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Background: 11 Beta-hydroxysteroid dehydrogenases (11HSDs) are enzymes involved in the interconversion of cortisol and cortisone. There are two isoenzymes of 11HSD, 11HSD1 and 11HSD2. A causative role of 11HSD, particularly 11HSD1, in metabolic syndrome is well established in experimental animals. However, its role in human metabolic syndrome is less clear. We examined the influence of global 11HSD activity on metabolic syndrome in the general population, using the circulating cortisol:cortisone ratio as an index of global 11HSD activity. Methods: A subsample of 269 sera randomly selected from the Thai National Health Examination Survey IV samples was analyzed for serum cortisol and cortisone levels by liquid chromatography-tandem mass spectrometry. Results: There was no association between serum cortisol and age. However, circulating cortisone was negatively correlated with age ( r  = -0.12, P  < 0.001), and the serum cortisol:cortisone ratio was positively associated with age ( r  = 0.03, P  < 0.001). No association was found between serum cortisol:cortisone ratio and body mass index (BMI) or serum lipids. Multivariate analyses showed that the serum cortisol:cortisone ratio was associated with high blood pressure ( P  < 0.05) independent of age, BMI, and sex. In subjects without hypertension, the serum cortisol to cortisone ratio was associated with mean systolic blood pressure after controlling for age, BMI, and sex. The cortisol:cortisone ratio was not significantly different between subjects with and without diabetes. After excluding the 16 subjects with diabetes, it was found that the serum cortisol:cortisone ratio was positively associated with fasting plasma glucose independent of age, BMI, and sex ( P  < 0.01). Conclusions: The global index of 11HSD activity, assessed by the circulating cortisol:cortisone ratio, was related to high blood pressure and fasting plasma glucose and may serve as a proxy to global 11HSD activity.