Effect of cabergoline monotherapy in Cushing's disease: an individual participant data meta-analysis

Abstract

Context: The primary treatment of choice for Cushing's disease (CD) is the removal of the pituitary adenoma by transsphenoidal surgery (TSS). The surgical failure is seen in up to 75% of cases depending on the experience of the surgeon in different studies. Medical therapy is one of the options for the treatment of recurrent or persistent CD.

Methodology: The primary outcome of this meta-analysis was to find the proportion of patients achieving normalisation of 24-h urinary free cortisol (remission of CD) following cabergoline monotherapy. Literature search was conducted in January 2018 in PubMed/MEDLINE database from its date of inception to 31st December 2017. The search strategy used was "[(cushing) OR Cushing's] AND cabergoline". Individual participant data were extracted from the included studies and risk of bias was analysed by review checklist proposed by MOOSE.

Results: The individual participant data of 124 patients from six observational studies were included in this meta-analysis. 92 patients (74.2%) had past pituitary surgery. The proportion of patients achieving remission of Cushing’s disease (CD) with cabergoline monotherapy was 34% (95% confidence interval 0.26–0.43; P = 0.001) [corrected]. The previous surgery [odds ratio (OR) 28.4], duration of cabergoline monotherapy (OR 1.31) and maximum cabergoline dose (OR 0.19) were predictors for remission of CD. Mild and severe side effects were reported in 37.3% and 5.6% of patients, respectively, during cabergoline monotherapy.

Conclusions: This meta-analysis shows that cabergoline monotherapy is a reasonable alternative for subjects with persistent or recurrent CD after TSS. It can also be used in CD patients either as a bridge therapy while waiting for surgery or in those unwilling for surgery or have contraindication to it.

Keywords: Cabergoline; Cushing’s disease; Dopamine agonist; Remission; Urinary free cortisol.