What is the management and treatment of hyperprolactinemia (elevated prolactin levels)?

Management and Treatment of Hyperprolactinemia

Dopamine agonists are the first-line treatment for hyperprolactinemia, with cabergoline being more effective and better tolerated than bromocriptine in most cases. 1, 2

Diagnosis of Hyperprolactinemia

Clinical Presentation

Hyperprolactinemia presents with different symptoms depending on sex and age:

• Women: Delayed or arrested puberty, galactorrhea, menstrual disturbances (oligomenorrhea or amenorrhea), infertility 1
• Men: Hypogonadism, decreased libido, erectile dysfunction, infertility, gynecomastia 1
• Both sexes: Headaches and visual field defects (with macroadenomas) 1

Diagnostic Workup

1. Serum prolactin measurement: A single blood sample collected at any time of day is sufficient 1

   • For modestly elevated levels, consider serial measurements to exclude stress-related elevation
   • Use age-specific and sex-specific reference ranges

2. Rule out secondary causes:

   • Medications (antipsychotics, metoclopramide, verapamil)
   • Hypothyroidism (check thyroid function)
   • Renal or hepatic impairment
   • Pregnancy (in women of reproductive age)
   • Chest wall stimulation/trauma 1

3. Additional testing:

   • In patients with low testosterone, measure luteinizing hormone (LH) levels 1
   • If testosterone is low with low/normal LH, measure prolactin 1
   • Consider macroprolactin testing for mildly elevated prolactin without symptoms 1
   • MRI of pituitary if prolactin >4,000 mU/L (188 μg/L) or with symptoms of mass effect 1

Treatment Algorithm

1. Prolactinomas

Microprolactinomas (<10mm)

• First-line: Dopamine agonist therapy 2, 3

  • Cabergoline: Starting dose 0.25-0.5 mg once or twice weekly
  • Bromocriptine: Starting dose 1.25-2.5 mg daily, increasing to 2.5 mg 2-3 times daily
  • Cabergoline is preferred due to better efficacy and tolerability 2, 3

• Monitoring:

  • Prolactin levels every 3-6 months
  • MRI after 1 year and then after 5 years if stable 2

Macroprolactinomas (≥10mm)

• First-line: Dopamine agonist therapy (same medications as above) 2, 3

• Monitoring:

  • MRI after 3 months to verify tumor size reduction
  • Then after 1 year, yearly for 5 years, and every 5 years thereafter if stable 2
  • More frequent monitoring if symptoms worsen

• Surgery considerations:

  • Reserved for patients intolerant or resistant to dopamine agonists
  • When there is mass effect despite medical therapy
  • Acute complications (apoplexy, CSF leak) 3, 4

2. Medication-Induced Hyperprolactinemia

• If possible, discontinue the causative medication
• If medication cannot be withdrawn:
  • Confirm absence of pituitary adenoma
  • Consider sex hormone replacement to prevent osteoporosis
  • Avoid dopamine agonists unless absolutely necessary 2

3. Idiopathic Hyperprolactinemia

• Treat with dopamine agonists if symptomatic (amenorrhea, galactorrhea, infertility) 2, 3
• May attempt withdrawal of medication after 2 years of normal prolactin levels

Medication Details

Cabergoline

• Advantages: Better efficacy (normalizes prolactin in >90% of cases), better tolerated, once or twice weekly dosing 2, 3
• Monitoring: Echocardiogram recommended every 6-12 months for patients on long-term therapy due to risk of cardiac valvulopathy (especially at doses >2mg/day) 5
• Caution: Risk of fibrotic complications (cardiac valvulopathy, pleural, pericardial, retroperitoneal fibrosis) 5

Bromocriptine

• Advantages: Longer history of use, established safety in pregnancy 6, 7
• Disadvantages: Multiple daily dosing, more side effects (nausea, dizziness, headache) 2
• Caution: Risk of hypotension, particularly during initial treatment 6

Special Considerations

Pregnancy

• Bromocriptine is preferred when planning pregnancy due to more safety data 7, 4
• Dopamine agonists should be discontinued once pregnancy is confirmed unless there's risk of significant tumor growth 6
• Pregnancy is generally safe and may actually benefit patients with prolactinomas by reducing prolactin levels 7

Treatment Duration and Discontinuation

• After 2-3 years of normal prolactin levels and significant tumor shrinkage, consider trial of medication discontinuation
• Only 20-30% of patients maintain normal prolactin levels after stopping treatment 2
• Continue monitoring prolactin levels after discontinuation
• Alternative approach: Reduce dose to lowest effective level that maintains normal prolactin 2

Pitfalls and Caveats

• Don't overlook macroprolactinemia as a cause of elevated prolactin without symptoms
• Men with total testosterone <150 ng/dL and low/normal LH should undergo pituitary MRI regardless of prolactin levels 1
• Severe primary hypothyroidism can cause pituitary enlargement that mimics prolactinoma 1
• Stress-induced elevations can be ruled out by serial sampling
• Patients on dopamine agonists should be monitored for development of impulse control disorders