Sexual dimorphism in benign adrenocortical tumours
File(s)
Published version
Author(s)
Suntornlohanakul, Onnicha
Ronchi, Cristina L
Arlt, Wiebke
Prete, Alessandro
Type
Journal Article
Abstract
Benign adrenocortical tumours are the most common adrenal neoplasms. Evidence over the past few decades has highlighted sex differences in their prevalence, clinical characteristics, and treatment outcomes. Cortisol-producing adenomas causing either Cushing's syndrome, particularly those with PRKACA or GNAS somatic mutations associated with a more severe phenotype, or mild autonomous cortisol secretion (MACS) are more commonly observed in women. The mechanisms underpinning this sexual dimorphism remain to be fully elucidated. Studies in mice have revealed a protective role of androgens in males, leading to a decelerated growth rate of adrenocortical cells. Furthermore, evidence from human adrenal tumour tissue suggests that oestrogen, progesterone, and luteinising hormone/choriogonadotropin signalling in the adrenal cortex may play a role in adrenal tumourigenesis and steroid production. Clinically, this is supported by the increased incidence of cortisol-producing adrenocortical adenomas or nodular hyperplasia during puberty, pregnancy, and menopause. Notably, women with MACS seem to be more vulnerable to the harmful effects of cortisol excess and carry a higher mortality risk than men. Women with aldosterone-producing adenomas have a higher prevalence of somatic KCNJ5 mutations than men, and patients harbouring these mutations are likely to have more favourable clinical outcomes after adrenalectomy. In this review, we summarise the possible mechanisms behind the sexual dimorphism of benign adrenocortical tumours and provide an up-to-date overview of the sex-specific differences in their prevalence, clinical presentation, and outcomes, focusing on cortisol and aldosterone excess. Considering sexual dimorphism is crucial to guide diagnosis and management, and to counsel these patients for optimised care.
Date Issued
2025-05-01
Date Acceptance
2025-04-24
Citation
European Journal of Endocrinology (EJE), 2025, 192 (5), pp.R1-R12
ISSN
0804-4643
Publisher
Oxford University Press
Start Page
R1
End Page
R12
Journal / Book Title
European Journal of Endocrinology (EJE)
Volume
192
Issue
5
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40296186
PII: 8121447
Subjects
adrenal tumour
CHORIONIC-GONADOTROPIN
COMPUTED-TOMOGRAPHY
Cushing's syndrome
CUSHINGS-SYNDROME
Endocrinology & Metabolism
GENDER-DIFFERENCES
LH/HCG RECEPTORS
Life Sciences & Biomedicine
MACRONODULAR ADRENAL-HYPERPLASIA
MESSENGER-RIBONUCLEIC-ACID
mild autonomous cortisol secretion
PREDICTION SCORE
primary aldosteronism
PRIMARY ALDOSTERONISM
Science & Technology
sexual dimorphism
SOMATIC MUTATIONS
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-04-29