What labs should be obtained when a patient presents with nipple discharge?

Laboratory Evaluation for Nipple Discharge

The laboratory workup for nipple discharge depends entirely on whether the discharge is physiologic (bilateral, multi-duct, non-spontaneous) or pathologic (unilateral, single-duct, spontaneous, bloody/serous), with labs indicated only for physiologic discharge suggestive of hyperprolactinemia. 1, 2

First Step: Characterize the Discharge

Before ordering any labs, determine the discharge type:

• Physiologic discharge: Bilateral, multiple ducts, white/green/yellow/clear color, requires manipulation to express, no associated mass 2, 3
• Pathologic discharge: Unilateral, single duct, spontaneous, bloody/serous/serosanguineous 2, 3

Laboratory Testing Algorithm

For Physiologic Discharge (Suspected Hyperprolactinemia)

Order these labs in sequence:

1. Serum prolactin level - This is the single most essential test and should be checked first 1

   • Can be drawn at any time of day, does not require fasting 1
   • Use age-specific and sex-specific reference ranges 1
   • If modestly elevated (up to 5× upper limit), repeat on a different day with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related elevation 1

2. Thyroid-stimulating hormone (TSH) - Primary hypothyroidism causes hyperprolactinemia in 40-43% of frank hypothyroidism cases 1

3. Renal function tests (creatinine, BUN) - Chronic kidney disease increases prolactin secretion and reduces renal clearance 1

4. Liver function tests - Severe liver disease is associated with hyperprolactinemia 1

5. Check for macroprolactin - When prolactin is mildly or incidentally elevated, as macroprolactin accounts for 10-40% of hyperprolactinemia cases and is biologically inactive 1

For Pathologic Discharge

No routine laboratory testing is indicated - proceed directly to imaging 4, 2

• Diagnostic mammography/digital breast tomosynthesis (DBT) and ultrasound are the appropriate initial studies, not labs 4, 2
• Cytology of nipple discharge has limited utility and is not routinely recommended 5

Critical Interpretation Points

When Prolactin is Elevated:

• Prolactin >4,000 mU/L (188 μg/L) suggests prolactinoma and warrants pituitary MRI 1
• Large pituitary mass with paradoxically normal/mildly elevated prolactin requires serial dilutions to evaluate for "hook effect" 1

Before Attributing to Prolactinoma:

Conduct thorough medication review - dopamine antagonists (antipsychotics, antiemetics, certain antidepressants) are among the most common causes of hyperprolactinemia 1

Common Pitfalls to Avoid

• Do not order prolactin for pathologic (bloody/serous, unilateral, single-duct) discharge - this requires imaging, not labs 4, 2
• Do not rely on single mildly elevated prolactin - stress-related elevation is common and requires confirmation 1
• Do not skip TSH testing - hypothyroidism is a frequent reversible cause of hyperprolactinemia 1
• Do not miss macroprolactin - this benign condition mimics true hyperprolactinemia and leads to unnecessary treatment if not identified 1
• Do not order ductography, cytology, or other labs routinely - these have little role when imaging is negative 5

When Labs Are Complete

• If all labs normal with physiologic discharge: No imaging needed, reassure patient and advise to stop breast manipulation 2, 3
• If hyperprolactinemia confirmed after excluding medications/hypothyroidism/renal/hepatic disease: Proceed to pituitary MRI 1
• If pathologic discharge: Skip labs entirely and proceed directly to age-appropriate imaging (mammography/DBT + ultrasound for age ≥40 years or ≥30 years; ultrasound alone for <30 years) 4, 2