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

Abstract

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.

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

“…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).…”

“…Poor responders were defined as cases neither achieving 95% reduction of basal PRL levels, nor reducing tumour maximal diameter more than 50% of the initial diameter in spite of the treatment of 1 mg/week or more of cabergoline for more than 2 years (nZ5). Secondary resistance was defined as cases showing good responses to a dopamine agonist for more than 2 years and a subsequent increase in tumour size with elevated PRL levels in spite of continuing treatment (nZ2) (5).…”

“…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).…”

Acquired resistance to cabergoline: progression from initially responsive micro to macroprolactinoma

“…In a recent issue of this Journal, Behan et al [1] published a case of secondary resistance to cabergoline in a patient with prolactinoma. We communicate another case of this exceptional circumstance.…”

“…Whereas primary resistance to cabergoline is, therefore, relatively frequent, according to the literature review performed by Behan et al [1], only three previous cases of delayed resistance to dopamine agonists have been convincingly documented in patients on cabergoline treatment. As also observed in our patient, resistance to cabergoline occurred after a long period of good clinical response in all three cases, and transformation from micro to macroprolactinoma was reported in two of them.…”