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

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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 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.

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.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

CD:

Cushing’s disease

CI:

Confidence interval

CS:

Cushing’s syndrome

D2R:

Type 2 dopamine receptor

DM:

Diabetes mellitus

DR:

Dopamine receptor

IPD:

Individual participant data

IQR:

Interquartile range

OR:

Odds ratio

SD:

Standard deviation

TSS:

Transsphenoidal surgery

UFC:

Urinary free cortisol

UNL:

Upper normal limit

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Endocrinology, JIPMER, Fourth Floor, Superspecialty Block, Puducherry, 605006, India

    R. Palui, J. Sahoo, S. Kamalanathan & H. Durgia

  2. Department of Preventive and Social Medicine, JIPMER, Puducherry, India

    S. S. Kar

  3. Department of Clinical Pharmacology, JIPMER, Puducherry, India

    S. Selvarajan

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  1. R. Palui
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Contributions

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.

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Correspondence to J. Sahoo.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Palui, R., Sahoo, J., Kamalanathan, S. et al. Effect of cabergoline monotherapy in Cushing’s disease: an individual participant data meta-analysis. J Endocrinol Invest 41, 1445–1455 (2018). https://doi.org/10.1007/s40618-018-0936-7

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