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Macroprolactinaemia, the major unknown in the differential diagnosis of hyperprolactinaemia
F Cattaneo1, D Kappeler, B Müller
1Department of Endocrinology and Diabetology, University of Berne, Inselspital, Berne, Switzerland. fabiocattaneo@email.com
Abstract:
We report on 10 cases of macroprolactinaemia and discuss recent evidence that many patients with hyperprolactinaemia (8-26%, depending on the population studied) have in fact normal amounts of circulating prolactin but false-high values in commercial assays. This is caused by macromolecular prolactin (also named big-big prolactin or macroprolactin), a complex of prolactin with IgG antibodies leading to apparent hyperprolactinaemia. In spite of the expanding literature on this topic, it remains an underrecognised problem, typically causing unnecessary procedures such as laboratory controls, MRI of the pituitary, treatment with dopamine agonists or even pituitary surgery. Physicians involved with diagnosis and treatment of hyperprolactinaemia (general practitioners, gynaecologists, neurosurgeons, endocrinologists and biochemists) should suspect the presence of apparent hyperprolactinaemia in any patient with a high prolactin value but no related symptoms. Medical laboratories should be aware that their prolactin assay can interfere with macroprolactin and should implement the use of the PEG precipitation test in the work-up of hyperprolactinaemia, a simple and effective means of correctly diagnosing apparent hyperprolactinaemia.
Insights
Many hyperprolactinaemia cases are false-high due to macroprolactin, a prolactin-antibody complex. This underrecognized issue causes unnecessary tests and treatments, highlighting the need for accurate diagnosis.
Area of Science:
- Endocrinology
- Clinical Chemistry
- Immunology
Background:
- Hyperprolactinaemia is commonly diagnosed using commercial assays.
- A significant percentage of patients with apparent hyperprolactinaemia may have normal circulating prolactin levels.
- Macroprolactin, a complex of prolactin with IgG antibodies, causes falsely elevated prolactin measurements.
Purpose of the Study:
- To report cases of macroprolactinaemia.
- To discuss the prevalence and implications of macroprolactinaemia.
- To emphasize the need for improved diagnostic strategies for hyperprolactinaemia.
Main Methods:
- Review of 10 cases of macroprolactinaemia.
- Discussion of existing literature on macroprolactin and its detection.
- Highlighting the utility of the PEG precipitation test.
Main Results:
- Macroprolactinaemia is an underrecognized cause of apparent hyperprolactinaemia.
- False-high prolactin values can lead to unnecessary investigations like pituitary MRI and treatments.
- The PEG precipitation test is effective in diagnosing macroprolactinaemia.
Conclusions:
- Physicians should suspect macroprolactinaemia in asymptomatic patients with elevated prolactin.
- Laboratories should implement the PEG precipitation test to differentiate true from apparent hyperprolactinaemia.
- Accurate diagnosis of macroprolactinaemia avoids unnecessary medical interventions.