The use of the domperidone test in differentiating macroprolactinaemia from true hyperprolactinaemia
L Pinto, M Evans, F Hanna & M Scanlon
Macroprolactin is a complex of prolactin with immunoglobulin appearing to have limited biological activity, partly due to failure of this high-molecular weight complex to cross capillary walls.
Macroprolactinaemia is a common phenomenon, it is thus important to identify this condition in order to avoid unnecessary investigations and treatment. Although the presence of macroprolactin can be confirmed by gel filtration chromatography, this is time consuming and expensive; and there are no clinical features which reliably distinguish this condition from true hyperprolactinaemia.
Previous studies in hyperprolactinaemic subjects have shown exaggerated TSH responses to DA2 receptor antagonism with domperidone reflecting positive feedback of hyperprolactinaemia on hypothalamic dopaminergic receptors.
We thus investigated the hypothesis that subjects with macroprolactinaemia, with reduced biological activity, should have normal dopaminergic function with normal TSH responses to DA antagonism.
We therefore studied TSH & PRL responses in 12 subjects with macroprolactinaemia and in an equal number of age-matched patients with hyperprolactinaemia secondary to microprolactinoma.
In patients with macroprolactinaemia, the mean TSH rise at 30 min following 10 mg of IV domperidone was 0.9 mu/l ( range: 0.03 to 2.29); compared to a mean TSH rise of 7.5 mu/l ( range: 3.36 to 21.3) in patients with microprolactinoma. The difference in the TSH response between the 2 groups being highly significant at p < 0.001.
These data thus support the hypothesis of reduced biological activity of macroprolactin. This simple investigation may be used in clinical practice to distinguish between true hyperprolactinaemia and macroprolactinaemia.