CONTEXT: Sexual dimorphism has direct consequences on the incidence and survival of cancer. Early and accurate diagnosis is crucial to improve prognosis.

OBJECTIVE: This work aimed to characterised the influence of sex and adrenal asymmetry on the emergence of adrenal tumours.

METHODS: We conducted a multicentre, observational study involving 8037 patients with adrenal tumours, including adrenocortical carcinoma (ACC), aldosterone-producing adenoma (APA), cortisol-secreting adrenocortical adenomas (CSAs), non-aldosterone producing adrenal cortical adenoma (NAPACA), phaeochromocytoma and neuroblastoma, and investigated tumour lateralisation according to sex. Human adrenal tissues (n=20) were analysed with a multi-omics approach that allows determination of gene expression, catecholamine and steroid contents in a single sample. In addition, we performed a literature review of computed tomography and magnetic resonance imaging-based studies examining adrenal gland size.

RESULTS: ACC (n=1858); CSA (n=68), NAPACA (n=2174) and phaeochromocytoma (n=1824) were more common in females than in males (female-to-male ratio: 1.1:1 - 3.8:1), while neuroblastomas (n=2320) and APAs (n=228) were less prevalent in females (0.8:1). ACC, APA, CSA, NAPACA and neuroblastoma occurred more frequently in the left than in the right adrenal (left-to-right ratio: 1.1:1-1.8:1), whereas phaeochromocytoma arose more often in the right than in the left adrenal (0.8:1). In both sexes, the left adrenal was larger than the right adrenal, whereby females have smaller adrenals than males.

CONCLUSION: Adrenal asymmetry in both sexes may be related to the pathogenesis of adrenal tumours and should be considered during the diagnosis of these tumours.