Initial Approach to Hyperprolactinemia
The initial approach to a patient with hyperprolactinemia should include measuring serum luteinizing hormone levels, ruling out medication effects, assessing for secondary causes, and considering pituitary imaging, with dopamine agonist therapy as first-line treatment for confirmed prolactinomas. 1
Diagnostic Evaluation
Initial Assessment
- Confirm hyperprolactinemia with a repeat measurement, preferably in the morning while fasting, to exclude stress-induced or pulsatile elevation 1
- For modestly elevated prolactin levels (up to five times the upper limit of normal), consider serial measurements with samples taken 20-60 minutes apart using an indwelling cannula to differentiate stress-related hyperprolactinemia from organic disease 1
- Assess for clinical symptoms such as:
- Delayed or arrested puberty
- Galactorrhea
- Visual field disturbances
- Menstrual irregularities or amenorrhea
- Infertility
- Hypogonadism 1
Rule Out Secondary Causes
- Review medications that can cause hyperprolactinemia (particularly antipsychotics and other dopamine antagonists) 1
- Screen for:
- Pregnancy (in women of reproductive age)
- Primary hypothyroidism (measure TSH)
- Renal failure
- Liver disease
- Intracranial hypotension 1
Laboratory Testing
- Measure luteinizing hormone (LH) levels in all patients with confirmed hyperprolactinemia 1
- Assess for macroprolactinemia in patients with mildly or incidentally elevated prolactin levels, especially if asymptomatic 1
- Consider serum dilutions for prolactin measurement in patients with large pituitary lesions but only modestly elevated prolactin levels to rule out the "hook effect" (falsely low values due to assay saturation) 1
- Measure estradiol in male patients with breast symptoms or gynecomastia 1
- Evaluate IGF-1 levels to rule out mixed prolactin and growth hormone hypersecretion 1
Imaging
- Obtain pituitary MRI when:
Treatment Approach
First-Line Therapy
- Dopamine agonists are the first-line treatment for prolactinomas to reduce serum prolactin and induce tumor shrinkage 1
- Cabergoline is preferred over bromocriptine due to superior effectiveness and better tolerability 1, 2
- Bromocriptine remains the treatment of choice for women planning pregnancy due to more extensive safety data during pregnancy 3
Monitoring
- Monitor prolactin levels to assess treatment response 1
- For patients on cabergoline, perform echocardiographic monitoring every 6-12 months to assess for cardiac valvulopathy, particularly at higher doses 4
- Watch for signs of fibrotic complications (pleural, pericardial, retroperitoneal) in patients on long-term dopamine agonist therapy 4, 5
Special Considerations
Pitfalls to Avoid
- Do not miss the "hook effect" - falsely low prolactin levels in large tumors due to assay saturation. Always consider serial dilutions when a large pituitary mass is present with only modestly elevated prolactin 1, 6
- Do not overlook macroprolactinemia - present in 10-40% of patients with hyperprolactinemia and may not require treatment 1
- Do not immediately attribute mild hyperprolactinemia to a microprolactinoma without first excluding medication effects, stress, macroprolactinemia, and other secondary causes 6
- Do not forget to refer patients with persistently elevated prolactin levels of unknown etiology to an endocrinologist for further evaluation 1