Association between contralateral adrenal and hypothalamus-pituitary-adrenal axis in benign adrenocortical tumors

Hongyuan Zhu; Luming Wu; Tingwei Su; Lei Jiang; Weiwei Zhou; Yiran Jiang; Cui Zhang; Xu Zhong; Weiqing Wang

doi:10.3389/fendo.2023.1199875

Association between contralateral adrenal and hypothalamus-pituitary-adrenal axis in benign adrenocortical tumors

Front Endocrinol (Lausanne). 2023 Jul 25:14:1199875. doi: 10.3389/fendo.2023.1199875. eCollection 2023.

Authors

Hongyuan Zhu¹, Luming Wu¹, Tingwei Su¹, Lei Jiang¹, Weiwei Zhou¹, Yiran Jiang¹, Cui Zhang¹, Xu Zhong¹, Weiqing Wang^{1

2}

Affiliations

¹ Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Jiaotong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Abstract

Context: Adrenal incidentaloma (AI) is commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion is the most common functional disorder detected in AI.

Objective: To delineate the association between radiological characteristics of benign adrenocortical tumors and hypothalamus-pituitary-adrenal (HPA) axis.

Methods: In the study, 494 patients diagnosed with benign unilateral adrenocortical tumors were included. Mild autonomous cortisol secretion (MACS) was diagnosed when cortisol after 1mg-dexamethasone suppression test (1-mg DST) was in the range of 1.8-5ug/dl. Non-functional adrenocortical tumor (NFAT) was diagnosed as cortisol following 1-mg DST less than 1.8ug/dL. We performed Logistics regression and causal mediation analyses, looking for associations between radiological characteristics and the HPA axis.

Results: Of 494 patients, 352 (71.3%) with NFAT and 142 (28.7%) with MACS were included. Patients with MACS had a higher tumor diameter, thinner contralateral adrenal gland, and lower plasma ACTH and serum DHEAS than those with NFAT. ACTH (OR 0.978, 0.962-0.993) and tumor diameter (OR 1.857, 95%CI, 1.357-2.540) were independent factors associated with decreased serum DHEAS (all P<0.05). ACTH was also associated with decreased contralateral adrenal diameter significantly (OR 0.973, 95%CI, 0.957-0.988, P=0.001). Causal mediation analysis showed ACTH mediated the effect significantly for the association between 1-mg DST results and DHEAS level (P_mediation<0.001, proportion=22.3%). Meanwhile, we found ACTH mediated 39.7% of the effects of 1-mg DST on contralateral adrenal diameter (P_mediation=0.012).

Conclusions: Patients with MACS had thinner contralateral adrenal glands and disturbed HPA axes compared with NFAT. ACTH may partially be involved in mediating the mild autonomous cortisol secretion to DHEAS and the contralateral adrenal gland.

Keywords: causal mediation analysis; contralateral adrenal; hypothalamus-pituitary-adrenal (HPA) axis; mild autonomous cortisol secretion; nonfunctional adrenocortical tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Neoplasms* / diagnosis
Adrenocortical Adenoma*
Adrenocorticotropic Hormone
Dehydroepiandrosterone
Dehydroepiandrosterone Sulfate
Humans
Hydrocortisone
Hypothalamo-Hypophyseal System
Pituitary-Adrenal System

Substances

Hydrocortisone
Dehydroepiandrosterone
Dehydroepiandrosterone Sulfate
Adrenocorticotropic Hormone

Supplementary concepts

Adrenal incidentaloma

Grants and funding

This work was supported by the National Key Research and Development Program of China (2021YFC2501600, 2021YFC2501603); the Shanghai Shenkang Hospital Development Center (SHDC2020CR2002A and SHDC2020CR6015); Natural Science Foundation of Shanghai (22ZR1439100); and National Natural Science Foundation of China (82170797).