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The impact on clinical practice of routine screening for macroprolactin
J Gibney1, T P Smith, T J McKenna
1Department of Endocrinology and Diabetes Mellitus, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
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.
Conclusion:
Routine screening of all hyperprolactinemic sera for macroprolactin is recommended.
Insights
Routine screening for macroprolactin in hyperprolactinemic sera is recommended. This approach accurately identifies cases caused by macroprolactin, preventing misdiagnosis and unnecessary treatments.
Area of Science:
- Endocrinology
- Clinical Chemistry
- Laboratory Medicine
Background:
- Macroprolactin, a less bioactive form of prolactin, can accumulate in serum.
- This accumulation leads to pseudo-hyperprolactinemia, increasing the risk of misdiagnosis.
Purpose of the Study:
- To evaluate the utility of routine macroprolactin screening using polyethylene glycol (PEG) precipitation.
- To assess the impact of macroprolactin on hyperprolactinemia diagnosis and patient management.
Main Methods:
- A 5-year audit of routine macroprolactin screening using PEG precipitation in a single center.
- Analysis of hyperprolactinemic samples to determine the proportion explained by macroprolactin.
- Comparison of clinical features and biochemical markers between macroprolactinemic and true hyperprolactinemic patients.
Main Results:
- Macroprolactin explained 22% of hyperprolactinemic samples (453/2089).
- The prevalence of macroprolactinemia was consistent across different total prolactin levels.
- A modified threshold after PEG treatment minimized misclassification.
- Clinical features alone could not reliably differentiate macroprolactinemic from true hyperprolactinemic patients.
- Macroprolactinemic patients showed significantly higher estradiol, LH, and LH/FSH ratios.
- Screening led to cost savings by reducing imaging and unnecessary treatments.
Conclusions:
- Routine screening for macroprolactin in all hyperprolactinemic sera is recommended.
- This screening improves diagnostic accuracy and optimizes patient management.
- Macroprolactin screening is cost-effective.
