Serum dexamethasone levels do not correlate with cortisol and body mass index of patients in the low dose dexamethasone suppression test

Objectives: The low dose dexamethasone suppression test (LDDST) is routinely used in establishing the diagnosis of Cushing's syndrome. However, factors such as variable resorption of dexamethasone and an increased metabolism could lead to false positive results, particularly in obese patients. The aim of our study was to evaluate a possible association between BMI and serum dexamethasone levels. Methods: Nocturnal blood withdrawals were performed in 10 adult subjects at 1, 3, 5, 7, 8 AM to evaluate the kinetic of dexamethasone. Furthermore, 51 patients were enrolled in a regular 2mg dexamethasone suppression test. Patients treated with liver enzyme modulating pharmaceuticals (carbamazepine, phenobarbitale, phenytoin and others) were excluded from this study. Dexamethasone was determined in serum at start and end of the LDDST by an in-house immunoassay Results: In the kinetic study maximal dexamethasone concentration was measured at approximately 3 AM. At 8 AM, median of dexamethasone was reduced to 73.4%. In the LDDST dexamethasone levels were non-detectable at start and demonstrated a high variation at 8 AM, that was inversely correlated with BMI (r=-0.27, p=0.057). Cortisol concentrations, measured at the same time, were neither correlated with dexamethasone nor with BMI values. Furthermore, dexamethasone levels determined in patients with a BMI below 30kg/m 2 (n=21) were not significantly different from values of obese patients with a BMI higher than 30kg/m 2 (n=31, p>0.05). Conclusion: In the LDDST BMI of individual patients could modulate the resorption rate of dexamethasone but appears to have no impact on cortisol levels. This finding is supported by a lack of correlation between BMI and cortisol data. Therefore, obesity should not be a cause of falsely positive results in the LDDST. However, we cannot exclude that the observed variation in the pharmacokinetics of dexamethasone influences cortisol levels at 8 AM.