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Global Cushing’s disease epidemiology: a systematic review and meta-analysis of observational studies

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Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Cushing’s disease (CD), 70% of endogenous hypercortisolism cases, is a rare disease caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. To date, no systematic reviews and meta-analyses on its global epidemiology have been published. We provide a systematic review and meta-analysis of CD global epidemiology, also evaluating the quality of study reporting for the identified studies.

Methods

MEDLINE and EMBASE databases were searched for studies on CD epidemiology from inception until November 30th, 2020, including original observational studies in English about CD prevalence and/or incidence for well-defined geographic areas. Two reviewers independently extracted data and assessed reporting quality. CD prevalence/incidence pooled estimates were derived from a random-effects meta-analysis. Reporting quality was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases, heterogeneity using the Cochran’s Q-test and its derived measure of inconsistency (I2).

Results

Thirteen studies were included. The pooled CD prevalence was 2.2 [95% CI 1.1–4.8] per 100,000, while the incidence rate was 0.24 [95% CI 0.15–0.33] per 100,000 person-years. For both parameters, considerable between-studies heterogeneity was found (I2 = 78.8% and 87.8%, respectively). The quality of study reporting was rated as medium for 11 (84.6%) studies and as low for 2 (15.4%).

Conclusion

Overall, our systematic meta-analysis demonstrated CD epidemiology to be similarly reported across different areas of the world, with some exceptions regarding regional differences or observation period intervals. Keeping into account the methodological differences between each paper, large-scale studies on CD epidemiology are warranted. Setting up national specific registries, based on standardized diagnostic and clinical parameters, with clearly defined selection and analysis criteria, and a strong cooperation between the scientific national societies for endocrinology is crucial to exclude other causes of variability (i.e. geographical differences due to other factors like (epi)genetic changes), and to support public health decision making.

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Funding

This study was conducted in the context of the Progetto di Ricerca di Interesse Nazionale (PRIN) 2017 “IN Search of early clinical and molecular Predictors of diagnosis and treatment response In patients with Rare Endocrine disorders: the INSPIRE project”, which received a grant from the Italian Ministry of Education, University and Research (2017N8CK4K), and of the project PRIN 2017 “Identification of new biomarkers and clinical determinants for management improvement of patients with pituitary tumor related syndromes”, which received a grant from the Italian Ministry of Education, University and Research (2017S55RXB).

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Author notes

  1. G. Giuffrida and S. Crisafulli: equal contribution as first authors.

  2. S. Cannavò and G. Trifirò: equal contribution as senior authors.

Authors and Affiliations

  1. Department of Human Pathology of Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy

    G. Giuffrida, F. Ferraù, M. Ragonese & S. Cannavò

  2. Department of Medicine, University of Verona, Verona, Italy

    S. Crisafulli

  3. Endocrine Unit, University Hospital “G. Martino”, Messina, Italy

    F. Ferraù, Y. Alessi & S. Cannavò

  4. Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    A. Fontana

  5. Department of Chemical, Biological, Pharmaceutical, Environmental Sciences, University of Messina, Messina, Italy

    F. Calapai

  6. Department of Diagnostics and Public Health, University of Verona, Verona, Italy

    N. Luxi & G. Trifirò

Authors
  1. G. Giuffrida
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  2. S. Crisafulli
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  3. F. Ferraù
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  4. A. Fontana
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  5. Y. Alessi
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  6. F. Calapai
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  7. M. Ragonese
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  8. N. Luxi
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  9. S. Cannavò
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  10. G. Trifirò
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Corresponding author

Correspondence to F. Ferraù.

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Conflict of interest

Dr. Francesco Ferraù, MD, PhD, is a member of the Journal Editorial board. The authors declare that they have no other conflict of interest that could be perceived as prejudicing the impartiality of the research reported. Due to the nature of the study, neither informed consent by patients nor approval by the local Ethics Committee was required.

Research involving human participants and/or animals

This study is a metanalysis of epidemiological studies, so no animals have been involved.

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No consent has been required to perform the study.

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Giuffrida, G., Crisafulli, S., Ferraù, F. et al. Global Cushing’s disease epidemiology: a systematic review and meta-analysis of observational studies. J Endocrinol Invest 45, 1235–1246 (2022). https://doi.org/10.1007/s40618-022-01754-1

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  • DOI: https://doi.org/10.1007/s40618-022-01754-1

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