ACTH and cortisol dynamics after overnight dexamethasone suppression

The Endocrine society clinical practice guidelines recommend use of the 1-mg overnight dexamethasone suppression test (ONDST) to exclude autonomous cortisol excess and the cutoff suggested for exclusion of autonomous cortisol secretion in a post-dexamethasone sample is < 50 nmol/L (< 1.8 ug/dL). ONDST has a very high sensitivity of 98.6% and a specificity of 90.6%.  However, variable absorption and metabolism of dexamethasone by drugs causing induction/inhibition of hepatic clearance enzymes may affect the test results. False positive results were also noted in upto 50% of women taking oral contraceptive pills due to increased CBG levels. Certain psychiatric disorders like depression, anxiety disorder and obsessive-compulsive disorder are associated with mild hypercortisolism due to upregulated hypothalamic-pituitary-adrenal (HPA) axis which may cause abnormal dexamethasone suppressibility and produce false positive results. Outcome of ONDST may be affected by wide inter-individual variability in serum dexamethasone concentrations achieved after administration of 1 mg dexamethasone and hence concurrent serum dexamethasone levels     should be measured so that this information may be taken into consideration when interpreting ONDST results. Dexamethasone acts by direct suppression of hypothalamic-pituitary-adrenal (HPA) axis. The suppressed cortisol levels are due to the negative feedback of exogenous dexamethasone on the hypothalamic and pituitary glucocorticoid receptors which leads to decreased corticotropin releasing hormone (CRH) and adreno-corticotropic hormone (ACTH) production respectively. In theory, measuring ACTH levels rather than cortisol levels in the post-dexamethasone sample should more accurately reflect the intactness of the HPA axis regulation. Also, in conditions with alteration in CBG levels leading to falsely low or high total cortisol values, measuring ACTH after ONDST might better reflect dexamethasone suppressibility. Data showing ACTH and cortisol dynamics after ONDST is scarce in the existing literature. Hence, we intend to establish a normative data for overnight dexamethasone suppressed ACTH and cortisol levels in various patient groups