Failure of bromocriptine to maintain reduction in size of a macroprolactinoma.

Breidahl, H. D.; Topliss, Duncan J.; Pike, J. Wesley

doi:10.1136/bmj.287.6390.451

Cited by 57 publications

(21 citation statements)

References 14 publications

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“…Only six such patients have been reported in the literature (excluding malignant transformation) (3,4,5,6,7). The possible explanations for acquired non-responsiveness include non-compliance, onset of gonadal steroid replacement that causes dopamine resistance in the lactotrophs, and, rarely, transformation to carcinoma (37,41).…”

Section: Discussionmentioning

confidence: 99%

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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: 99%

“…There have been very few reported cases of prolactinoma exhibiting secondary resistance, i.e. cases that show an initial response to dopamine agonists, but then become refractory with prolonged treatment (3,4,5,6,7).…”

Section: Introductionmentioning

confidence: 99%

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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“…A case described by Breidahl et al (1983) was probably the first report of true secondary resistance to bromocriptine therapy. After 10 months of bromocriptine treatment, which had normalised serum prolactin concentration and decreased tumour size, there was an increase in both parameters despite increasing doses of up to 40 mg daily.…”

Section: Discussionmentioning

confidence: 94%

Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review

et al. 2009

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Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

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“…Although partial responses [11] and even relapses [18,19] have been reported in pa tients taking bromocriptine, we have not yet encountered this, and all apparent failures of treatment have been due to poor drug com pliance. Some tumours are probably less sen sitive to bromocriptine than others and in our experience those patients whose prolactin levels fell less than 90% after 6 weeks needed more than 10 mg of bromocriptine to main tain a progressive fall in prolactin.…”

Section: Discussionmentioning

confidence: 96%

Extrasellar Prolactinomas: Successful Management of 24 Patients Using Bromocriptine

Sieck¹,

Niles²,

Jinkins

et al. 1986

Horm Res

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24 patients with an extrasellar prolactinoma (mean prolactin 4,722 ng/ml), 8 of whom had previously had surgery, received 5–40 mg bromocriptine daily for 13–252 weeks. The mean prolactin level had fallen 89% at 2 days, 95% at 6 weeks, and 15 patients achieved normal values. Tumor shrinkage occurred in all 9 patients rescanned within 2 weeks and later was documented in 23; in 18 the extrasellar tumour disappeared. 12 patients had visual abnormalities; 7, including 2 who had been completely blind, improved within 1 week. 2 patients had normal prolactin levels after withdrawal of bromocriptine, 1 following radiotherapy and the other during two uncomplicated pregnancies. Bromocriptine is safe and effective. We conclude that medical treatment should always precede surgery unless pituitary apoplexy causes sudden deterioration of vision. Most patients will subsequently require radiotherapy or surgery for permanent cure.

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Failure of bromocriptine to maintain reduction in size of a macroprolactinoma.

Cited by 57 publications

References 14 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

Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review

Extrasellar Prolactinomas: Successful Management of 24 Patients Using Bromocriptine

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