When should prolactin levels be measured in patients suspected of having a pituitary adenoma?

When to Measure Prolactin for Pituitary Adenoma

Prolactin levels should be measured in patients presenting with delayed puberty, galactorrhea, visual field loss, growth or pubertal arrest, menstrual disturbances, infertility, or symptoms of hypogonadism to screen for pituitary adenoma. 1, 2, 3

Indications for Prolactin Measurement

• Measure prolactin in patients presenting with one or more of the following clinical features:
  • Delayed or arrested puberty 1, 2
  • Galactorrhea 1, 2
  • Visual field defects or loss 1, 2
  • Growth failure or short stature 1
  • Primary amenorrhea or menstrual disturbances in females 1, 2
  • Secondary amenorrhea in post-menarcheal girls 1
  • Infertility 2
  • Gynaecomastia in males 1, 2
  • Symptoms of hypogonadism (decreased libido, erectile dysfunction) 2, 4
  • Headaches with other suspicious symptoms 1

Proper Sampling Technique

• A single prolactin measurement taken at any time of the day is sufficient to assess hyperprolactinemia 1, 3
• For modestly elevated prolactin levels (up to five times the upper limit of normal), consider:
  • Repeat sampling on a different day to exclude stress-induced elevation 1, 2
  • Serial measurements taken 20-60 minutes apart using an indwelling cannula to differentiate stress-related hyperprolactinemia from organic disease 2, 3
• Morning fasting samples are preferred for repeat measurements 2
• Use age-specific and sex-specific reference ranges, as prolactin levels vary with age and sex 3

Additional Testing When Hyperprolactinemia Is Confirmed

• Measure luteinizing hormone (LH) levels in all patients with confirmed hyperprolactinemia 2, 3
• Screen for secondary causes:
  • Review medications that can cause hyperprolactinemia (particularly antipsychotics and dopamine antagonists) 2, 3
  • Test for pregnancy, primary hypothyroidism, liver disease, and renal failure 2, 3, 4
• Consider macroprolactinemia in patients with mildly elevated prolactin levels who are asymptomatic 2, 3
• For patients with large pituitary lesions but only modestly elevated prolactin levels, perform serum dilutions to rule out the "hook effect" (falsely low prolactin readings due to assay saturation) 2, 3
• Consider measuring IGF-1 levels to rule out mixed prolactin and growth hormone hypersecretion 2

Correlation Between Prolactin Levels and Tumor Type

• Prolactin levels typically correlate with tumor type and size:
  • Levels >4,000 mU/L (188 μg/L) in pediatric populations strongly suggest a prolactinoma 3, 4
  • Levels >100 μg/L strongly indicate a prolactin-producing tumor 5
  • Levels >1,000 μg/L in a patient with sellar destruction are diagnostic of an invasive pituitary adenoma 5
  • Modest elevations (15-100 μg/L) can be seen in both prolactinomas and non-functioning pituitary adenomas causing stalk compression 5, 6

When to Perform Pituitary Imaging

• Obtain pituitary MRI when:
  • Prolactin levels are significantly elevated, suggesting a prolactinoma 2, 3
  • Visual symptoms or signs of mass effect are present, regardless of prolactin level 3
  • Men have total testosterone levels <150 ng/dL combined with low/low-normal LH 2, 3

Pitfalls to Avoid

• Don't miss the "hook effect" - falsely low prolactin levels in large tumors due to assay saturation 2, 3
• Don't overlook macroprolactinemia - present in 10-40% of patients with hyperprolactinemia and may not require treatment 2
• Don't rely solely on prolactin levels for monitoring patients with known or suspected MEN1 syndrome - periodic MRI scans are necessary even with borderline elevated prolactin levels 7
• Don't assume that modestly elevated prolactin levels (up to 100 μg/L) in a patient with a sellar tumor definitively prove the tumor is a prolactinoma 5
• Don't forget that not all large non-functioning pituitary adenomas cause hyperprolactinemia - tumor growth pattern (width/anteroposterior diameter ratio) may be more important than tumor volume 6

When to Refer to an Endocrinologist

• Persistently elevated prolactin levels after excluding common causes 2
• Men with total testosterone <150 ng/dL and low/low-normal LH 2
• Patients with confirmed pituitary adenomas 1, 2