Suntornlohanakul Onnicha, Ronchi Cristina L, Arlt Wiebke, Prete Alessandro
Endocrinology and Metabolism Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Department of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham B152TT, United Kingdom.
Eur J Endocrinol. 2025 Apr 30;192(5):R1-R12. doi: 10.1093/ejendo/lvaf088.
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.
良性肾上腺皮质肿瘤是最常见的肾上腺肿瘤。过去几十年的证据凸显了其在患病率、临床特征和治疗结果方面的性别差异。导致库欣综合征的分泌皮质醇腺瘤，特别是那些具有与更严重表型相关的PRKACA或GNAS体细胞突变的腺瘤，或轻度自主性皮质醇分泌（MACS），在女性中更为常见。这种性别二态性的潜在机制仍有待充分阐明。对小鼠的研究揭示了雄激素在雄性中的保护作用，导致肾上腺皮质细胞生长速率减慢。此外，来自人类肾上腺肿瘤组织的证据表明，肾上腺皮质中的雌激素、孕激素和促黄体生成素/绒毛膜促性腺激素信号可能在肾上腺肿瘤发生和类固醇生成中起作用。在临床上，青春期、孕期和更年期期间分泌皮质醇的肾上腺皮质腺瘤或结节性增生发病率增加支持了这一点。值得注意的是，患有MACS的女性似乎更容易受到皮质醇过量有害影响，且死亡率风险高于男性。分泌醛固酮腺瘤的女性体细胞KCNJ5突变的患病率高于男性，携带这些突变的患者肾上腺切除术后可能有更良好的临床结果。在本综述中，我们总结了良性肾上腺皮质肿瘤性别二态性背后的可能机制，并提供了其在患病率、临床表现和结果方面性别特异性差异的最新概述，重点关注皮质醇和醛固酮过多。考虑到性别二态性对于指导诊断和管理以及为这些患者提供优化护理的咨询至关重要。
