What is the workup for an 18-year-old with mildly elevated prolactin (hyperprolactinemia)?

Workup for Prolactin Level 14.9 in an 18-Year-Old

For an 18-year-old with a prolactin level of 14.9 (assuming units are ng/mL or μg/L), this falls within or just below the normal range for adults (<20 μg/L), and therefore does not require further workup unless the patient is symptomatic. 1, 2

Initial Assessment

Confirm the Prolactin Level is Actually Elevated

• Normal prolactin levels are typically <20 μg/L (<425 mU/L) for non-pregnant adults, with women having slightly higher baseline levels than men. 3, 2
• A level of 14.9 μg/L is not elevated and falls within normal reference ranges. 2
• If this value is in different units (e.g., ng/dL), convert to standard units before proceeding. 1

If Prolactin is Truly Elevated (>20 μg/L)

Confirm hyperprolactinemia with a single blood sample collected at any time of day, as timing is not critical for diagnosis. 1 However, for modestly elevated levels, consider serial measurements taken 20-60 minutes apart using an indwelling cannula to differentiate stress-related elevation from organic disease, as stress can elevate prolactin up to five times the upper limit of normal. 1, 3

Exclude Secondary Causes

Before pursuing imaging or treatment, systematically exclude the following:

Medications

• Review all medications that antagonize dopamine or directly stimulate prolactin secretion, including antipsychotics (especially typical antipsychotics), antidepressants, antihypertensives, and prokinetic agents. 3, 4
• Medications are one of the most common causes of hyperprolactinemia. 3

Hypothyroidism

• Measure TSH and free T4 to exclude primary hypothyroidism, which causes hyperprolactinemia in 43% of women and 40% of men with primary hypothyroidism through compensatory hypersecretion of thyrotropin-releasing hormone. 1, 3
• Hypothyroidism must be excluded before confirming the diagnosis. 1

Renal and Hepatic Function

• Check renal function (creatinine, eGFR), as chronic kidney disease causes hyperprolactinemia in 30-65% of adult patients due to increased secretion and reduced renal clearance. 3
• Assess liver function, as severe liver disease is associated with hyperprolactinemia. 3

Macroprolactinemia

• Screen for macroprolactinemia in cases of mild or incidental elevation, as 10-40% of hyperprolactinemia in adults is due to macroprolactin, which is biologically inactive. 1, 3

Imaging Considerations

When to Order MRI

• MRI of the pituitary should be performed when prolactin levels are significantly elevated, typically >4,000 mU/L (>188 μg/L) in pediatric populations, as these levels generally indicate prolactinomas. 1, 3
• For patients with visual symptoms or signs of mass effect, perform MRI regardless of prolactin level. 1
• The American College of Radiology recommends MRI for unexplained hyperprolactinemia even with mild elevations, as pituitary adenomas can present with only modestly elevated prolactin levels. 1

Special Consideration: High-Dose Hook Effect

• For patients with large pituitary lesions but paradoxically normal or mildly elevated prolactin, perform serial dilutions to detect the "high-dose hook effect", which causes falsely low measurements in approximately 5% of macroprolactinomas. 1, 3, 2

Additional Hormonal Assessment

• Measure luteinizing hormone (LH) levels to help establish the etiology of hyperprolactinemia, particularly in patients with hypogonadism. 1, 3
• Assess for clinical signs of hypogonadism: in women, look for amenorrhea/oligomenorrhea, anovulation, and galactorrhea; in men, assess for decreased libido, erectile dysfunction, and gynecomastia. 3, 2

Clinical Pitfalls to Avoid

• Do not pursue extensive workup for prolactin levels within normal range unless the patient has clear symptoms of hyperprolactinemia or pituitary mass effect. 1, 2
• Do not assume all elevated prolactin requires imaging—first exclude medications, hypothyroidism, and physiologic causes. 1, 3
• Do not miss stalk compression from non-prolactin-secreting tumors, which can cause mild-to-moderate prolactin elevation by interrupting dopaminergic inhibition. 3
• In adolescents, remember that prolactin levels are higher than in mid-childhood and vary by sex, with girls having higher levels than boys. 1, 3