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Thomas Vanbrabant, Martin Fassnacht, Guillaume Assie and Olaf Dekkers

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.

Result Nineteen publications were included representing a total of 3,814 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 0.60-1.14).


This systematic review and meta-analysis shows 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.