Macroprolactin has reduced bioactivity and accumulates in the sera of some subjects, resulting in apparent hyperprolactinaemia. Development of the polyethyleneglycol (PEG) precipitation technique has enabled large-scale screening for macroprolactin in hyperprolactinaemic subjects. We have reviewed the experience of routine screening for macroprolactin using PEG precipitation over a 54-month period in a single centre.
Plasma levels of prolactin exceeded 500 mU/l in 1903 serum samples (1596 female) from 1350 subjects (1118 female). Application of a reference range for free prolactin (total prolactin - macroprolactin) derived from normal individuals revealed that 415 hyperprolactinaemic samples (22%) were explained by macroprolactinaemia. The percentage of hyperprolactinaemic samples explained by macroprolactinaemia was similar across all levels of total prolactin (17, 21, 19 and 14 percent of samples from 700-1000, 1000-2000, 2000-3000 and greater than 3000 milliunits per litre respectively).
Clinical data was reviewed in a cohort of 182 hyperprolactinaemic patients (144 female) attending Endocrinology clinics, 47 of whom were macroprolactinaemic. Oligomenorrhoea/amenorrhoea and galactorrhoea were more common in female patients with true hyperprolactinemia (p<0.05), but also frequently present in macroprolactinaemic patients. Plasma levels of LH and oestradiol were significantly greater in macroprolactinaemic compared to true hyperprolactinaemic subjects (p<0.05). A revised diagnosis was made and dopamine agonist treatment discontinued in subjects in whom macroprolactinaemia was retrospectively identified following the introduction of screening, while newly presenting macroprolactinaemic subjects did not undergo CT/MRI scanning and were not treated with dopamine agonists.
In summary (i) routine screening for macroprolactin using PEG precipitation revealed that macroprolactinaemia was present in 22% of all hyperprolactinaemic samples, and that the level of total prolactin did not significantly influence this percentage; (ii) macroprolactinaemic patients could not be differentiated from true hyperprolactinaemic patients on the basis of clinical features alone; (iii) following identification of macroprolactin, investigations and treatment were altered in up to 20% of hyperprolactinaemic patients.
22 - 24 Mar 2004
British Endocrine Societies