Long-term treatment of prolactin-secreting macroadenomas with pergolide.

Abstract

Although most PRL-secreting pituitary tumors are microadenomas at presentation, many, and particularly those in men, are macroadenomas at the time of diagnosis. Microprolactinomas typically present because of PRL-induced menstrual disturbance or galactorrhea in women and symptoms of hypogonadism in men. Macroprolactinomas (i.e. tumors .10 mm), however, often present because of symptoms of mass effect by the tumor, such as visual field loss, headache, other neurological symptoms or hypopituitarism. Therefore, the initial treatment of macroprolactinomas includes tumor shrinkage with relief of neurological symptoms, in addition to the lowering of PRL and restoration of gonadal function. Medical therapy with dopamine agonists is now the preferred primary treatment of patients with prolactinomas. The dopamine agonist bromocriptine (BC) has been available and extensively used in the United States since the early 1980s. BC normalizes PRL levels and gonadal function in the majority of patients and reduces tumor size in up to 70–80% of patients with prolactinomas (1–3). Disadvantages to its use include side effects such as nausea, postural hypotension, nasal stuffiness, and headache in up to 10% of patients, as well as the twice or thrice daily dosing administration required. Recently, the longer-acting dopamine agonist cabergoline has been introduced in the United States for therapy of macroprolactinomas. Cabergoline has been shown to normalize PRL levels in up to 73–83% of patients and to reduce tumor size in most patients (4–6). Cabergoline seems to be better tolerated than BC (6). Another ergoline derivative, pergolide mesylate, effectively inhibits PRL secretion and is an option for the medical treatment of prolactinomas. This dopamine agonist is approximately 100 times more potent than BC and suppresses PRL secretion for up to 24 h after a single dose (7, 8), allowing effective control of hyperprolactinemia with once daily dosing. Pergolide is approved in the United States only for the therapy of Parkinson’s disease, where it has been used safely at doses more than 10 times those used for PRL-secreting tumors (9). It has advantages over BC in that it only requires once-a-day dosing and is approximately one fifth the cost. In short-term studies, pergolide has been shown to effectively lower PRL levels. Few studies, however, have examined the long-term outcome of pergolide therapy of macroprolactinomas. The number of macroprolactinomas, followed with imaging studies, is also very small, and no studies have reported tumor shrinkage with pergolide documented by magnetic resonance imaging (MRI). Before the availability of cabergoline, we treated many patients with pergolide as first-line therapy and have documented its efficacy in correcting endocrine abnormalities and in shrinking macroprolactinomas. Even though cabergoline may now be first-line therapy in many patients, based on our experience, pergolide remains an important alternative for the treatment of prolactinomas in the United States. Therefore, we present one case in detail of a patient with a very large macroprolactinoma treated with pergolide alone and then report our experience with pergolide for the long-term treatment of 22 patients with macroprolactinomas.