What is the management of prolactinoma?

Management of Prolactinoma

Cabergoline is the first-line treatment for prolactinomas, starting at 0.25 mg twice weekly and titrating up to 2 mg/week, with the expectation of normalizing prolactin in 83% of patients and achieving tumor shrinkage in 80% of cases. 1

Initial Medical Management

Cabergoline as First-Line Therapy

• Cabergoline is superior to bromocriptine in normalizing prolactin levels (83% vs 59%), resuming ovulatory cycles, and has significantly fewer adverse events (52% vs 72%) 1
• Start with 0.25 mg twice weekly, gradually increasing to a standard maintenance dose of up to 2 mg/week 2
• In children and adolescents, tumors smaller than 13.5 mm typically achieve normalization with conventional doses (up to 2 mg/week), while tumors >20 mm often require surgery 1
• Cabergoline achieves tumor shrinkage in 80-88% of patients, improves visual deficits, resolves pubertal delay, and eliminates headache 1

Dosing Strategy to Minimize Side Effects

• Use small nocturnal dose increments to effectively diminish gastrointestinal intolerance and postural hypotension 1
• This approach avoids unnecessary trials of less effective dopamine agonists like bromocriptine or quinagolide 1

Management of Resistant Cases

Dose Escalation Protocol

• For patients resistant to standard doses (up to 2 mg/week), offer graduated dose increments up to 3.5 mg/week 1, 2
• In exceptional cases, doses up to 7 mg/week may be used, though some evidence suggests little additional benefit above 3.5 mg/week in adults 1
• Higher doses (up to 12 mg/week) have been tried but remain well below the 21 mg/week used for Parkinson's disease 1

Defining Treatment Resistance

• Dopamine agonist resistance is defined as:
  • Failure to achieve normoprolactinemia (biochemical resistance) AND/OR
  • Less than 50% reduction in tumor area or less than 30% reduction in longest tumor diameter
  • After 3-6 months of maximally tolerated doses (at least 2 mg/week) 1, 3
• Resistance correlates directly with tumor size and prolactin levels but is independent of MEN1 mutation status 1

Surgical Intervention

Indications for Surgery

• Following multidisciplinary discussion, offer surgery when:
  • Patient is unable to tolerate or is resistant to high-dose cabergoline 1
  • Vision deteriorates or does not improve on cabergoline 1
  • Patient is non-adherent to long-term medication or expresses preference for surgery 1

Surgical Outcomes

• Transsphenoidal surgery achieves remission in 83% of microprolactinomas and 60% of intrasellar macroprolactinomas in high-volume surgical centers 1
• Pediatric series report lower surgical remission rates than adults, likely due to higher incidence of proportionately larger prolactinomas 1
• Tumor size negatively predicts surgical remission rates, with smaller adenomas more often cured by surgery alone 1
• Any residual post-operative hyperprolactinemia is typically more responsive to dopamine agonists than pre-operatively 1

Radiotherapy

• Reserve radiotherapy for exceptional patients with growing prolactinoma where other treatment modalities have been exhausted 1
• The main indication is control of tumor growth; normalization of prolactin levels is a secondary objective 1
• Following multidisciplinary discussion, offer radiotherapy if surgery is not an option 1

Monitoring Requirements

Cardiac Surveillance

• Obtain a baseline echocardiogram before starting cabergoline treatment 3
• For patients on >2 mg/week: annual echocardiography with cardiac auscultation is required due to risk of cardiac valvulopathy 2, 4
• For patients on ≤2 mg/week: echocardiographic surveillance can be reduced to every 5 years 2, 4

Biochemical and Imaging Monitoring

• Measure serum prolactin levels every 3-6 months until stabilized 3
• For macroprolactinomas, repeat MRI 3-6 months after starting cabergoline 3
• Monitor clinical symptoms including menstrual history, galactorrhea, libido, and visual fields 1, 3

Special Monitoring Considerations

• Watch for cerebrospinal fluid leak (rhinorrhea) in patients with prolactinomas invading sphenoid bone, which can occur after medication-induced tumor shrinkage (mean 3.3 months, range 3 days-17 months) 1
• Detection of β2-transferrin or β-trace protein in nasal secretions confirms CSF leak and may require urgent intervention 1
• Monitor for psychological side effects (mood changes, depression, aggression, hypersexuality, impulse control disorders), which may be more common in children and adolescents 1, 3

Treatment Discontinuation

• For patients with normalized prolactin levels for at least 2 years and no visible tumor on MRI, consider gradual dose reduction with continued prolactin monitoring for at least 2 more years 3
• After cabergoline withdrawal, monitor prolactin levels at 3-6 month intervals initially to detect biochemical relapse 3
• Younger patients and those with high serum prolactin concentrations at diagnosis are less likely to achieve complete remission and successful discontinuation 1

Critical Pitfalls to Avoid

• Do not use cabergoline for prevention of physiological lactation or in patients with uncontrolled hypertension, as serious adverse events including hypertension, myocardial infarction, seizures, and stroke have been reported in postpartum women 5
• Symptomatic hypotension can occur, with decreases in supine systolic pressure of >20 mmHg observed in almost 30% of patients; exercise caution when driving or operating machinery during initial treatment 5
• Apoplexy has been described during cabergoline therapy in both adults and children 1
• Complete pituitary evaluation is mandatory before treatment, as prolactin-secreting adenomas may expand during pregnancy, causing optic nerve compression that may require emergency pituitary surgery 5