Prospective Study of High-Dose Cabergoline Treatment of Prolactinomas in 150 Patients

Ono, Masami; Miki, Nobuhiro; Kawamata, Takakazu; Makino, Rena; Amano, Kosaku; Seki, Toshiro; Kubo, Osami; Hori, Tomokatsu; Takano, Kazue

doi:10.1210/jc.2007-2758

Cited by 162 publications

(111 citation statements)

References 32 publications

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“…Therefore, good responders and poor responders in the present study may correspond to the highly sensitive group and the combined group of responsive and partial resistance in the previous report (19) respectively. The increasing doses of cabergoline would normalise PRL levels in our poor responders (22). The third category of prolactinoma patients was the secondary or acquired resistant cases, which initially responded to a dopamine agonist and subsequently became resistant or refractory to treatment.…”

Section: Discussionmentioning

confidence: 92%

Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels

Shimazu

Shimatsu

Yamada

et al. 2012

European Journal of Endocrinology

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Objective: Dopamine agonists normalize prolactin (PRL) levels and reduce tumour size in responsive prolactinoma. However, several cases have shown resistance to dopamine agonists upon initial treatment. Infrequently, prolactinoma initially responds, but then becomes refractory to prolonged treatment (secondary resistance). We investigated the possible mechanisms of resistance to dopamine agonists. Subjects and methods: Twelve cases of prolactinoma were surgically resected and classified according to the responsiveness of PRL levels and tumour size to dopamine agonists: good responders (nZ5), poor responders (nZ5), or secondary resistance (nZ2). We examined the expression of dopamine D 2 receptor (D 2 R) isoform (short: D 2 S and long: D 2 L) mRNA and protein. We investigated DNA methylation patterns in the promoter region of the DRD2 gene. Results: The predominant D 2 R isoform expressed in prolactinoma was D 2 L. Levels of D 2 L mRNA were significantly lower in secondary resistance and poor responders than in good responders. Expression of D 2 R protein was variable among cases. Almost no CpG sites of the DRD2 gene promoter region were methylated. Conclusion: Resistance of prolactinoma to dopamine agonists is correlated with a reduction in D 2 L isoform mRNA levels. Silencing of the DRD2 gene by methylation in the promoter region is unlikely to play a role in dopamine agonist resistance in prolactinoma.

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Section: Discussionmentioning

confidence: 92%

Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels

Shimazu

Shimatsu

Yamada

et al. 2012

European Journal of Endocrinology

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“…Where PRL fails to normalize at a 2.0 mg CAB weekly dose, a stepwise dose increase is recommended, provided that each step improves PRL secretion and/or disease-related symptoms (6,31,33). Some authors failed to observe beneficial effects in increasing CAB dose over 3.5 mg/week (6), whereas others have reported successful increases up to 7.0 mg or more (12,31,33,34). In this study, the use of pharmacological treatment alone was associated with PRL normalization in 22% and tumor shrinkage O50% of the cases.…”

Section: Discussionmentioning

confidence: 99%

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Vroonen

Jaffrain-Rea

Pétrossians

et al. 2012

European Journal of Endocrinology

178

113

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Background: Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. Design and methods: A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB R2.0 mg weekly.

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“…Recently, however, Ono et al have challenged this concept of resistance by proposing an individualized, escalating, high-dose regimen of cabergoline in patients with a poor response to cabergoline (Ono et al, 2008(Ono et al, , 2010. In their studies, cabergoline was started at a standard weekly dosage and schedule, i.e., 0.25-0.5 mg twice a week.…”

Section: Dopamine Agonist-resistant Prolactinomasmentioning

confidence: 99%

Hyperprolactinemia and prolactinoma

Romijn

2014

Handbook of Clinical Neurology

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Prospective Study of High-Dose Cabergoline Treatment of Prolactinomas in 150 Patients

Abstract: Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.

Cited by 162 publications

References 32 publications

Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels

Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Hyperprolactinemia and prolactinoma

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