Adrenal Cortisol Hyper-Responsiveness as a Possible Cause of Obesity, Insulin Resistance and Cardiovascular Risk

Introduction: Increased cortisol concentrations due to endogenous over-secretion or exogenous administration result in obesity, insulin resistance, and increased risk of cardiovascular disease (CVD). We wanted to assess whether non pathological adrenal hyper responsiveness to ACTH could reproduce these changes and thus explain how stress, via the pituitary-adrenal axis, can also cause such abnormalities. Methods: ACTH stimulation test was performed on 1072 non diabetic healthy participants in the St. Francis Heart Study and multiple blood tests, anthropometric measurements and coronary calcium scores were also obtained. Results: Post stimulation cortisol concentrations were correlated with obesity, insulin resistance, lipid abnormalities, Framingham scores (all p ≤ 0.01), but not with blood pressure and not with coronary calcium scores. In multivariate models, increased cortisol secretion was significantly predictive of abdominal fat even after controlling for insulin resistance, and of insulin resistance even after controlling for abdominal fat. Conclusions: Adrenal hyper responsiveness may explain some of the observation of the relationship between stress and the metabolic abnormalities which can lead to CVD. Increased cortisol secretion predicts insulin resistance and obesity , independently of each other.