The impact on clinical practice of routine screening for macroprolactin.
BACKGROUND
Macroprolactin has reduced bioactivity in vivo and accumulates in the sera of some subjects, resulting in pseudo-hyperprolactinemia and consequent misdiagnosis.


METHODS
We have audited our experience of routine screening for macroprolactin using polyethylene glycol (PEG) precipitation over a 5-yr period in a single center.


RESULTS
Application of a reference range for monomeric prolactin (the residual prolactin present in macroprolactin-depleted serum) for normal individuals revealed that 453 of 2089 hyperprolactinemic samples (22%) identified by Delfia immunoassay were explained entirely by macroprolactin. The percentage of hyperprolactinemic samples explained by macroprolactinemia was similar across all levels of total prolactin (18, 21, 19, and 17% of samples from 700-1000, 1000-2000, 2000-3000, and greater than 3000 mU/liter, respectively). Application of an absolute prolactin threshold after polyethylene glycol treatment of sera, rather than the traditional method, i.e. less than 40% recovery, minimizes the opportunity for misclassification of patients in whom macroprolactin accounted for more than 60% of prolactin and the residual bioactive prolactin was present in excess. Macroprolactinemic patients could not be differentiated from true hyperprolactinemic patients on the basis of clinical features alone. Although oligomenorrhea/amenorrhea and galactorrhea were more common in patients with true hyperprolactinemia (P < 0.05), they were also frequently present in macroprolactinemic patients. Plasma levels of estradiol and LH and the LH/FSH ratio were significantly greater in macroprolactinemic compared with true hyperprolactinemic subjects (P < 0.05). Reduced use of imaging and dopamine agonist treatment resulted in a net cost savings, offsetting the additional cost associated with the introduction of screening.


CONCLUSIONS
Routine screening of all hyperprolactinemic sera for macroprolactin is recommended.
Gibney
J
J
Department of Endocrinology and Diabetes Mellitus, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Smith
T P
TP
McKenna
T J
TJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D011388:Prolactin / Q000097:blood*; D012189:Retrospective Studies
C060678:prolactin, polymeric; D011388:Prolactin; D007986:Luteinizing Hormone