Laboratory Evaluation for Nipple Discharge Related to Pituitary Gland
Check a serum prolactin level as the first and most essential laboratory test when nipple discharge is suspected to be pituitary-related. 1, 2
Initial Laboratory Testing
Measure serum prolactin in a single blood sample collected at any time of day - this is sufficient for initial assessment and does not require fasting or specific timing 1, 2
Use age-specific and sex-specific reference ranges when interpreting prolactin levels, as values vary significantly with age and sex 1
Obtain a pregnancy test in all premenopausal women presenting with nipple discharge before proceeding with further evaluation 3
Additional Essential Laboratory Tests
After measuring prolactin, the following tests should be obtained to exclude common secondary causes of hyperprolactinemia:
Thyroid-stimulating hormone (TSH) - primary hypothyroidism is a common cause of hyperprolactinemia, occurring in 40-43% of patients with frank hypothyroidism 2, 3
Renal function tests (creatinine, BUN) - chronic kidney disease causes hyperprolactinemia through increased prolactin secretion and reduced renal clearance 1, 3
Liver function tests - severe liver disease is associated with hyperprolactinemia in adults 1
Interpreting Prolactin Levels
Prolactin levels directly correlate with tumor size: diagnostic serum prolactin concentrations in prolactinomas are usually above 4,000 mU/L (188 μg/L), though lower levels can occur with microprolactinomas 1
For modestly elevated prolactin (up to 5 times the upper limit of normal), consider serial measurements on a different day using an indwelling cannula with 2-3 samples at 20-60 minute intervals to exclude stress-related elevation 1, 2
Critical Laboratory Considerations
Macroprolactin Assessment
Check for macroprolactin when prolactin is mildly or incidentally elevated - macroprolactin (biologically inactive prolactin-antibody complexes) accounts for 10-40% of hyperprolactinemia cases in adults and can lead to unnecessary investigations 1, 2
Request polyethylene glycol (PEG) precipitation to distinguish monomeric prolactin from macroprolactin 4
Hook Effect Evaluation
Perform serial dilutions of serum for prolactin measurement when there is a large pituitary lesion but paradoxically normal or mildly elevated prolactin - the "hook effect" occurs in approximately 5% of macroprolactinomas where extremely high prolactin concentrations saturate the immunoassay, producing falsely low measurements 1, 2
Contact the clinical biochemist to request manual dilution when imaging shows a large adenoma but prolactin seems disproportionately low 1
Medication Review
Conduct a thorough medication review before attributing hyperprolactinemia to a pituitary adenoma - medications (particularly dopamine antagonists like antipsychotics, antiemetics, and certain antidepressants) are among the most common causes of hyperprolactinemia 1, 2, 3
Discontinue offending medications if clinically feasible before proceeding with imaging 3
When to Proceed to Imaging
Order pituitary MRI if hyperprolactinemia persists after excluding medication effects, hypothyroidism, renal disease, and liver disease 2, 3
MRI is indicated when prolactin levels suggest a prolactinoma (typically >4,000 mU/L or 188 μg/L) or when the cause of hyperprolactinemia remains unclear after laboratory evaluation 1, 2
Common Pitfalls to Avoid
Do not assume all elevated prolactin represents a prolactinoma - always exclude physiologic causes (pregnancy), medications, hypothyroidism, and renal/hepatic disease first 1, 3
Do not rely on a single mildly elevated prolactin value - stress-related elevation is common and requires confirmation with repeat testing 1, 2
Do not miss the hook effect - always request serial dilutions when imaging shows a large pituitary mass but prolactin is only modestly elevated 1, 2
Do not overlook macroprolactin - this benign condition can mimic true hyperprolactinemia and lead to unnecessary treatment if not identified 1, 2, 4