Asymmetric Adrenals: Sexual Dimorphism of Adrenal Tumors

Abstract

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 characterized the influence of sex and adrenal asymmetry on the emergence of adrenal tumors. Methods We conducted a multicenter, observational study involving 8037 patients with adrenal tumors, including adrenocortical carcinoma (ACC), aldosterone-producing adenoma (APA), cortisol-secreting adrenocortical adenomas (CSAs), non-aldosterone-producing adrenal cortical adenoma (NAPACA), pheochromocytoma (PCC), and neuroblastoma (NB), and investigated tumor lateralization according to sex. Human adrenal tissues (n = 20) were analyzed with a multiomics 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 PCC (n = 1824) were more common in females than in males (female-to-male ratio: 1.1:1-3.8:1), whereas NBs (n = 2320) and APAs (n = 228) were less prevalent in females (0.8:1). ACC, APA, CSA, NAPACA, and NB occurred more frequently in the left than in the right adrenal (left-to-right ratio: 1.1:1-1.8:1), whereas PCC 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; females have smaller adrenals than males. Conclusion Adrenal asymmetry in both sexes may be related to the pathogenesis of adrenal tumors and should be considered during the diagnosis of these tumors.

Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma

“…Similar to our study on sex differences in adrenal diseases [ 7 ], we found a higher percentage of females with PPGL in European compared to Asian patients. Additionally, the European cohort contained a much higher fraction of HNPs and germline cluster 1A genes than the Asian one.…”

“…Nevertheless, female sex in Europe was significantly associated with cluster 2 and not cluster 1A gene PVs. The reason for the higher number of female patients with PPGL in Europe is unknown, but it appears to be a more general phenomenon that occurs across PCC [ 7 ] and HNP [ 78 ] but not PGL as our analysis showed. Behavioral or environmental factors might play a role but have not been studied in PPGL.…”

“…The observed alterations were distinct between cancer types. Recently, we demonstrated that both sexes have different susceptibilities to the occurrence of adrenal tumors [ 7 ].…”