Treatment with low doses of cabergoline is not associated with increased prevalence of cardiac valve regurgitation in patients with hyperprolactinaemia

The increased risk of cardiac valve disease in patients treated for Parkinson's disease with cabergoline has raised concerns about the safety of treatment with ergot-derived dopamine agonists in patients with endocrine diseases, especially prolactinoma. Six cross-sectional studies have been published recently, of which five studies do not show an association between the treatment of prolactinoma with cabergoline during 45-79 months and clinically relevant valvular regurgitation in a total of 413 patients. Nonetheless, concern is raised because the use of cabergoline was associated in one study with an increased prevalence of moderate tricuspid regurgitation, and in two other studies with mild tricuspid regurgitation. Furthermore, the use of cabergoline was associated with increased frequencies of valvular thickening, calcifications and increased mitral tenting area. At present, the clinical relevance of these findings is still uncertain, but concern is raised with respect to the safety of the use of cabergoline in the long-term treatment of prolactinomas. Echocardiographic evaluation should be considered in patients, who require long-term treatment with cabergoline, especially in high doses. There is a need for larger, preferably prospective, studies with careful echocardiographic assessment and with longer durations of follow-up than the currently available studies.

Section: Introductionmentioning

confidence: 99%

Cabergoline and cardiac valve disease in prolactinoma patients: additional studies during long-term treatment are required

Kars

Pereira²,

Bax³

et al. 2008

“…A recent nested case-control study (12) has shown in a large series that treatment with DA is associated with an increased risk of clinically relevant valve disease (CRVD) in PD but not in hyperprolactinemic patients. Over the past 5 years, 15 independent studies (13,14,15,16,17,18,19,20,21,22,23,24,25,26,27) (Table 1) have investigated the effects of CAB on the development of CRVD in patients with prolactinomas. Overall, these studies have reported a median CRVD rate of w4%, with the prevalence of CRVD ranging from 54% (13), 40% (24), 15% (17) to 0% (15,16,19,21) and valvulopathy being assessed according to the International Guidelines suggested by the American Society of Echocardiography (28,29) in all studies and also according to the European Association of Echocardiography (30,31) in ten studies (13,16,17,18,20,22,23,25,26,27).…”

Section: Introductionmentioning

confidence: 99%

Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas

Auriemma¹,

Pivonello

Perone

et al. 2013

Objective: Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia. Subjects and methods: Forty patients (11 men and 29 women, aged 38.7G12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48-1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography. Results: At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (PZ0.78) and pulmonic (PZ0.89) regurgitations and of mild aortic (PZ0.89) and tricuspid (PZ0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; PZ0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one. Conclusion: CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.

“…Cabergoline, which possesses a complete 5HT 2b agonistic activity, is the drug of choice in the treatment of prolactinomas, but the results of observational studies investigating the risk of FVHD in these patients are still controversial. Some of them have reported no relevant findings (8,9,10,11,12), five trials have observed clinically insignificant valvular changes (13,14,15,16,17), and only one study has reported an increased prevalence of moderate tricuspid regurgitation with a cumulative dose-dependent risk (18). Published data on the potential profibrotic effect of bromocriptine, a partial 5HT 2b agonist, are exclusively limited (19).…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor β1 is not a reliable biomarker for valvular fibrosis but could be a potential serum marker for invasiveness of prolactinomas (pilot study)

Еленкова¹,

Atanassova²,

Кirilov³

et al. 2013

Background: Transforming growth factor b1 (TGFb1) signaling pathway is crucial for both human fibrogenesis and tumorigenesis. Objective: This study aimed to investigate the usefulness of TGFb1 and matrix metalloproteinase 2 (MMP2) as potential circulating markers for fibrotic valvular heart disease (FVHD) and invasiveness as well as of Fetuin A as a marker for calcification in patients with prolactinomas. Design: The study population consisted of 147 subjects divided into four groups: 30 dopamine agonist (DA)-treated prolactinoma patients with proven FVHD and three control groups with normal echocardiograms: 43 DA-treated patients, 26 naïve patients, and 48 healthy subjects. Results: We observed significantly higher serum TGFb1 levels in all three patient groups than in the healthy subjects (21.4G8.86 vs 19.1G9.03 vs 20.7G11.5 vs 15.8G7.2 ng/ml; PZ0.032). Moreover, TGFb1 levels were significantly higher in patients with macroprolactinomas and invasive prolactinomas than in those with microprolactinomas and noninvasive tumors respectively. In addition, a strong positive linear relationship between TGFb1 levels and invasiveness score (rZ0.924; P!0.001) and a moderate correlation between TGFb1 levels and tumor volume (rZ0.546; P!0.002) were observed in patients with invasive prolactinomas. By contrast, prolactin (PRL) levels exhibited a better correlation with tumor volume (rZ0.721; P!0.001) than with invasiveness score (rZ0.436; P!0.020). No significant difference was observed in Fetuin A levels between patients with FVHD and healthy controls. Results concerning MMP2 were unclear. Conclusions: TGFb1, MMP2, and Fetuin A are not reliable biomarkers for valvular fibrosis and calcification in DA-treated patients with prolactinomas, but TGFb1 may represent a useful serum marker for tumor invasiveness. The simultaneous determination of TGFb1 and PRL levels could improve the noninvasive assessment of prolactinoma behavior.