Withdrawal of bromocriptine after long‐term therapy for macroprolactinomas; effect on plasma prolactin and tumour size

Dopamine agonists (DA) are the mainstay of treatment for patients with prolactinomas. To describe the efficacy of treatment and the outcomes of DA withdrawal. Retrospective review of electronic medical records of patients with prolactinomas from 1985 to 2009. Seventy-nine patients (17 men/62 women), aged 35.3 ± 1.6 years at diagnosis were studied. The mean follow-up time was 84.7 ± 9.2 months (range 0-336). The mean initial size of microadenomas was 0.74 ± 0.10 cm (range 2.41 ± 0.39) and of macrodenomas 2.41 ± 0.39 cm (range 1.1-8) and serum prolactin (PRL) levels were 112 ± 19 and 263 ± 59 ng/ml, respectively (normal range 0-40). Fifty-one (65%) prolactinomas were micro- and 28 (35%) were macroadenomas. DA led to a decrease in adenoma size in 71% of them, while 53% of microadenomas were not visible during follow-up. In 26 patients, DA withdrawal was decided. After therapy of >24 months and a mean follow-up time of 49 ± 11 months (range 3-168), 15 subjects (58%) showed no recurrence of hyperprolactinemia. Higher remission rates, although not statistically significant, were observed with cabergoline (75%). The mean PRL levels before DA discontinuation were 12.2 ± 2.3 ng/ml (range 0.5-44.7) and after discontinuation they were significantly lower than pre-treatment values. Recurrence of hypeprolactinemia was evident during the first year in all but one patient. Remission rates were not associated with age or size of adenoma at diagnosis, initial or before DA discontinuation PRL levels and duration of treatment. DA withdrawal was followed by remission of hyperprolactinamia in about half of patients after >2 years of treatment.

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“…These outcomes are better than usually been reported (mean 29%, ranging from 7 to 69% [5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Discussioncontrasting

confidence: 42%

Long term follow-up of patients with prolactinomas and outcome of dopamine agonist withdrawal: a single center experience

et al. 2011

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“…Of the 30 patients whose PRL levels fell to normal levels, 21 maintained the condition with low-dose bromocriptine (0.625-10 mg/d), and their PRL levels and tumor volumes were well controlled. According to the reports of bromocriptine withdrawal [32][33][34][37][38], 14 patients with normal PRL level and absent tumor on MR images withdrew from bromocriptine treatment in our group, and renewed tumor growth and recurrent hyperprolactinemia were not found during an average period of 1.5-year follow-up. About 18 patients with residual tumor invading the cavernous sinus had no related compromising symptoms, of which seven patients maintained normal PRL levels with low-dose bromocriptine treatment.…”

Section: Bromocriptine Reduction or Withdrawalcontrasting

confidence: 48%

Five years follow-up of invasive prolactinomas with special reference to the control of cavernous sinus invasion

et al. 2007

Pituitary

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About three-fourths of prolactinomas with CS invasion can be effectively controlled not only with regard to tumor volume disappearance but also in serum PRL normalization. Residual tumor in the CS areas with PRL normalization and no pressure symptoms can be treated with low-dose of bromocriptine so as to achieve long-term tumor volume control and endocrine control. Great attention should be paid to CS residual tumors accompanying the empty sella, especially in cases with optic chiasmal herniation.

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“…vanЈt Verlaat et al (6) observed reduction of tumor nests and also acellular spaces. They also speculate that BRC might have a cytostatic effect related to short-term therapy, and a cytocidal one to long- term therapy, and suggest that this finding may explain the maintenance of normoprolactinemia after drug withdrawal.…”

Section: Discussionmentioning

confidence: 97%

Long-Term Follow-Up of Prolactinomas: Normoprolactinemia after Bromocriptine Withdrawal

Passos

Souza

Musolino

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

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Bromocriptine (BRC) and other dopamine agonist drugs are the first-choice treatment for prolactinomas. However, the major disadvantage is the need for prolonged therapy. We retrospectively studied 131 patients [62 microprolactinoma (MIC), 69 macroprolactinoma (MAC)], who achieved serum prolactin (PRL) normalization during BRC use. Twenty-seven percent of them (31% MIC and 69% MAC) underwent previous surgery. Twenty-seven patients (20.6%: 25.8% MIC and 15.9% MAC) persisted with normoprolactinemia after a median time of 44 months of BRC withdrawal. The median time of BRC use was 47 months. There were no statistically significant differences regarding age, gender, BRC initial dose, length of BRC use, tumor size, pregnancy during treatment, previous surgery, or radiotherapy among patients who persisted with normoprolactinemia and those who did not, using both univariate and multivariate analysis. BRC-induced prolactinoma cell alterations are highly controversial; and so, whether the mechanism of PRL normalization after BRC withdrawal is related to BRC use or whether it is attributable to natural history is a matter for debate. A periodic assessment of PRL levels during BRC (and other dopamine-agonist drugs) withdrawal is recommended to avoid the unnecessary maintenance of therapy in a subset of patients with prolactinomas.

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Withdrawal of bromocriptine after long‐term therapy for macroprolactinomas; effect on plasma prolactin and tumour size

Cited by 74 publications

References 17 publications

Long term follow-up of patients with prolactinomas and outcome of dopamine agonist withdrawal: a single center experience

Long term follow-up of patients with prolactinomas and outcome of dopamine agonist withdrawal: a single center experience

Five years follow-up of invasive prolactinomas with special reference to the control of cavernous sinus invasion

Long-Term Follow-Up of Prolactinomas: Normoprolactinemia after Bromocriptine Withdrawal

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