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Submitted on November 12, 2004
Accepted on March 25, 2005
Department of Endocrinology and Diabetes Mellitus, St. Vincent's University Hospital, Elm Park and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland
* To whom correspondence should be addressed. E-mail: tjmckenna{at}ucd.ie.
Macroprolactin has reduced bioactivity in vivo and accumulates in the sera of some subjects resulting in pseudo-hyperprolactinemia and consequent misdiagnosis. We have audited our experience of routine screening for macroprolactin using PEG precipitation over a 5-year period in a single center.
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 3000mU/L respectively). Application of an absolute PRL threshold following PEG treatment of sera, rather than the traditional method, i.e. < 40% recovery, minimizes the opportunity for misclassification of patients where macroprolactin accounted for > 60% of PRL 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. While 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 prescription resulted in a net cost saving offsetting the additional cost associated with the introduction of screening. Routine screening of all hyperprolactinemic sera for macroprolactin is recommended.
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