Recent studies reveal an increased risk of cardiac valve regurgitation in patients with Parkinson disease who were treated with high doses of cabergoline or pergolide but not with bromocriptine (296,297). Higher doses and a longer duration of therapy were associated with a higher risk of valvulopathy. It is postulated that 5HT2b-receptor stimulation leads to fibromyoblast proliferation (298). A recent cross-sectional study showed a higher rate of asymptomatic tricuspid regurgitation among cabergoline-treated patients compared to untreated patients with newly diagnosed prolactinomas as well as normal controls (299,300).
The demonstrated relative safety of bromocriptine in reproductive-aged women and during more than 2,500 pregnancies suggest bromocriptine is the first choice for hyperprolactinemia and micro-and macroadenomas (301).
When bromocriptine or cabergoline cannot be used, other medications such as pergolide or metergoline may be used. In patients with a microadenoma who are receiving bromocriptine therapy, a repeat MRI scan may be performed 6 to 12 months after prolactin levels are normal, if indicated. Further MRI scans should be performed if new symptoms appear.
Discontinuation of bromocriptine therapy after 2 to 3 years may be attempted in a select group of patients who have maintained normoprolactinemia while on therapy (302,303). In a retrospective series of 131 patients treated with bromocriptine for a median of 47 months, normoprolactinemia was sustained in 21% at a median follow-up of 44 months after treatment discontinuation (303). Discontinuation of cabergoline therapy was successful in patients treated for 3 to 4 years who maintained normoprolactinemia (304). In cabergoline discontinuers who met stringent inclusion criteria, a recurrence rate of 64% was noted (305). A recent meta-analysis involving 743 patients noted sustained normoprolactinemia in only a minority of patients (21%) after discontinuation. Patients with 2 years or more of therapy before discontinuation and no demonstrable tumor visible on MRI had the highest chance of persistent normoprolactinemia (306). Recurrence rates are higher for macroadenomas (as compared to microadenomas or hyperprolactinemia without adenoma) after cessation of bromocriptine or cabergoline, warranting close follow-up with serum prolactin and MRI after cessation of therapy. In patients with macroadenomas, withdrawal of therapy should proceed with caution, as rapid tumor reexpansion may occur.
Macroadenomas are pituitary tumors that are larger than 1 cm in size. Bromocriptine is the best initial and potentially long-term treatment option, but transsphenoidal surgery may be required. High-dose cabergoline therapy was used in bromocriptine resistant or intolerant macroadenoma patients with success; however, cautions remain regarding the development of cardiac valve abnormalities (307).
Evaluation for pituitary hormone deficiencies may be indicated. Symptoms of macroadenoma enlargement include severe headaches, visual field changes, and, rarely, diabetes insipidus and blindness. After prolactin has reached normal levels following ergot alkaloid treatment, a repeat MRI is indicated within 6 months to document shrinkage or stabilization of the size of the macroadenoma. This examination may be performed earlier if new symptoms develop or if there is no improvement in previously noted symptoms.
Medical Treatment Treatment with bromocriptine decreases prolactin levels and the size of macroadenomas; nearly one-half show a 50% reduction in size, and another one-fourth show a 33% reduction after 6 months of therapy. Because tumor regrowth occurs in more than 60% of cases after discontinuation of bromocriptine therapy, long-term therapy is usually required.