Effect of cabergoline monotherapy in Cushing’s disease: an individual participant data meta-analysis
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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.
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.
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 CD with cabergoline monotherapy was 39.4% (95% confidence interval 0.31–0.49; P = 0.026). 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.
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.
KeywordsCabergoline Cushing’s disease Dopamine agonist Remission Urinary free cortisol
Type 2 dopamine receptor
Individual participant data
Urinary free cortisol
Upper normal limit
We sincerely thank Dr. A Tabarin, Dr. A Ferriere and Dr. Pia Burman for responding to our queries and sharing their patients’ data with us.
JS and RP were involved in each of the following points: (1) design, (2) data collection, (3) analysis, and (4) writing manuscript. SS and HD were involved in each of the following points: (1) data collection, (2) quality assessment of articles, (3) analysis, and (4) reviewing manuscript. SSK was involved in each of the following points: (1) design, (2) analysis, (3) quality assessment of studies, and (4) reviewing manuscript. SK was involved in each of the following points: (1) design, (2) data collection, and (3) reviewing manuscript. All the authors approved the final version of this manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
For this type of study, informed consent was not necessary.
- 6.Carolina Di Somma, Rosario Pivonello, Sandro Loche et al (2002) Severe impairment of bone mass and turnover in Cushing’s disease: comparison between childhood-onset and adulthood-onset disease. Clin Endocrinol (Oxf) 56:153–158. https://doi.org/10.1046/j.0300-0664.2001.01454.doc.x CrossRefGoogle Scholar
- 11.Patil CG, Veeravagu A, Prevedello DM et al (2008) Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery 63:266–271. https://doi.org/10.1227/01.neu.0000313117.35824.9f CrossRefPubMedGoogle Scholar
- 17.Pivonello R, De Martino MC, Cappabianca P et al (2009) The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab 94:223–230. https://doi.org/10.1210/jc.2008-1533 CrossRefPubMedGoogle Scholar
- 25.http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018089806. Accessed 9 Mar 2018
- 28.Phan K, Tian DH, Cao C et al (2015) Systematic review and meta-analysis: techniques and a guide for the academic surgeon. Ann Cardiothorac Surg 4:112–122. https://doi.org/10.3978/j.issn.2225-319X.2015.02.04 CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Lamberts SWJ, Lange SAD, Stefanko SZ (1982) Adrenocorticotropin-secreting pituitary adenomas originate from the anterior or the intermediate lobe in cushing’s disease: differences in the regulation of hormone secretion. J Clin Endocrinol Metab 54:286–291. https://doi.org/10.1210/jcem-54-2-286 CrossRefPubMedGoogle Scholar
- 46.van der Pas R, Feelders RA, Gatto F et al (2013) Preoperative normalization of cortisol levels in Cushing’s disease after medical treatment: consequences for somatostatin and dopamine receptor subtype expression and in vitro response to somatostatin analogs and dopamine agonists. J Clin Endocrinol Metab 98:E1880–1890. https://doi.org/10.1210/jc.2013-1987 CrossRefPubMedGoogle Scholar
- 49.Schopohl J, Gu F, Rubens R et al (2015) Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing’s disease: results from an open-ended, open-label extension trial. Pituitary 18:604–612. https://doi.org/10.1007/s11102-014-0618-1 CrossRefPubMedGoogle Scholar