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Macroprolactinemia: diagnostic, clinical, and pathogenic significance
Akira Shimatsu1, Naoki Hattori
1Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan. ashimats@kyotolan.hosp.go.jp
Abstract:
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 I125-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.
Insights
Macroprolactinemia, characterized by large prolactin (PRL) complexes, is common in hyperprolactinemia patients. Identifying macroprolactin is crucial for accurate diagnosis, preventing unnecessary treatments.
Area of Science:
- Endocrinology
- Immunology
- Clinical Chemistry
Background:
- Macroprolactinemia involves large prolactin (PRL) complexes, often with IgG and anti-PRL autoantibodies.
- It presents as hyperprolactinemia without typical symptoms and affects 10-25% of hyperprolactinemia patients.
Purpose of the Study:
- To define macroprolactinemia, its characteristics, prevalence, and diagnostic approaches.
- To differentiate macroprolactinemia from other causes of hyperprolactinemia, avoiding unnecessary interventions.
Main Methods:
- Polyethylene-glycol (PEG) precipitation for screening.
- Gel filtration chromatography, protein A/G column, and I125-PRL binding studies for confirmation.
- Analysis of autoantibody epitope and PRL receptor binding site interaction.
Main Results:
- Macroprolactin, a PRL-IgG complex, is the primary form in sera, leading to elevated total PRL levels.
- Macroprolactin exhibits lower biological activity due to autoantibody binding near the PRL receptor site.
- Delayed clearance of autoantibody-bound PRL causes hyperprolactinemia.
Conclusions:
- Macroprolactinemia is a prevalent, chronic condition often developing before middle age.
- Screening for macroprolactinemia is essential for accurate hyperprolactinemia diagnosis.
- Distinguishing macroprolactinemia avoids unnecessary patient examinations and treatments.
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