading and inappropriate. A multitude of physiological, pharmacological and pathological causes, including stress, prolactinomas, hypothyroidism, renal and hepatic failure, intercostal nerve stimulation and