J Clin Endocrinol Metab. 2024 Jan 18;109(2):471-482. doi: 10.1210/clinem/dgad515

Asymmetric Adrenals: Sexual Dimorphism of Adrenal Tumors

Nicole Bechmann1, Mats Leif Moskopp2, Georgiana Constantinescu3, Anthony Stell4, Angela Ernst5, Frank Berthold6, Frank Westermann7,8, Jingjing Jiang9, Longfei Lui10, Elisabeth Nowak11, Stephanie Zopp11, Karel Pacak12, Mirko Peitzsch1, Andreas Schedl13, Martin Reincke11, Felix Beuschlein11,14,15, Stefan R Bornstein3, Martin Fassnacht16, Graeme Eisenhofer3

1Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
2Department of Neurosurgery, Vivantes Friedrichshain Hospital, Charité Academic Teaching Hospital, 10249 Berlin, Germany.
3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany. School of Computing and Information Systems, University of Melbourne, 3052 Melbourne, Australia.
5Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany.
6Children’s Hospital, University of Cologne, 50735 Cologne, Germany.
7Hopp Children’s Cancer Center Heidelberg (KiTZ), 69120 Heidelberg, Germany.
8Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
9Department of Endocrinology and Metabolism, Zhongshan Hospital, 200031 Shanghai, China.
10Department of Urology, Xiangya Hospital, Central South University, 410017 Changsha, China.
11Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, 80539 Munich, Germany.
12Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD 20892, USA.
13Université Côte d’Azur, Inserm, CNRS, Institut de Biologie Valrose, 06108 Nice, France.
14Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Zurich, Switzerland.
15Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland.
16Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital of Würzburg, University of Würzburg, 97080 Würzburg, Germany.


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.

DOI: 10.1210/clinem/dgad515