Low Doses of Dopamine Agonists in the Long-Term Treatment of Macroprolactinomas

Liuzzi, Antonio; Dallabonzana, D.; Oppizzi, G.; Verde, G.; Cozzi, Renato; Chiodini, P. G.; Luccarelli, G.

doi:10.1056/nejm198509123131103

Cited by 139 publications

(62 citation statements)

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“…The pharmacological characterization of binding, as reported in Table 2 (Table 3) and that administration of bromocriptine (0.01 ug/g) after NGF resulted in a decrease of plasma PRL levels (data not shown). DISCUSSION D-2 receptor agonists are effective in lowering plasma PRL levels in patients with prolactinomas (27)(28)(29)(30)(31). Although the majority of prolactinoma patients respond to pharmacological therapy, there is a population of nonresponders who require surgical intervention.…”

Section: Resultsmentioning

confidence: 99%

“…The first line of therapy of patients with prolactinoma was neurosurgical intervention (25,26) until the breakthrough discovery that D-2 agonists, such as bromocriptine, are effective both in lowering PRL levels and in reducing tumor size (27)(28)(29)(30)(31). The pharmacological therapy, however, does not invariably reduce PRL secretion in prolactinoma patients; in fact, 10-15% of patients are nonresponders and may require the surgical approach (24,32).…”

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confidence: 99%

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Nerve growth factor suppresses the transforming phenotype of human prolactinomas.

Missale

Boroni

Losa

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The most effective therapy of human prolactinomas is represented by dopamine D-2 receptor agonists; there is, however, a population of nonresponder patients who require surgical intervention. In the present study, we report that prolactinomas totally resistant to pharmacological therapy have a high potential of both growing in soft agar and forming tumors in nude mice and lack D-2 receptors for dopamine. These tumors express the receptors for nerve growth factor (NGF) and are sensitive to its differentiating activity. After exposure to NGF for 4 days, prolactinoma cells decreased their proliferation rate, lost their capability to form colonies in soft agar, lost their tumorigenic activity in nude mice, and reexpressed the lactotroph-specific D-2 receptor protein inhibiting prolactin release. These effects were permanent after NGF withdrawal and were reproducible in vivo in nude mice transplanted with the tumors. NGF in fact remarkably and lastingly depressed tumor growth and induced expression of D-2 receptors when injected intravenously once a day for 5 days into prolactinoma-bearing nude mice. These data suggest that NGF may induce a long-lasting switch of gene expression in human prolactinomas, modifying their transforming phenotype and reverting them to more differentiated, less malignant, dopamine-sensitive lactotroph-like cells. The possibility thus arises that short-term treatment with NGF may restore the refractory patients to conventional pharmacological therapy with D-2 agonists.Nerve growth factor (NGF) is a neurotrophic protein that promotes the growth, differentiation, and survival of peripheral sympathetic neurons, the majority of neural crestderived sensory nerve cells (1-3), and the ascending cholinergic neurons ofthe basal forebrain (4)(5)(6). NGF also converts the pheochromocytoma cell line PC-12 into a sympathetic neuronal phenotype (7,8) and exerts a differentiating action on cells of the immune system (9, 10). The effects of NGF are directly dependent on initial binding to specific cell-surface receptors. Two protein components are required to form the high-affinity ligand-binding site for NGF: the 140-kDa protein-tyrosine kinase, which is encoded by the trkA protooncogene (gpl40trk) (11-13), and the 75-kDa glycoprotein gp75NGFR (14,15 We report here that bromocriptine-resistant prolactinomas lack D-2 receptors. Since these tumors express NGF receptors, we investigated whether they were sensitive to the differentiating action of the neurotrophic factor. The results show that exposure of prolactinoma cells to NGF resulted in their conversion into a more differentiated lactotroph-like phenotype reexpressing the D-2 receptor protein. MATERIALS AND METHODS Preparation of Prolactinoma Cell Cultures and Treatmentwith NGF. Tumor specimens were obtained from eight patients refractory to bromocriptine and five sensitive subjects who did not tolerate the drug. The five sensitive subjects responded to bromocriptine at 5-10 mg/day with a normalization of plasma PRL levels. Three of them were for...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Nerve growth factor suppresses the transforming phenotype of human prolactinomas.

Missale

Boroni

Losa

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…2,34 The dopamine agonists (bromocriptine, pergolide, cabergoline) normalize prolactin levels in 67 to 89% of patients. 2,31,33,47 Tumors recede by at least 50% in nearly two thirds of patients, and visual field deficits improve in 90%. 33 Tumor reduction occurs within 6 weeks in the majority of patients.…”

Section: Role Of Gks In Multimodal Therapymentioning

confidence: 99%

Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach

Jane¹,

Vance²,

Woodburn³

et al. 2003

FOC

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Object Surgical and medical therapies successfully achieve biochemical remission in the majority of patients with secretory pituitary adenomas. Nevertheless, continued hypersecretion after first-line therapy occurs and requires adjunctive therapy to prevent morbidity and premature mortality. For patients in whom medical and surgical therapy have failed, gamma knife surgery (GKS) is performed with the goal of controlling tumor growth and excess growth hormone (GH) production. The authors report their experience with GKS in patients in whom surgical and medical therapies failed. Methods The neuroendocrine service at the University of Virginia has treated 220 patients with secretory adenomas. The authors evaluated the biochemical results in patients with acromegaly followed for greater than 18 months (64 patients) as well as those with Cushing disease (45 patients), Nelson syndrome (14 patients with adequate follow up [27 overall]), and prolactinomas (19 patients) followed for at least 12 months posttreatment. Biochemical remission occurred in 36% of patients with GH-secreting adenomas, 73% of those with Cushing disease, 14% of those with Nelson syndrome, and 11% of those harboring prolactinomas. Recurrence after biochemical remission was documented in four patients with Cushing disease. New hormonal deficits have occurred in 28% of patients with acromegaly, 31% with Cushing disease, 36% with Nelson syndrome, and 21% with prolactinomas. Minor visual deterioration developed in one patient with Cushing disease. Conclusions Gamma knife surgery offers an important treatment modality in patients with secretory adenomas refractory to surgical and medical interventions.

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“…Dopamine agonist therapy is the primary treatment for macroprolactinomas and has been in use for over 15 years. Bromocriptine, the only dopamine agonist currently approved for this indication in the United States, normalizes serum PRL levels in 67-79% of patients with PRL-secreting macroadenomas (1,2). This is associated with reduction in tumor size in over 75% of patients, restoration of gonadal function, cessation of galactorrhea, and improvement in visual defects in the majority of patients (1,2).…”

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confidence: 99%

Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.

Molitch

Vance

Cannistraro

et al. 1996

The Journal of Clinical Endocrinology & Metabolism

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Low Doses of Dopamine Agonists in the Long-Term Treatment of Macroprolactinomas

Cited by 139 publications

References 14 publications

Nerve growth factor suppresses the transforming phenotype of human prolactinomas.

Nerve growth factor suppresses the transforming phenotype of human prolactinomas.

Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach

Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.

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