Defining Elevated Prolactin Levels
Prolactin levels above 20 μg/L (or 20 ng/ml) are considered elevated in both men and women. 1, 2, 3
Normal Ranges and Diagnostic Thresholds
- Prolactin levels vary with age and sex, being higher in the first 2 years of life, decreasing in mid-childhood, and increasing again in adolescence, with higher levels in girls than boys 2
- The mean serum prolactin level in normal premenopausal women is approximately 10.6 ± 3.0 ng/ml, which differs from postmenopausal women (8.2 ± 4.0 ng/ml) and women taking combined oral contraceptives (12.2 ± 4.0 ng/ml) 3
- Stress can elevate prolactin levels up to five times the upper limit of normal, which is why serial measurements taken 20-60 minutes apart using an indwelling cannula may be helpful to differentiate stress-related elevation from organic disease 2, 4
Clinical Significance of Different Prolactin Levels
Mild Elevation (20-100 μg/L)
- Mild elevations (20-100 μg/L) can be caused by medications, stress, hypothyroidism, or non-prolactin secreting pituitary lesions 2, 5
- In patients with non-functioning pituitary adenomas, 73.2% of those with hyperprolactinemia had prolactin levels <1000 mIU/l (approximately 47 ng/ml) 6
Moderate Elevation (100-250 μg/L)
- Prolactin values between 100-1000 μg/L strongly suggest a prolactin-producing tumor 5
- In patients with expansively growing pituitary adenomas, prolactin levels may range from 15 to 100 μg/L 5
Significant Elevation (>250 μg/L)
- Prolactin levels exceeding 4,000 mU/l (approximately 188 μg/L) in children and adolescents generally indicate prolactinomas 2
- In patients with invasively growing pituitary adenomas, prolactin levels can be very high, ranging from 1,230 to 31,500 μg/L 5
- Serum prolactin values >1000 μg/L in a patient with sellar destruction is strong evidence of an invasive pituitary adenoma 5
Diagnostic Considerations
- The Endocrine Society recommends confirming hyperprolactinemia with a single blood sample collected at any time of day 4
- For patients with modestly elevated prolactin levels, consider serial measurements to rule out stress-related elevation 4
- When evaluating hyperprolactinemia, it's essential to exclude other causes such as hypothyroidism, renal or hepatic insufficiency, and medication effects 2, 4
- Serum luteinizing hormone levels should be measured in patients with low testosterone and low or low/normal LH levels to help establish the etiology of hyperprolactinemia 1
Clinical Implications
- Hyperprolactinemia can lead to menstrual disturbances, galactorrhea, and subfertility in women, and decreased libido, erectile dysfunction, and gynecomastia in men 2
- Persistently elevated prolactin levels can indicate the presence of pituitary tumors, such as prolactinomas, and such patients should be referred to an endocrinologist for further evaluation 1
- Men with total testosterone levels <150 ng/dL in combination with low or low/normal LH should undergo pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be present 1
Common Pitfalls and Caveats
- Physiologic hyperprolactinemia can occur after sexual activities, exercise, lactation, during pregnancy, and after stressful venipuncture 7
- Macroprolactinemia (presence of high molecular weight prolactin with reduced bioactivity) should be considered in cases of asymptomatic hyperprolactinemia 2
- In patients with large pituitary lesions and normal or slightly elevated prolactin levels, serial serum dilutions for prolactin measurement should be performed to avoid the "hook effect" that can lead to falsely low prolactin readings 2
- Moderately raised serum prolactin values (up to 100 μg/L) in a patient with a sellar tumor does not definitively prove that the tumor is a prolactinoma 5