Influence of hormonal functional status on survival in adrenocortical carcinoma: systematic review and meta-analysis

in European Journal of Endocrinology
Correspondence should be addressed to O M Dekkers; Email: o.m.dekkers@lumc.nl
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Objective

Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis. Many publications in ACC report on risk factors for a poor outcome; one risk factor studied is hormonal hypersecretion (cortisol, sex-hormones, steroid precursors or aldosterone). The aim of this systematic review was to study the association between hormonal secretion and recurrence or mortality in ACC.

Design

Systematic review and meta-analysis. We searched PubMed, EMBASE and The Cochrane library (January 2018) for cohort studies examining the association between hormonal secretion on overall or recurrence-free survival in ACC.

Methods

A random-effects model meta-analysis was performed to obtain a weighted relative risk comparing cortisol-secreting and/or androgen-secreting ACCs to non-secreting tumours regarding overall and recurrence-free survival. Risk of bias assessment was performed for all studies included.

Results

Nineteen publications were included representing a total of 3814 patients. Most studies were generally considered low/intermediate risk of bias. Meta-analysis showed higher mortality risk for cortisol-secreting ACCs, weighted relative risk 1.71 (95% CI: 1.18–2.47) combining studies that adjusted for tumour stage; also a higher recurrence risk was found for cortisol producing ACCs, relative risk 1.43 (95% CI: 1.18–1.73). Androgen secretion was not clearly associated with survival (RR: 0.82, 95% CI: 0.60–1.12).

Conclusion

This systematic review and meta-analysis show that cortisol-secreting ACCs are associated with a worse overall survival; future research is needed to establish whether this association points to negative effects of cortisol action, whether it signifies a more aggressive ACC subtype or whether cortisol is merely a prognostic marker.

Downloadable materials

  • Appendix 1: Pubmed/Embase/Cochrane search
  • Appendix 2: Study characteristics of included publications
  • Appendix 3: Risk of bias assessment of individual publication. The colours represent the following: green = low risk of bias; orange = intermediate risk of bias; red = high risk of bias. Numbers correspond to numbers of the articles in appendix 2.
  • Appendix 4: Funnel plot of publications on mortality in cortisol secreting ACCs
  • Appendix 5: Funnel plot of publications on mortality in functional ACCs
  • Appendix 6: Relative risk of functional ACC for overall survival
  • Appendix 7: relative risk of functional ACC for recurrence-free survival
  • Appendix 8: Relative risk of androgen secretion for overall survival
  • Appendix 9: Meta-regression analysis

 

     European Society of Endocrinology

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    Search strategy.

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    Weighted relative risks of hormone-secreting ACCs for overall survival.

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    Weighted relative risk of cortisol-secreting ACCs for overall survival.

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    Weighted relative risk of cortisol-secreting ACCs for recurrence-free survival.

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