Macroprolactinemia is characterized by a large molecular mass of PRL (macroprolactin) as the main molecular form of PRL in sera, the frequent elevation of serum PRL (hyperprolactinemia), and the lack of symptoms. Macroprolactin is largely a complex of PRL with immunoglobulin G (IgG), especially anti-PRL autoantibodies. The prevalence of macroprolactinemia is 10–25% in patients with hyperprolactinemia and 3.7% in general population. There is no gender difference and a long-term followup demonstrates that macroprolactinemia develops before middle age and is likely a chronic condition. Polyethylene-glycol- (PEG-) precipitation method is widely used for screening macroprolactinemia, and gel filtration chromatography, protein A/G column, and -PRL binding studies are performed to confirm and clarify its nature. The cross-reactivity of macroprolactin varies widely according to the immunoassay systems. The epitope on PRL molecule recognized by the autoantibodies is located close to the binding site for PRL receptors, which may explain that macroprolactin has a lower biological activity. Hyperprolactinemia frequently seen in macroprolactinemic patients is due to the delayed clearance of autoantibody-bound PRL. When rats are immunized with rat pituitary PRL, anti-PRL autoantibodies are produced and hyperprolactinemia develops, mimicking macroprolactinemia in humans. Screening of macroprolactinemia is important for the differential diagnosis of hyperprolactinemia to avoid unnecessary examinations and treatments. 1. Introduction Prolactin (PRL) is an anterior pituitary hormone that plays an important role in lactation during pregnancy but has many other biological functions such as osmoregulation, angiogenesis, and immunoregulation [1]. PRL facilitates the maturation of T cells via IL-2 receptor expression, impairs B cell tolerance to self-antigens through the anti-apoptotic effect, develops antigen-presenting cells, and enhances immunoglobulin production [2]. The increase in serum PRL concentrations (hyperprolactinemia) often develops symptoms such as amenorrhea and galactorrhea in women and impotence in men. It is caused physiologically by pregnancy and pathologically by PRL secreting pituitary adenoma (prolactinoma), hypothalamic and pituitary diseases compressing pituitary stalk, antidopaminergic drugs, hypothyroidism, chest wall diseases, and hepatorenal disorders [3]. However, 29% of hyperprolactinemia has been classified as “idiopathic” because the causes are unknown [4]. Microadenomas in the pituitary gland that cannot be detected by computed tomography
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