What is the workup for a patient presenting with galactorrhea?

Workup for Galactorrhea

All patients presenting with galactorrhea require serum prolactin measurement as the essential first step, followed by thyroid function tests and pregnancy testing, with pituitary MRI reserved for significantly elevated prolactin levels or concerning clinical features. 1, 2, 3

Initial Laboratory Evaluation

Mandatory First-Line Tests

• Serum prolactin level is essential for all patients with galactorrhea, regardless of other symptoms, and can be collected at any time of day as timing is not critical for diagnosis 1, 2
• Pregnancy test must be performed to exclude physiologic hyperprolactinemia 2, 4, 5
• Thyroid-stimulating hormone (TSH) should be measured to exclude hypothyroidism, which can cause galactorrhea even with normal prolactin levels 1, 3, 6
• Renal function tests to assess for chronic kidney disease as a secondary cause 1, 5

Interpretation of Prolactin Results

• For mildly elevated prolactin, consider serial measurements taken 20-60 minutes apart using an indwelling cannula to differentiate stress-related elevation from organic disease 1, 2
• Macroprolactin assessment should be considered if prolactin is elevated but clinical features are inconsistent, as 10-40% of hyperprolactinemia in adults is due to macroprolactin 1, 2, 3
• For patients with large pituitary lesions but paradoxically normal or mildly elevated prolactin, perform serial dilutions to detect the "high-dose hook effect" which can cause falsely low results 1, 2, 3

Additional Hormonal Testing

• FSH and LH should be measured if amenorrhea is present to help establish the etiology of hyperprolactinemia 1, 2

Imaging Studies

Indications for Pituitary MRI

• High-resolution pituitary MRI (the gold standard) is indicated when: 1, 2, 3
  • Prolactin levels are significantly elevated (typically >4,000 mU/L or 188 μg/L)
  • Visual symptoms or signs of mass effect are present, regardless of prolactin level
  • No other cause of hyperprolactinemia is identified after excluding medication effects, hypothyroidism, and renal impairment
• MRI is recommended even for mild prolactin elevations if unexplained, as pituitary adenomas can present with only modestly elevated levels and early detection impacts treatment outcomes 2

History and Physical Examination

Key Historical Elements to Assess

• Medication review is crucial, as many drugs cause hyperprolactinemia through direct prolactin stimulation or dopamine antagonism (antipsychotics, metoclopramide, domperidone, H2-blockers) 1, 3, 6
• Menstrual history including presence of amenorrhea or oligomenorrhea 1, 4, 5
• Fertility concerns and contraceptive use 4, 5
• Symptoms of hypothyroidism (fatigue, weight gain, cold intolerance) 1, 6
• Visual symptoms suggesting mass effect 2
• Breast stimulation or chest wall irritation history 5

Physical Examination Focus

• Assess for signs of hypothyroidism (bradycardia, delayed reflexes, dry skin) 1
• Evaluate for hirsutism and other signs of androgen excess 1
• Visual field testing if macroprolactinoma suspected 2, 5
• Confirm galactorrhea and assess bilateral versus unilateral presentation 4, 5

Common Pitfalls to Avoid

• Failing to check prolactin levels in patients with galactorrhea, even when there are no other symptoms, is a critical error 1, 3
• Not performing dilutions when measuring prolactin in patients with large pituitary lesions leads to missed diagnoses due to the hook effect 1, 3
• Neglecting macroprolactin assessment can result in unnecessary treatment for laboratory hyperprolactinemia without true clinical disease 1, 3
• Ordering MRI prematurely before confirming hyperprolactinemia with laboratory testing and excluding secondary causes 2
• Not recognizing that galactorrhea can occur with normal prolactin levels, particularly in hypothyroidism or medication-induced cases 6

Clinical Context

The workup should be systematic and cost-effective. Most galactorrhea after infancy is medication-induced, with pituitary tumors being the most common pathologic cause 4. The natural history of hyperprolactinemia is generally benign, with many microadenomas remaining stable or regressing over time 7. This supports a measured diagnostic approach that prioritizes laboratory evaluation before advanced imaging, except when clinical features suggest mass effect or significantly elevated prolactin levels warrant immediate structural assessment 2, 7.