Glucocorticoid metabolism and the Metabolic Syndrome: Associations in an elderly cohort

Objective: The phenotype of the Metabolic Syndrome (hypertension, insulin resistance and hyperlipidaemia) bears similarities to Cushing's Syndrome, in which the cause of these features is elevated cortisol production. We have investigated relationships between glucocorticoid production and features of the Metabolic Syndrome in a cohort of elderly subjects. Design: A cross-sectional analysis was carried out of a subset of a birthweight cohort from Sheffield. Methods: 92 men and 40 women (aged 69-75 y) representative of the original cohort were investigated. Features of the Metabolic Syndrome (blood pressure, BMI, waist hip ratio, fasting glucose, insulin and triglycerides) were recorded and urinary glucocorticoid metabolites were measured by gas chromatography mass spectrometry. Results: Total glucocorticoid metabolites were correlated with the overall phenotype of the Metabolic Syndrome (P=0.002), whereas specific pathways of metabolism (activity of 11beta-hydroxysteroid dehydrogenases and A-ring reductases) did not show significant associations. Specifically total glucocorticoid production increased with increasing systolic blood pressure (r= 0.21, P=0.013), fasting glucose (r=0.19, P=0.02) and insulin (r= 0.23, P=0.025). Glucocorticoid production was greater with increasing abdominal girth (r=0.19, P=0.033), but there was no association with enhanced metabolism via a specific pathway. Within this cohort, birthweight was not associated with total glucocorticoid metabolites. However, decreasing birthweight (P =0.022), increasing obesity (P=0.026) and increasing total glucocorticoid production (P=0.009) were all independent predictors of fasting glucose. Conclusions: These data support the concept that cortisol production is enhanced in the Metabolic Syndrome, although they did not confirm the recent evidence that increased cortisol secretion is predicted by low birthweight.