Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome

Abstract

The mechanisms by which glucocorticoids regulate food intake and resulting body mass in humans are not well-understood. One potential mechanism could involve modulation of reward processing, but human stress models examining effects of glucocorticoids on behavior contain important confounds. Here, we studied individuals with Cushing's syndrome, a rare endocrine disorder characterized by chronic excess endogenous glucocorticoids. Twenty-three patients with Cushing's syndrome (13 with active disease; 10 with disease in remission) and 15 controls with a comparably high body mass index (BMI) completed two simulated food-choice tasks (one with “explicit” task contingencies and one with “probabilistic” task contingencies), during which they indicated their objective preference for viewing high calorie food images vs. standardized pleasant, unpleasant, and neutral images. All participants also completed measures of food craving, and approximately half of the participants provided 24-h urine samples for assessment of cortisol and cortisone concentrations. Results showed that on the explicit task (but not the probabilistic task), participants with active Cushing's syndrome made fewer food-related choices than participants with Cushing's syndrome in remission, who in turn made fewer food-related choices than overweight controls. Corroborating this group effect, higher urine cortisone was negatively correlated with food-related choice in the subsample of all participants for whom these data were available. On the probabilistic task, despite a lack of group differences, higher food-related choice correlated with higher state and trait food craving in active Cushing's patients. Taken together, relative to overweight controls, Cushing's patients, particularly those with active disease, displayed a reduced vigor of responding for food rewards that was presumably attributable to glucocorticoid abnormalities. Beyond Cushing's, these results may have relevance for elucidating glucocorticoid contributions to food-seeking behavior, enhancing mechanistic understanding of weight fluctuations associated with oral glucocorticoid therapy and/or chronic stress, and informing the neurobiology of neuropsychiatric conditions marked by abnormal cortisol dynamics (e.g., major depression, Alzheimer's disease).

Patients with hypercortisolemic Cushing disease possess a distinct class of hematopoietic progenitor cells leading to erythrocytosis

“…Cortisol Levels. Twenty-four hour Urinary Free Cortisol (UFC) and serum cortisol levels were quantified by gas chromatography-mass spectroscopy as described 12 . The limit of sensitivity of this assay is 2ng with inter-assay coefficients of variations <10%.…”

Genome-Wide Association Study of Dietary Pattern Scores

“…Glucocorticoids (GCs) are known to mobilize the endocannabinoid system which is essential for negative feedback regulation of the hypothalamic–pituitary–adrenal axis [ 63 ]. In addition, a recent study using Cushing’s syndrome patients as a unique model of chronic GCs exposure demonstrated a negative correlation of urine cortisone with food-related choice thus implying a potential role of GR in food-choice behavior [ 64 ]. STAT family members and PDX1 TF were found to be overrepresented from SNP-surrounding sequences from both Prudent and Western reported dietary pattern-associated SNPs ( Tables S5 and S6 ).…”

Neuroimaging and neuroendocrine insights into food cravings and appetite interventions in obesity

“…Notably, 60% of obese women with PCOS were categorized with binge eating behaviors, and multivariate regression revealed factors including total food cravings, emotional eating scores, and BMI as significant predictors of binge-eating symptom scores in PCOS patients (Jeanes et al ., 2017 ). Whereas in Cushing's Syndrome, abnormal glucocorticoid levels might be driving changed food-reward responses (Moeller et al ., 2016 ). The research compared the appetite symptoms of type 2 diabetes mellitus (T2DM) patients with non-diabetic controls.…”

“…In conclusion, food cravings, distinct from appetite, are shaped by individual preferences and are intricately tied to one's psychological state. A holistic exploration of this subject, incorporating factors such as ghrelin, leptin, and various neuro-endocrine mechanisms, is paramount (Krishnan et al ., 2016 ) (Parker et al ., 2021 ) (Moeller et al ., 2016 ). As we venture further, incorporating both the biological and behavioral intricacies of this phenomenon into interventions will be vital.…”