Dopamine agonist therapy for prolactinomas: do we need to rethink the place of surgery in prolactinoma management?

Abstract

The current treatment paradigm for prolactinomas involves dopamine agonist (DA) therapy as the first-line treatment, with surgical resection reserved for cases where there is DA failure due to resistance or intolerance. This review highlights how DA therapy can be optimised to overcome its increasingly recognised pitfalls, whilst also addressing the potential for expanding the use of surgery in the management of prolactinomas. The first part of the review discusses the limitations of DA therapy, namely: DA resistance; common DA side effects; and the rare but serious DA-induced risks of cardiac valvulopathy, impulse control disorders, psychosis, CSF rhinorrhoea and tumour fibrosis. The second part of the review explores the role of surgery in prolactinoma management with reference to its current second-line position and recent calls for surgery to be considered as an alternative first-line treatment alongside DA therapy. Randomised trials comparing medical versus surgical therapy for prolactinomas are currently underway. Pending these results, a low surgical threshold approach is herein proposed, whereby DA therapy remains the default treatment for prolactinomas unless there are specific triggers to consider surgery, including concern regarding DA side effects or risks in vulnerable patients, persistent and bothersome DA side effects, emergence of any serious risks of DA therapy, expected need for long-term DA therapy, as well as the traditional indications for surgery. This approach should optimise the use of DA therapy for those who will most benefit from it, whilst instituting surgery early in others in order to minimise the cumulative burden of prolonged DA therapy.

Surgery as first-line treatment for prolactinoma? Discussion of the literature and results of a consecutive series of surgically treated patients

“…Based on the good results, the question of whether the indication for surgery for prolactinomas should be reevaluated and whether minimally invasive transsphenoidal surgery should be offered as a first-line treatment option (especially for microprolactinomas) has been increasingly discussed by physicians involved in the treatment of prolactinomas in recent years [ 6 , 7 , 9 , 17 , 22 , 26 , 27 ].…”

“…Although the majority of patients experience side effects, these effects tend to resolve and only a small proportion of patients ultimately have to discontinue treatment due to side effects [ 5 , 6 ]. More serious risks of dopamine agonists include valvular heart disease, psychosis, and impulse control disorder, but more research is needed to better understand the relationship of these complications to medical treatment [ 7 ]. Furthermore, CSF rhinorrhea can occur as a complication of medical therapy for prolactinoma in cases where large tumors have led to the destruction of the skull base and a shrinking tumor under dopamine agonists opens skull base defects with subsequent CSF leakage.…”

Cabergoline-associated valvulopathy of the tricuspid valve in the treatment of prolactinoma

“…Notably, these data were collected without standardisation of echocardiographic measurement and also lack detail regarding valve morphology and mobility ( Stiles et al 2019 ). It is unclear if this finding in the absence of the remaining diagnostic triad represents an early, pre-symptomatic stage of CAV or is unrelated ( De Sousa 2022 ).…”

“…Early diagnosis of CAV with discontinuation of ergot-derived DA can allow recovery of valvulopathy, especially in monovalvular cases, or prevention of valvular deterioration, compared to drug continuation ( Zanettini et al 2011 ). Quinagolide, a non-ergot-derived DA has not been associated with this effect and may be considered as an alternative, particularly in aggressive tumours where medical treatment cannot be withdrawn ( De Sousa 2022 ).…”

Gender-specific prolactin thresholds to determine prolactinoma size: a novel Bayesian approach and its clinical utility

“…Dopamine agonists (DAs) are the first-line choice, with strong efficacy to achieve both serum prolactin (PRL) normalization and adenoma size reduction, even to the extent of definitive cure (4). In recent years, surgery was increasingly considered as first-line therapy in patients who have a reasonable likelihood of cure, with the aim of minimizing the need for continuous DA therapy in the long term (2,3,5,6), including potential side effects (7)(8)(9).…”