Sex Differences in Hypercortisolism and Glucose-Metabolism Disturbances in Patients with Mild Autonomous Cortisol Secretion: Findings From a Single Center in China

Abstract

Background and objectiveMild autonomous cortisol secretion (MACS) presents with a marked female preponderance, but whether the sex difference in its distribution has any relevance to the presentation and outcome of the disease is unknown. The aim of this study was therefore to compare biochemical indices of hypercortisolism and impaired glucose metabolism between male and female patients with MACS.MethodWe enrolled a total of 98 patients with autonomous/possible autonomous cortisol secretion in our study, and indices of hypercortisolism and glucose metabolism were collected and compared between the male and female patients. Logistic regression models were used to evaluate the association between sex and cortisol-secretory ability, as well as between the latter and glucose metabolism. In addition, we conducted further stratified analyses according to the degree of autonomous cortisol secretion and menopausal status.ResultsCortisol levels at 00:00 and 08:00 h after a 1-mg dexamethasone suppression test (DST) and low-dose DST were significantly higher in female than in male MACS patients, and the inhibition rate of 1-mg DST was lower in the women than in the men. This significant difference still remained after adjusting for age, BMI, and the course of the disease. Logistic regression analysis revealed a significant association between autonomous cortisol secretion and fasting C-peptide, as well as with the C-peptide-to-glucose ratio in females relative to male patients. In addition, stratified analyses indicated that this association was observed only among women with autonomous cortisol secretion and who were premenopausal.ConclusionThe level of autonomic cortisol secretion in female patients with MACS was higher than in male patients, and the association between autonomous cortisol secretory ability and glucose homeostasis was only noted in patients with autonomous cortisol secretion and in premenopausal women. This phenomenon will, however, require closer follow-up.

Are comorbidities of patients with adrenal incidentaloma tied to sex?

“…This finding is in line with the results of a recent cross-sectional large multicenter study including 4374 patients with AI, which showed a significant increase of all-cause mortality and major adverse cardiovascular event (MACE) in female patients younger than 65 years with autonomous cortisol secretion ( 9 ). Moreover, a monocentric study including 98 patients with MACS reported only in premenopausal women a direct correlation between autonomous cortisol secretion levels and levels of fasting C-peptide or fasting C-peptide-to-glucose ratio, which are considered indexes of insulin resistance ( 41 ).…”

A method for evaluating the risks of glucose dysregulation in daily life by continuous measurement of glucose excursions under reduced glycemic load: a pilot study

“…One is highlighted by the existence of individuals showing null effects of AGI on reducing their glucose excursions. Causes of elevated glucose levels include stress hormones associated with not only insulindependent endocrine systems but also the central nervous system, such as cortisol (Ortiz et al, 2019;Bentele et al, 2021;Ouyang et al, 2022). Further studies are needed to explore the mechanism by which glycemic dysregulation occurs in such individuals.…”