What is the initial treatment for hyperprolactinemia?

Initial Treatment for Hyperprolactinemia

Cabergoline is the first-line treatment for hyperprolactinemia due to its superior effectiveness in normalizing prolactin levels and better adverse effect profile compared to other dopamine agonists. 1

First-Line Treatment Algorithm

• Before initiating treatment, exclude other causes of hyperprolactinemia such as pregnancy, primary hypothyroidism, and medication effects 1
• Assess baseline macroprolactin levels when serum prolactin is mildly elevated to rule out macroprolactinemia 1
• For patients with large pituitary lesions but normal or mildly elevated prolactin, perform serial dilutions to detect the "high-dose hook effect" which can cause artificially low measurements 1
• Start with cabergoline as the initial treatment:
  • Standard initial dose: 0.25 mg twice weekly 2
  • Gradually increase up to 2 mg/week for most patients 2
  • Cabergoline normalizes prolactin levels in 60-70% of patients and reduces tumor size in 80-88% of cases 1, 2
  • Cabergoline has higher efficacy in normalizing prolactin (83% vs 59% for bromocriptine) 1, 3
  • Significantly better tolerated than bromocriptine (52% vs 72% adverse events) 2, 4

Monitoring and Dose Adjustment

• Obtain baseline echocardiogram before starting treatment 1, 5
• For patients on standard doses (≤2 mg/week), echocardiographic surveillance every 5 years 6, 2
• For patients on higher doses (>2 mg/week), annual echocardiography is recommended 6, 2
• For patients resistant to standard doses:
  • Offer graduated dose increments up to 3.5 mg/week 1, 2
  • In exceptional cases, doses up to 7 mg/week may be considered 1, 2
• Monitor for potential cerebrospinal fluid leak (rhinorrhea) due to medication-induced tumor shrinkage, particularly in tumors that have invaded the sphenoid bone 1

Managing Side Effects

• Small nocturnal dose increments can reduce gastrointestinal intolerance and postural hypotension 6, 2
• Be aware of psychological side effects (mood changes, depression, aggression, hypersexuality, impulse control disorders) which are dose-independent and may be more common in children and adolescents 6, 2
• If cabergoline is not tolerated, bromocriptine can be considered as a second-line option, though it has lower efficacy and more side effects 4, 7

Second-Line Options

• Surgical intervention (transsphenoidal surgery) should be considered when:
  • Patient is unable to tolerate or is resistant to high-dose cabergoline 6, 1
  • Patient develops deteriorating vision on cabergoline 6
  • Dopamine agonist resistance is defined as failure to achieve normal prolactin levels and/or less than 50% reduction in tumor area after 3-6 months of maximally tolerated doses 6, 2
• Radiotherapy is reserved for exceptional cases with growing prolactinoma where other treatments have failed 6, 1

Important Caveats and Pitfalls

• Cabergoline should not be used in patients with a history of cardiac or extracardiac fibrotic disorders 5
• High-dose cabergoline (>2 mg/day) has been associated with cardiac valvulopathy, primarily in patients treated for Parkinson's disease 5
• Discontinue cabergoline if an echocardiogram reveals new valvular regurgitation, valvular restriction, or valve leaflet thickening 5
• Always review medication list before diagnosis and treatment to rule out medication-induced hyperprolactinemia 1
• In pregnancy-induced hypertension, dopamine agonists should not be used unless the potential benefit outweighs the possible risk 5, 8