Effects of bromocriptine on prolactin-secreting pituitary adenomas. Mechanism of reduction in tumor size evaluated by light and electron microscopic, immunohistochemical, and morphometric analysis

Abstract

Prolactin-secreting pituitary adenomas were studied to clarify the mechanism by which bromocriptine reduces tumor size. Patients examined consisted of three groups: Group I (four cases) received no medication, Group II (six cases) continued bromocriptine treatment (10 mg/day for 2 weeks) until the operation, and Group III (five cases) discontinued the treatment 1 week before the operation. Adenomas in Group II showed a variety of degenerative and necrotic changes of tumor cells in addition to marked decrease in volume of individual cell. Adenomas in Group III showed divergent structural changes. Irreversible changes seen in Group II became more pronounced with a marked increase in stromal tissue. Proliferative areas consisting of intermediate-sized cells were found in the scarce stromal tissue. The findings seem to indicate that the reduction in size of prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as from cell loss secondary to necrosis.

Effect of drugs on pituitary ultrastructure

“…Studies on the question whether dopamine agonist treatment induces necrosis of adenoma cells have led to controversial results. Several authors (Barrow et al, 1984;Nissim et al, 1982) concluded that there are no signs of increased necrosis in treated prolactinomas, whereas others (Gen et al, 1983;Ludecke et al, 1983;Mori et al, 1985) reported conspicuous necrobiotic alterations. Morphometric studies in our collection of treated adenomas show (Hallenga et al, 1988) that the rate of cell necrosis was significantly higher after treatment in comparison with preoperatively untreated prolactinomas and inactive adenomas.…”

“…At the ultrastructural level many studies have been undertaken on dopamine agonist-treated adenomas (Fig. 9A,B) (Anniko and Wersall, 1981;Barrow et al, 1984;Bassetti et al, 1984;Landolt, 1984;Larraza et al, 1980;Mori et al, 1985;Nissim et al, 1982;Rengachary et al, 1982;Saitoh et al, 1986b;Schottke et al, 1986;Tindall et al, 1982). Morphometry reveals a reduction of cellular and nuclear size, an increase in number but a reduction in size of secretory granules, an increase in lysosomes, and a reduction of rough endoplasmic reticulum (Figs.…”

“…The number of secretory granules discharged into the intercellular space increases after short-term treatment (Landolt et al, 1985;Saitoh et al, 1986b). The perivascular fibrous tissue accumulates after treatment for more than 3 months (Landolt, 1984;Mori et al, 1985).…”

Treatment for prolactinomas and hyperprolactinaemia: a lifetime approach

“…Optimal duration of therapy and the question if and when therapy can be discontinued are under intensive discussion [55]. Responsible pathomechanisms for persisting remission may be tumour necrosis and fibrosis [56]. Persisting normalization of prolactin has been described for bromocriptine [57].…”

The Dark Side of Dopamine Agonist Therapy in Prolactinoma Management

“…Although no clinical trials have directly compared the relative decreases in pituitary tumor size between the different dopamine agonists, cabergoline and bromocriptine have both been observed to reduce tumor size in more than 80% of patients (2). These agents have been described to efficiently initiate tumor shrinkage by inducing apoptosis, necrosis, and fibrosis of lactotroph cells, resulting in smaller prolactin-secreting cells (3). The clinical effects of this can be dramatic, and improvements in mass effect symptoms and reductions in prolactin levels can be observed just days to weeks after treatment initiation, well before tumor regression is noted on imaging studies.…”