Treatment Of Prolactinoma

An algorithm for the management of prolactinoma is given in Fig. 1.

Treatment Indications

Most patients with prolactinoma require active treatment. Infertility, menstrual disturbance with long-standing hypogonadism (risk of secondary osteoporosis), troublesome galactorrhea, an enlarging pituitary tumor and tumor

Pituitary Adenoma Treatment Algorithm
Fig. 1. Management algorithm for prolactinoma.

pressure effects (particularly visual failure) are all indications for treatment. As will be seen, dopamine agonist drugs are now indicated as primary medical therapy for patients with prolactinomas of all sizes. However, an important exception is the patient with a pituitary macrolesion and minor PRL elevation, who is most likely to have a nonfunctioning pituitary adenoma requiring surgery for decompression and histologic diagnosis. It may be reasonable to simply observe some patients with microprolactinomas, particularly if circulating sex steroid concentrations are judged to be adequate and BMD is normal.

Dopamine Agonists

The introduction of medical therapy with dopamine agonists revolutionized the treatment of patients with prolactinoma. The first such drug was bromocriptine, a semisynthetic ergopeptine derivative, introduced in 1971. On a global basis, this probably remains the most widely used dopamine agonist, but the introduction of other longer acting and better tolerated drugs, such as cabergoline and quinagolide, is altering this pattern, at least in the Western world. Many UK endocrine units now use cabergoline as first-choice dopamine agonist after a large comparative study with bromocriptine, which convincingly demonstrated its superiority in terms of tolerability, patient convenience, and possibly also efficacy (14). All dopamine agonists may produce unwanted side effects, including, in decreasing order of importance, upper gastrointestinal disturbance (especially nausea), postural hypotension, constipation, nasal stuffiness, and Raynaud's phenomenon. These can be minimized by using an incremental dosage schedule and taking tablets during meals.

Cabergoline and quinagolide are newer dopamine agonists, which have been licensed in the UK during the last decade. Table 3 summarizes the recent prospective comparative studies of these agents, both with each other and with bromocriptine. Bromocriptine normalized PRL in 57% of patients, compared with 85% taking cabergoline and 78% taking quinagolide. Cabergoline was better tolerated, with mild adverse effects reported in only 37% and fewer than 3% of patients withdrawing from therapy. Bromocriptine caused mild adverse effects in 67%, with 13% of patients needing to cease therapy. Table 4 provides an overview of recent publications addressing cabergoline efficacy and tolerabil-ity. In pooled data from 1485 patients (972 with microadenomas and 513 with macroadenomas), PRL was normalized in 87% of patients. Adverse effects were noted in 26% of patients, but only 1.7% of patients had to discontinue therapy. It is notable that cabergoline was effective (approx 80%) and well tolerated (>90%) in the majority of patients with bromocriptine resistance (164 patients) and bromocriptine intolerance (267 patients). Colao and colleagues reported that 17 of 20 patients resistant to quinagolide achieved normoprolactinemia during cabergoline therapy, although a proportion may have been poorly compliant with quinagolide (29).

Bromocriptine is used in a dose of 2.5 mg two or three times daily. It is now clear that the doses of 20-40 mg/d used in early studies are no more efficacious and produce more side-effects. Cabergoline is usually effective in a dose of 0.5-1.0 mg once or twice weekly and quinagolide in a once-daily dose of75-150 ^g. To minimize side effects, patients should be advised to take these two newer

Table 3

Prospective Comparative Studies of Bromocriptine, Cabergoline, and Quinagolide

Table 3

Prospective Comparative Studies of Bromocriptine, Cabergoline, and Quinagolide

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